Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Chia-Chang; Department of Urology, Taipei Medical University—Shuang Ho Hospital, Taipei, Taiwan; Huang, Yung-Kai

2013-10-01

Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-α, IL-6 and IL-8 have been shown to be involved in the development and progression of various cancers, including bladder cancer. This study aimed to investigate the joint effect of the polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C, IL-8 − 251 T/A and urinary arsenic profiles on urothelial carcinoma (UC) risk. This study evaluated 300 pathologically-confirmed cases of UC and 594 cancer-free controls. Urinary arsenic species were detected using high-performance liquidmore » chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C and IL-8 − 251 T/A was determined using polymerase chain reaction-restriction fragment length polymorphism. The joint effects on UC risk were estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. We found that the TNF-α − 308 A/A and IL-8 − 251 T/T polymorphisms were significantly associated with UC. Moreover, significant dose–response joint effect of TNF-α − 308 A/A or IL-8 − 251 T/T genotypes and arsenic methylation indices were seen to affect UC risk. The present results also showed a significant increase in UC risk in subjects with the IL-8 − 251 T/T genotype for each SD increase in urinary total arsenic and MMA%. In contrast, a significant decrease in UC risk was found in subjects who carried the IL-8 − 251 T/T genotype for each SD increase in DMA%. - Highlights: • Joint effect of the TNF-α -308 A/A genotype and urinary total arsenic affected UC. • Joint effect of the IL-8 -251 T/T genotype and urinary total arsenic affected UC. • Urinary total arsenic level, TNF-α -308 A/A and IL-8 -251 T/T genotype affected UC.« less

Association between body mass index and arsenic methylation efficiency in adult women from southwest U.S. and northwest Mexico

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomez-Rubio, Paulina; Roberge, Jason; Arendell, Leslie

2011-04-15

Human arsenic methylation efficiency has been consistently associated with arsenic-induced disease risk. Interindividual variation in arsenic methylation profiles is commonly observed in exposed populations, and great effort has been put into the study of potential determinants of this variability. Among the factors that have been evaluated, body mass index (BMI) has not been consistently associated with arsenic methylation efficiency; however, an underrepresentation of the upper BMI distribution was commonly observed in these studies. This study investigated potential factors contributing to variations in the metabolism of arsenic, with specific interest in the effect of BMI where more than half of themore » population was overweight or obese. We studied 624 adult women exposed to arsenic in drinking water from three independent populations. Multivariate regression models showed that higher BMI, arsenic (+ 3 oxidation state) methyltransferase (AS3MT) genetic variant 7388, and higher total urinary arsenic were significantly associated with low percentage of urinary arsenic excreted as monomethylarsonic acid (%uMMA) or high ratio between urinary dimethylarsinic acid and uMMA (uDMA/uMMA), while AS3MT genetic variant M287T was associated with high %uMMA and low uDMA/uMMA. The association between BMI and arsenic methylation efficiency was also evident in each of the three populations when studied separately. This strong association observed between high BMI and low %uMMA and high uDMA/uMMA underscores the importance of BMI as a potential arsenic-associated disease risk factor, and should be carefully considered in future studies associating human arsenic metabolism and toxicity.« less

Urinary total arsenic and 8-hydroxydeoxyguanosine are associated with renal cell carcinoma in an area without obvious arsenic exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Chao-Yuan; Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan; Su, Chien-Tien

2012-08-01

8-Hydroxydeoxyguanosine (8-OHdG) is one of the most reliable and abundant markers of DNA damage. The study was designed to explore the relationship between urinary 8-OHdG and renal cell carcinoma (RCC) and to investigate whether individuals with a high level of 8-OHdG would have a modified odds ratio (OR) of arsenic-related RCC. This case–control study was conducted with 132 RCC patients and 245 age- and sex-matched controls from a hospital-based pool between November 2006 and May 2009. Pathological verification of RCC was completed by image-guided biopsy or surgical resection of renal tumors. Urinary 8-OHdG levels were determined using liquid chromatography withmore » tandem mass spectrometry (LC–MS/MS). Concentrations of urinary arsenic species, including inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Level of urinary 8-OHdG was significantly associated with the OR of RCC in a dose–response relationship after multivariate adjustment. Urinary 8-OHdG was significantly related to urinary total arsenic. The greatest OR (3.50) was seen in the individuals with high urinary 8-OHdG and high urinary total arsenic. A trend test indicated that the OR of RCC was increased with one of these factors and was further increased with both (p = 0.002). In conclusion, higher urinary 8-OHdG was a strong predictor of the RCC. High levels of 8-OHdG combined with urinary total arsenic might be indicative of arsenic-induced RCC. -- Highlights: ► Urinary 8-OHdG was significantly related to urinary total arsenic. ► Higher urinary 8-OHdG was a strong predictor of RCC risk. ► Urinary 8-OHdG may modify arsenic related RCC risk.« less

Urinary arsenic profiles reveal exposures to inorganic arsenic from private drinking water supplies in Cornwall, UK.

PubMed

Middleton, D R S; Watts, M J; Hamilton, E M; Ander, E L; Close, R M; Exley, K S; Crabbe, H; Leonardi, G S; Fletcher, T; Polya, D A

2016-05-09

Private water supplies (PWS) in Cornwall, South West England exceeded the current WHO guidance value and UK prescribed concentration or value (PCV) for arsenic of 10 μg/L in 5% of properties surveyed (n = 497). In this follow-up study, the first of its kind in the UK, volunteers (n = 207) from 127 households who used their PWS for drinking, provided urine and drinking water samples for total As determination by inductively coupled plasma mass spectrometry (ICP-MS) and urinary As speciation by high performance liquid chromatography ICP-MS (HPLC-ICP-MS). Arsenic concentrations exceeding 10 μg/L were found in the PWS of 10% of the volunteers. Unadjusted total urinary As concentrations were poorly correlated (Spearman's ρ = 0.36 (P < 0.001)) with PWS As largely due to the use of spot urine samples and the dominance of arsenobetaine (AB) from seafood sources. However, the osmolality adjusted sum, U-As(IMM), of urinary inorganic As species, arsenite (As(III)) and arsenate (As(V)), and their metabolites, methylarsonate (MA) and dimethylarsinate (DMA), was found to strongly correlate (Spearman's ρ: 0.62 (P < 0.001)) with PWS As, indicating private water supplies as the dominant source of inorganic As exposure in the study population of PWS users.

Urinary arsenic profiles reveal exposures to inorganic arsenic from private drinking water supplies in Cornwall, UK

PubMed Central

Middleton, D. R. S.; Watts, M. J.; Hamilton, E. M.; Ander, E. L.; Close, R. M.; Exley, K. S.; Crabbe, H.; Leonardi, G. S.; Fletcher, T.; Polya, D. A.

2016-01-01

Private water supplies (PWS) in Cornwall, South West England exceeded the current WHO guidance value and UK prescribed concentration or value (PCV) for arsenic of 10 μg/L in 5% of properties surveyed (n = 497). In this follow-up study, the first of its kind in the UK, volunteers (n = 207) from 127 households who used their PWS for drinking, provided urine and drinking water samples for total As determination by inductively coupled plasma mass spectrometry (ICP-MS) and urinary As speciation by high performance liquid chromatography ICP-MS (HPLC-ICP-MS). Arsenic concentrations exceeding 10 μg/L were found in the PWS of 10% of the volunteers. Unadjusted total urinary As concentrations were poorly correlated (Spearman’s ρ = 0.36 (P < 0.001)) with PWS As largely due to the use of spot urine samples and the dominance of arsenobetaine (AB) from seafood sources. However, the osmolality adjusted sum, U-AsIMM, of urinary inorganic As species, arsenite (AsIII) and arsenate (AsV), and their metabolites, methylarsonate (MA) and dimethylarsinate (DMA), was found to strongly correlate (Spearman’s ρ: 0.62 (P < 0.001)) with PWS As, indicating private water supplies as the dominant source of inorganic As exposure in the study population of PWS users. PMID:27156998

Urinary arsenic profiles reveal exposures to inorganic arsenic from private drinking water supplies in Cornwall, UK

NASA Astrophysics Data System (ADS)

Middleton, D. R. S.; Watts, M. J.; Hamilton, E. M.; Ander, E. L.; Close, R. M.; Exley, K. S.; Crabbe, H.; Leonardi, G. S.; Fletcher, T.; Polya, D. A.

2016-05-01

Private water supplies (PWS) in Cornwall, South West England exceeded the current WHO guidance value and UK prescribed concentration or value (PCV) for arsenic of 10 μg/L in 5% of properties surveyed (n = 497). In this follow-up study, the first of its kind in the UK, volunteers (n = 207) from 127 households who used their PWS for drinking, provided urine and drinking water samples for total As determination by inductively coupled plasma mass spectrometry (ICP-MS) and urinary As speciation by high performance liquid chromatography ICP-MS (HPLC-ICP-MS). Arsenic concentrations exceeding 10 μg/L were found in the PWS of 10% of the volunteers. Unadjusted total urinary As concentrations were poorly correlated (Spearman’s ρ = 0.36 (P < 0.001)) with PWS As largely due to the use of spot urine samples and the dominance of arsenobetaine (AB) from seafood sources. However, the osmolality adjusted sum, U-AsIMM, of urinary inorganic As species, arsenite (AsIII) and arsenate (AsV), and their metabolites, methylarsonate (MA) and dimethylarsinate (DMA), was found to strongly correlate (Spearman’s ρ: 0.62 (P < 0.001)) with PWS As, indicating private water supplies as the dominant source of inorganic As exposure in the study population of PWS users.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, Ya-Tang; Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan; Genomics Research Center, Academia Sinica, Taiwan

Arsenic ingestion has been linked to increasing global prevalence of and mortality from cardiovascular disease (CVD); arsenic can be removed from drinking water to reduce related health effects. Lactate dehydrogenase (LDH) is used for the evaluation of acute arsenic toxicity in vivo and in vitro, but it is not validated for the evaluation of long-term, chronic arsenic exposure. The present study examined the long-term effect of chronic arsenic exposure on CVD and serum LDH levels, after consideration of arsenic metabolism capacity. A total of 380 subjects from an arseniasis-endemic area and 303 from a non-endemic area of southwestern Taiwan weremore » recruited in 2002. Various urinary arsenic species were analyzed using high-performance liquid chromatography (HPLC) and hydride generation systems. Fasting serum was used for quantitative determination of the total LDH activity. A significant dose–response relationship was observed between arsenic exposure and LDH elevation, independent of urinary arsenic profiles (P < 0.001). Furthermore, abnormal LDH elevation was associated with CVD mortality after adjustment for Framingham risk scores for 10-year CVD and arsenic exposure (hazard ratio, 3.98; 95% confidence interval, 1.07–14.81). LDH was elevated in subjects with arsenic exposure in a dose-dependent manner. LDH is a marker of arsenic toxicity associated with CVD mortality. Results of this study have important implications for use in ascertaining long-term arsenic exposure risk of CVD. -- Highlights: ► We showed that arsenic exposure was correlated with LDH elevation. ► LDH elevation was related to arsenic methylation capacity. ► Abnormal LDH elevation can be a marker of susceptibility to CVD mortality.« less

XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiang, Chien-I; Huang, Ya-Li; Chen, Wei-Jen

The association between DNA repair gene polymorphisms and bladder cancer has been widely studied. However, few studies have examined the correlation between urothelial carcinoma (UC) and arsenic or its metabolites. The aim of this study was to examine the association between polymorphisms of the DNA repair genes, XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln, with urinary arsenic profiles and UC. To this end, we conducted a hospital-based case–control study with 324 UC patients and 647 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Glnmore » by PCR-restriction fragment length polymorphism analysis (PCR-RFLP). Urinary arsenic profiles were measured by high performance liquid chromatography (HPLC) linked with hydride generator and atomic absorption spectrometry. The XRCC1 399 Gln/Gln and 194 Arg/Trp and Trp/Trp genotypes were significantly related to UC, and the odds ratio (OR) and 95% confidence interval (95%CI) were 1.68 (1.03–2.75) and 0.66 (0.48–0.90), respectively. Participants with higher total urinary arsenic levels, a higher percentage of inorganic arsenic (InAs%) and a lower percentage of dimethylarsinic acid (DMA%) had a higher OR of UC. Participants carrying XRCC1 risk diplotypes G-C/G-C, A-C/A-C, and A-T/G-T, and who had higher total arsenic levels, higher InAs%, or lower DMA% compared to those with other XRCC1 diplotypes had a higher OR of UC. Our results suggest that the XRCC1 399 Gln/Gln and 194 Arg/Arg DNA repair genes play an important role in poor arsenic methylation capacity, thereby increasing the risk of UC in non-obvious arsenic exposure areas. - Highlights: • The XRCC1 399Gln/Gln genotype was significantly associated with increased OR of UC. • The XRCC1 194 Arg/Trp and Trp/Trp genotype had a significantly decreased OR of UC. • Combined effect of the XRCC1 genotypes and poor arsenic methylation capacity on UC.« less

COMPARISON OF THE URINARY METABOLITES OF RATS, MICE, AND HUMANS AFTER ORAL ARSENIC EXPOSURE FOCUSING ON THIOARSENICALS

EPA Science Inventory

Urinary metabolites of arsenic are useful as biomarkers of exposure because ingested arsenic is excreted primarily in urine1. Complete urinary arsenic speciation can provide insight into possible metabolic pathways as well as potential exposure sources. The pattern of excreted me...

Evaluation of urinary speciated arsenic in NHANES: Issues in interpretation in the context of potential inorganic arsenic exposure

EPA Science Inventory

Urinary dimethylarsinic acid (DMA) and monomethylarsonic acid (MMA) are among the commonly used biomarkers for inorganic arsenic (iAs) exposure, but may also arise from seafood consumption and organoarsenical pesticide applications. We examined speciated urinary arsenic data from...

GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh.

PubMed

Rodrigues, Ema G; Kile, Molly; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Hsueh, Yumei; Christiani, David C

2012-05-01

We determined whether single nucleotide polymorphisms (SNPs) in the glutathione S-transferase omega (GSTO) and arsenic(III)methyltransferase (AS3MT) genes were associated with concentrations of urinary arsenic metabolites among 900 individuals without skin lesions in Bangladesh. Four SNPs were assessed in these genes. A pathway analysis evaluated the association between urinary arsenic metabolites and SNPs. GSTO1 rs4925 homozygous wild type was significantly associated with higher monomethylarsonic acid (MMA) and dimethylarsinic acid urinary concentrations, whereas wild-type AS3MT rs11191439 had significantly lower levels of As(III) and MMA. Genetic polymorphisms GSTO and As3MT modify arsenic metabolism as evidenced by altered urinary arsenic excretion.

Urinary and dietary analysis of 18,470 bangladeshis reveal a correlation of rice consumption with arsenic exposure and toxicity.

PubMed

Melkonian, Stephanie; Argos, Maria; Hall, Megan N; Chen, Yu; Parvez, Faruque; Pierce, Brandon; Cao, Hongyuan; Aschebrook-Kilfoy, Briseis; Ahmed, Alauddin; Islam, Tariqul; Slavcovich, Vesna; Gamble, Mary; Haris, Parvez I; Graziano, Joseph H; Ahsan, Habibul

2013-01-01

We utilized data from the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, to evaluate the association of steamed rice consumption with urinary total arsenic concentration and arsenical skin lesions in the overall study cohort (N=18,470) and in a subset with available urinary arsenic metabolite data (N=4,517). General linear models with standardized beta coefficients were used to estimate associations between steamed rice consumption and urinary total arsenic concentration and urinary arsenic metabolites. Logistic regression models were used to estimate prevalence odds ratios (ORs) and their 95% confidence intervals (CIs) for the associations between rice intake and prevalent skin lesions at baseline. Discrete time hazard models were used to estimate discrete time (HRs) ratios and their 95% CIs for the associations between rice intake and incident skin lesions. Steamed rice consumption was positively associated with creatinine-adjusted urinary total arsenic (β=0.041, 95% CI: 0.032-0.051) and urinary total arsenic with statistical adjustment for creatinine in the model (β=0.043, 95% CI: 0.032-0.053). Additionally, we observed a significant trend in skin lesion prevalence (P-trend=0.007) and a moderate trend in skin lesion incidence (P-trend=0.07) associated with increased intake of steamed rice. This study suggests that rice intake may be a source of arsenic exposure beyond drinking water.

Effects of biological and behavioral factors on urinary arsenic ...

EPA Pesticide Factsheets

Abstract In older men and women who were long-term residents of Churchill County, Nevada, we examined the relation between arsenic exposure from home tap water and urinary levels of inorganic arsenic and its methylated metabolites. Over a wide exposure range (up to 1850 ug of arsenic per liter), urinary concentrations of inorganic, monomethylated, and dimethylated arsenicals strongly correlated with home tap water arsenic concentrations. However, percentages of summed urinary concentrations of inorganic, monomethylated, and dimethylated arsenicals accounted for by each arsenical species were unaffected by arsenic concentration in home tap water, suggesting thc1t capacity for formation and excretion of methylated metabolites was not exceeded. Biological factors (gender, age, body mass index, and genotype) and a behavioral factor (smoking) influenced absolute and relative levels of arsenicals in urine. A multivariate regression model showed that both biological and behavioral factors were significant predictors of absolute and relative concentrations of inorganic arsenic and its methylated metabolites in urine. These findings suggest that analyses of dose-response relations in arsenic-exposed populations should account for these biological and behavioral factors. Furthermore, evidence of significant effects of these factors on arsenic metabolism may support mode of action studies in appropriate experimental models. Running title- Methylated arsenicals as urinary b

Urinary and Dietary Analysis of 18,470 Bangladeshis Reveal a Correlation of Rice Consumption with Arsenic Exposure and Toxicity

PubMed Central

Melkonian, Stephanie; Argos, Maria; Hall, Megan N.; Chen, Yu; Parvez, Faruque; Pierce, Brandon; Cao, Hongyuan; Aschebrook-Kilfoy, Briseis; Ahmed, Alauddin; Islam, Tariqul; Slavcovich, Vesna; Gamble, Mary; Haris, Parvez I.; Graziano, Joseph H.; Ahsan, Habibul

2013-01-01

Background We utilized data from the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, to evaluate the association of steamed rice consumption with urinary total arsenic concentration and arsenical skin lesions in the overall study cohort (N=18,470) and in a subset with available urinary arsenic metabolite data (N=4,517). Methods General linear models with standardized beta coefficients were used to estimate associations between steamed rice consumption and urinary total arsenic concentration and urinary arsenic metabolites. Logistic regression models were used to estimate prevalence odds ratios (ORs) and their 95% confidence intervals (CIs) for the associations between rice intake and prevalent skin lesions at baseline. Discrete time hazard models were used to estimate discrete time (HRs) ratios and their 95% CIs for the associations between rice intake and incident skin lesions. Results Steamed rice consumption was positively associated with creatinine-adjusted urinary total arsenic (β=0.041, 95% CI: 0.032-0.051) and urinary total arsenic with statistical adjustment for creatinine in the model (β=0.043, 95% CI: 0.032-0.053). Additionally, we observed a significant trend in skin lesion prevalence (P-trend=0.007) and a moderate trend in skin lesion incidence (P-trend=0.07) associated with increased intake of steamed rice. Conclusions This study suggests that rice intake may be a source of arsenic exposure beyond drinking water. PMID:24260455

DNA repair gene XPD and susceptibility to arsenic-induced hyperkeratosis.

PubMed

Ahsan, Habibul; Chen, Yu; Wang, Qiao; Slavkovich, Vesna; Graziano, Joseph H; Santella, Regina M

2003-07-20

Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. An estimated 50-70 million people in Bangladesh have been chronically exposed to arsenic from drinking water and are at risk of skin and other cancers. We undertook the first study to examine whether genetic susceptibility, as determined by the codon 751 SNP (A-->C) of the DNA repair gene XPD, influences the risk of arsenic-induced hyperkeratotic skin lesions, precursors of skin cancer, in a case-control study of 29 hyperkeratosis cases and 105 healthy controls from the same community in an area of Bangladesh. As expected, there was a monotonic increase in risk of hyperkeratosis in relation to urinary arsenic measures but the XPD genotype was not independently associated with the risk. However, the increase in hyperkeratosis risk in relation to urinary arsenic measures genotype was borderline significant for urinary total arsenic (P for trend=0.06) and statistically significant for urinary creatinine adjusted arsenic (P for trend=0.01) among subjects with the XPD A allele (AA) but not among subjects with the other XPD genotypes. Among AA carriers, the risk for the highest arsenic exposed group compared with the lowest was more than 7-fold for urinary total arsenic and about 11-fold for urinary creatinine adjusted arsenic. In conclusion, our findings suggest that the DNA repair gene XPD may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions. Future larger studies are needed to confirm this novel finding and investigate how combinations of different candidate genes and/or other host and environmental factors may influence the risk of arsenic induced skin and other cancers.

Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenic.

PubMed Central

Farmer, J G; Johnson, L R

1990-01-01

An analytical speciation method, capable of separating inorganic arsenic (As (V), As (III] and its methylated metabolites (MMAA, DMAA) from common, inert, dietary organoarsenicals, was applied to the determination of arsenic in urine from a variety of workers occupationally exposed to inorganic arsenic compounds. Mean urinary arsenic (As (V) + As (III) + MMAA + DMAA) concentrations ranged from 4.4 micrograms/g creatinine for controls to less than 10 micrograms/g for those in the electronics industry, 47.9 micrograms/g for timber treatment workers applying arsenical wood preservatives, 79.4 micrograms/g for a group of glassworkers using arsenic trioxide, and 245 micrograms/g for chemical workers engaged in manufacturing and handling inorganic arsenicals. The maximum recorded concentration was 956 micrograms/g. For the most exposed groups, the ranges in the average urinary arsenic speciation pattern were 1-6% As (V), 11-14% As (III), 14-18% MMAA, and 63-70% DMAA. The highly raised urinary arsenic concentrations for the chemical workers, in particular, and some glassworkers are shown to correspond to possible atmospheric concentrations in the workplace and intakes in excess of, or close to, recommended and statutory limits and those associated with inorganic arsenic related diseases. PMID:2357455

Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh.

PubMed

Hata, Akihisa; Yamanaka, Kenzo; Habib, Mohamed Ahsan; Endo, Yoko; Fujitani, Noboru; Endo, Ginji

2012-05-01

Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content. The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry. The median iAs concentration in drinking water was 55 μgAs/L (range <0.5-332 μgAs/L). Speciation analysis revealed the presence of arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid in urine samples with medians (range) of 16.8 (7.7-32.3), 1.8 (<0.5-3.3), 13.7 (5.6-25.0), and 88.6 μgAs/L (47.9-153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water. All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration.

Biological and behavioral factors modify urinary arsenic metabolic profiles in a U.S. population.

PubMed

Hudgens, Edward E; Drobna, Zuzana; He, Bin; Le, X C; Styblo, Miroslav; Rogers, John; Thomas, David J

2016-05-26

Because some adverse health effects associated with chronic arsenic exposure may be mediated by methylated arsenicals, interindividual variation in capacity to convert inorganic arsenic into mono- and di-methylated metabolites may be an important determinant of risk associated with exposure to this metalloid. Hence, identifying biological and behavioral factors that modify an individual's capacity to methylate inorganic arsenic could provide insights into critical dose-response relations underlying adverse health effects. A total of 904 older adults (≥45 years old) in Churchill County, Nevada, who chronically used home tap water supplies containing up to 1850 μg of arsenic per liter provided urine and toenail samples for determination of total and speciated arsenic levels. Effects of biological factors (gender, age, body mass index) and behavioral factors (smoking, recent fish or shellfish consumption) on patterns of arsenicals in urine were evaluated with bivariate analyses and multivariate regression models. Relative contributions of inorganic, mono-, and di-methylated arsenic to total speciated arsenic in urine were unchanged over the range of concentrations of arsenic in home tap water supplies used by study participants. Gender predicted both absolute and relative amounts of arsenicals in urine. Age predicted levels of inorganic arsenic in urine and body mass index predicted relative levels of mono- and di-methylated arsenic in urine. Smoking predicted both absolute and relative levels of arsenicals in urine. Multivariate regression models were developed for both absolute and relative levels of arsenicals in urine. Concentration of arsenic in home tap water and estimated water consumption were strongly predictive of levels of arsenicals in urine as were smoking, body mass index, and gender. Relative contributions of arsenicals to urinary arsenic were not consistently predicted by concentrations of arsenic in drinking water supplies but were more consistently predicted by gender, body mass index, age, and smoking. These findings suggest that analyses of dose-response relations in arsenic-exposed populations should account for biological and behavioral factors that modify levels of inorganic and methylated arsenicals in urine. Evidence of significant effects of these factors on arsenic metabolism may also support mode of action studies in appropriate experimental models.

Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant.

PubMed Central

Yager, J W; Hicks, J B; Fabianova, E

1997-01-01

Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study ws undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites--inorganic arsenic (Asi), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)--prior to the start of each shift. Results from a small number of cascade impactor air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions >/= 3.5 micron. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 microg/m3 (range 0.17-375.2) and the mean sum of urinary arsenic (SigmaAs) metabolites was 16.9 microg As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 microg/m3 arsenic from coal fly ash, the predicted mean concentration of the SigmaAs urinary metabolites was 13.2 microg As/G creatinine [95% confidence interval (CI), 10.1-16.3). Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic. Images Figure 1. A Figure 1. B Figure 2. PMID:9347899

Arsenic exposure levels in relation to different working departments in a copper mining and smelting plant

NASA Astrophysics Data System (ADS)

Sun, Qingshan; Song, Yingli; Liu, Shengnan; Wang, Fei; Zhang, Lin; Xi, Shuhua; Sun, Guifan

2015-10-01

The investigation was carried out to evaluate arsenic exposure and the urine metabolite profiles of workers with different working departments, including administration (Group1), copper ore mining (Group2), copper ore grinding (Group3), electrolytic procession (Group4) and copper smelting (Group5) in a Copper mining and processing plant in China. Information about characteristics of each subject was obtained by questionnaire and inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) in urine were determined. The highest urinary levels of iAs, MMA and DMA all were found in the Group 5. Group 4 workers had a higher iAs% and a lower PMI compared to Group 3. The urinary total As (TAs) levels of 54.7% subjects exceeded 50 μg/g Cr, and the highest percentage (93.3%) was found in Group 5, smelters. The results of the present study indicate that workers in copper production plant indeed exposed to As, especially for smelters and workers of electrolytic process.

Correlation of arsenic exposure through drinking groundwater and urinary arsenic excretion among adults in Pakistan.

PubMed

Ahmed, Mubashir; Fatmi, Zafar; Ali, Arif

2014-01-01

Long-term exposure to arsenic has been associated with manifestation of skin lesions (melanosis/keratosis) and increased risk of internal cancers (lung/bladder). The objective of the study described here was to determine the relationship between exposure of arsenic through drinking groundwater and urinary arsenic excretion among adults > or =15 years of age living in Khairpur district, Pakistan. Total arsenic was determined in drinking groundwater and in spot urine samples of 465 randomly selected individuals through hydride generation-atomic absorption spectrometry. Spearman's rank correlation coefficient was calculated between arsenic in drinking groundwater and arsenic excreted in urine. The median arsenic concentration in drinking water was 2.1 microg/L (range: 0.1-350), and in urine was 28.5 microg/L (range: 0.1-848). Positive correlation was found between total arsenic in drinking water and in urine (r = .52, p < .01). Urinary arsenic may be used as a biomarker of arsenic exposure through drinking water.

INFLUENCE OF DIETARY ARSENIC ON URINARY ARSENIC METABOLITE EXCRETION

EPA Science Inventory

Influence of Dietary Arsenic on Urinary Arsenic Metabolite Excretion

Cara L. Carty, M.S., Edward E. Hudgens, B.Sc., Rebecca L. Calderon, Ph.D., M.S.P.H., Richard Kwok, M.S.P.H., Epidemiology and Biomarkers Branch/HSD, NHEERL/US EPA; David J. Thomas, Ph.D., Pharmacokinetics...

A COMPARISON OF URINARY ARSENIC SPECIATION VIA DIRECT NEBULIZATION AND ON-LINE PHOTOOXIDATION-HYDRIDE GENERATION WITH DETECTION BY INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

EPA Science Inventory

Arsenic speciation continues to be important in assessing human and environmental exposure risk. Urinary arsenic analysis provides information on recent arsenic exposure. In this study, two sample introduction pathways: direct nebulization (DN) and hydride generation (HG) were ut...

Correlation of Breastmilk Arsenic With Maternal, Infant Urinary Arsenic and Drinking Water Arsenic in an Arsenic Affected Area of Bangladesh

NASA Astrophysics Data System (ADS)

Alauddin, M.; Islam, M. R.; Milton, A. H.; Alauddin, S. T.; Mouly, T.; Behri, E.; Ayesha, A.; Akter, S.; Islam, M. M.

2016-12-01

About 97% of population in Bangladesh depend on groundwater as the principle source of drinking water and this water is highly contaminated with inorganic arsenic. Consumption of arsenic contaminated drinking water by pregnant women raises the prospect of early life exposure to inorganic arsenic for newborn which may be lead to adverse health effect in later life. This work was carried out in parts of Gopalganj district in Bangladesh, a region affected by arsenic contamination in groundwater. The objective of the work was to assess potential early life exposure to arsenic for infants through breastfeeding by mothers who were drinking water with arsenic levels ranging from 100 to 300 µg/l. A cohort of 30 mother-baby pairs were selected for the current study. Breastmilk samples from mothers, urine samples from each pair of subjects at 1, 6 and 9 month age of infant were collected and total arsenic were determined in these samples. In addition speciation of urinary arsenic and metabolites were carried out in 12 mother-baby pairs. Median level for breastmilk arsenic were 0.50 µg/l. Urinary arsenic of infants did not correlate with breastmilk arsenic with progressing age of infants. Maternal and infant urinary total arsenic at 1 month age of infant showed some positive correlation (r = 0.39). In infant urine major metabolite were dimethyl arsenic acid (DMA) (approximately 70%) indicating good methylating capacity for infants at 1 and 6 months of age. In conclusion, infants were not exposed to arsenic through breastfeeding even though mothers were exposed to significant levels of arsenic through drinking water.

DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMASIII AND DMASIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC

EPA Science Inventory

DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMAsIII and DMAsIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC.
L. M. Del Razo1, M. Styblo2, W. R. Cullen3, and D.J. Thomas4.
1Toxicology Section, Cinvestav-IPN, Mexico, D.F., 2Univ. North Carolina, Chapel Hill, NC; 3Uni...

Urinary arsenic levels influenced by abandoned mine tailings in the Southernmost Baja California Peninsula, Mexico.

PubMed

Colín-Torres, Carlos G; Murillo-Jiménez, Janette M; Del Razo, Luz M; Sánchez-Peña, Luz C; Becerra-Rueda, Oscar F; Marmolejo-Rodríguez, Ana J

2014-10-01

Gold has been mined at San Antonio-El Triunfo, (Baja California Sur, Mexico) since the 18th century. This area has approximately 5,700 inhabitants living in the San Juan de Los Planes and El Carrizal hydrographic basins, close to more than 100 abandoned mining sites containing tailings contaminated with potentially toxic elements such as arsenic. To evaluate the arsenic exposure of humans living in the surrounding areas, urinary arsenic species, such as inorganic arsenic (iAs) and the metabolites mono-methylated (MMA) and di-methylated arsenic acids (DMA), were evaluated in 275 residents (18-84 years of age). Arsenic species in urine were analyzed by hydride generation-cryotrapping-atomic absorption spectrometry, which excludes the non-toxic forms of arsenic such as those found in seafood. Urinary samples contained a total arsenic concentration (sum of arsenical species) which ranged from 1.3 to 398.7 ng mL(-1), indicating 33% of the inhabitants exceeded the biological exposition index (BEI = 35 ng mL(-1)), the permissible limit for occupational exposure. The mean relative urinary arsenic species were 9, 11 and 80% for iAs, MMA and DMA, respectively, in the Los Planes basin, and 17, 10 and 73%, respectively, in the El Carrizal basin. These data indicated that environmental intervention is required to address potential health issues in this area.

Association between Arsenic Exposure from Drinking Water and Longitudinal Change in Blood Pressure among HEALS Cohort Participants.

PubMed

Jiang, Jieying; Liu, Mengling; Parvez, Faruque; Wang, Binhuan; Wu, Fen; Eunus, Mahbub; Bangalore, Sripal; Newman, Jonathan D; Ahmed, Alauddin; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Levy, Diane; Slavkovich, Vesna; Argos, Maria; Scannell Bryan, Molly; Farzan, Shohreh F; Hayes, Richard B; Graziano, Joseph H; Ahsan, Habibul; Chen, Yu

2015-08-01

Cross-sectional studies have shown associations between arsenic exposure and prevalence of high blood pressure; however, studies examining the relationship of arsenic exposure with longitudinal changes in blood pressure are lacking. We evaluated associations of arsenic exposure in relation to longitudinal change in blood pressure in 10,853 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Arsenic was measured in well water and in urine samples at baseline and in urine samples every 2 years after baseline. Mixed-effect models were used to estimate the association of baseline well and urinary creatinine-adjusted arsenic with annual change in blood pressure during follow-up (median, 6.7 years). In the HEALS population, the median water arsenic concentration at baseline was 62 μg/L. Individuals in the highest quartile of baseline water arsenic or urinary creatinine-adjusted arsenic had a greater annual increase in systolic blood pressure compared with those in the reference group (β = 0.48 mmHg/year; 95% CI: 0.35, 0.61, and β = 0.43 mmHg/year; 95% CI: 0.29, 0.56 for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models. Likewise, individuals in the highest quartile of baseline arsenic exposure had a greater annual increase in diastolic blood pressure for water arsenic and urinary creatinine-adjusted arsenic, (β = 0.39 mmHg/year; 95% CI: 0.30, 0.49, and β = 0.45 mmHg/year; 95% CI: 0.36, 0.55, respectively) compared with those in the lowest quartile. Our findings suggest that long-term arsenic exposure may accelerate age-related increases in blood pressure. These findings may help explain associations between arsenic exposure and cardiovascular disease.

DNA methylation changes in Mexican children exposed to arsenic from two historic mining areas in San Luis potosí.

PubMed

Alegría-Torres, Jorge Alejandro; Carrizales-Yánez, Leticia; Díaz-Barriga, Fernando; Rosso-Camacho, Fernando; Motta, Valeria; Tarantini, Letizia; Bollati, Valentina

2016-12-01

Arsenic is a carcinogen and epimutagen that threatens the health of exposed populations worldwide. In this study, we examined the methylation status of Alu and long interspersed nucleotide elements (LINE-1) and their association with levels of urinary arsenic in 84 Mexican children between 6 and 12 years old from two historic mining areas in the State of San Luis Potosí, Mexico. Urinary arsenic levels were determined by atomic absorption spectrophotometry and DNA methylation analysis was performed in peripheral blood leukocytes by bisulfite-pyrosequencing. The geometric mean of urinary arsenic was 26.44 µg/g Cr (range 1.93-139.35). No significant differences in urinary arsenic or methylation patterns due to gender were observed. A positive correlation was found between urinary arsenic and the mean percentage of methylated cytosines in Alu sequences (Spearman correlation coefficient r = 0.532, P < 0.001), and a trend of LINE-1 hypomethylation was also observed (Spearman correlation coefficient r = -0.232, P = 0.038) after adjustment for sex and age. A linear regression model showed an association with log-normalized urinary arsenic for Alu (β = 1.05, 95% CI: 0.67; 1.43, P < 0.001) and LINE-1 (β = -0.703, 95% CI: -1.36; -0.38, P = 0.038). Despite the low-level arsenic exposure, a subtle epigenetic imbalance measured as DNA methylation was detected in the leukocytes of Mexican children living in two historic mining areas. Environ. Mol. Mutagen. 57:717-723, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Evaluation of Exposure to Arsenic in Residential Soil

PubMed Central

Tsuji, Joyce S.; Van Kerkhove, Maria D.; Kaetzel, Rhonda S.; Scrafford, Carolyn G.; Mink, Pamela J.; Barraj, Leila M.; Crecelius, Eric A.; Goodman, Michael

2005-01-01

In response to concerns regarding arsenic in soil from a pesticide manufacturing plant, we conducted a biomonitoring study on children younger than 7 years of age, the age category of children most exposed to soil. Urine samples from 77 children (47% participation rate) were analyzed for total arsenic and arsenic species related to ingestion of inorganic arsenic. Older individuals also provided urine (n = 362) and toenail (n = 67) samples. Speciated urinary arsenic levels were similar between children (geometric mean, geometric SD, and range: 4.0, 2.2, and 0.89–17.7 μg/L, respectively) and older participants (3.8, 1.9, 0.91–19.9 μg/L) and consistent with unexposed populations. Toenail samples were < 1 mg/kg. Correlations between speciated urinary arsenic and arsenic in soil (r = 0.137, p = 0.39; n = 41) or house dust (r = 0.049, p = 0.73; n = 52) were not significant for children. Similarly, questionnaire responses indicating soil exposure were not associated with increased urinary arsenic levels. Relatively low soil arsenic exposure likely precluded quantification of arsenic exposure above background. PMID:16330356

Dietary administration of sodium arsenite to rats: Relations between dose and urinary concentrations of methylated and thio-metabolites and effects on the rat urinary bladder epithelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Shugo; Arnold, Lora L.; Pennington, Karen L.

2010-04-15

Based on epidemiological data, chronic exposure to high levels of inorganic arsenic in drinking water is carcinogenic to humans, inducing skin, urinary bladder and lung tumors. In vivo, inorganic arsenic is metabolized to organic methylated arsenicals including the highly toxic dimethylarsinous acid (DMA{sup III}) and monomethylarsonous acid (MMA{sup III}). Short-term treatment of rats with 100 mug/g trivalent arsenic (As{sup III}) as sodium arsenite in the diet or in drinking water induced cytotoxicity and necrosis of the urothelial superficial layer, with increased cell proliferation and hyperplasia. The objectives of this study were to determine if these arsenic-induced urothelial effects are dosemore » responsive, the dose of arsenic at which urothelial effects are not detected, and the urinary concentrations of the arsenical metabolites. We treated female F344 rats for 5 weeks with sodium arsenite at dietary doses of 0, 1, 10, 25, 50, and 100 ppm. Cytotoxicity, cell proliferation and hyperplasia of urothelial superficial cells were increased in a dose-responsive manner, with maximum effects found at 50 ppm As{sup III}. There were no effects at 1 ppm As{sup III}. The main urinary arsenical in As{sup III}-treated rats was the organic arsenical dimethylarsinic acid (DMA{sup V}). The thio-metabolites dimethylmonothioarsinic acid (DMMTA{sup V}) and monomethylmonothioarsinic acid (MMMTA{sup V}) were also found in the urine of As{sup III}-treated rats. The LC{sub 50} concentrations of DMMTA{sup V} for rat and human urothelial cells in vitro were similar to trivalent oxygen-containing arsenicals. These data suggest that dietary As{sup III}-induced urothelial cytotoxicity and proliferation are dose responsive, and the urothelial effects have a threshold corresponding to the urinary excretion of measurable reactive metabolites.« less

Environmental arsenic exposure and serum matrix metalloproteinase-9.

PubMed

Burgess, Jefferey L; Kurzius-Spencer, Margaret; O'Rourke, Mary Kay; Littau, Sally R; Roberge, Jason; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Harris, Robin B

2013-03-01

The objective of this study was to evaluate the relationship between environmental arsenic exposure and serum matrix metalloproteinase (MMP)-9, a biomarker associated with cardiovascular disease and cancer. In a cross-sectional study of residents of Arizona, USA (n=215) and Sonora, Mexico (n=163), drinking water was assayed for total arsenic, and daily drinking water arsenic intake was estimated. Urine was speciated for arsenic, and concentrations were adjusted for specific gravity. Serum was analyzed for MMP-9 using ELISA. Mixed model linear regression was used to assess the relation among drinking water arsenic concentration, drinking water arsenic intake, urinary arsenic sum of species (the sum of arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid), and MMP-9, controlling for autocorrelation within households. Drinking water arsenic concentration and intake were positively associated with MMP-9, both in crude analysis and after adjustment for gender, country/ethnicity, age, body mass index, current smoking, and diabetes. Urinary arsenic sum of species was positively associated with MMP-9 in multivariable analysis only. Using Akaike's Information Criterion, arsenic concentration in drinking water provided a better fitting model of MMP-9 than either urinary arsenic or drinking water arsenic intake. In conclusion, arsenic exposure evaluated using all three exposure metrics was positively associated with MMP-9.

Environmental arsenic exposure and serum matrix metalloproteinase-9

PubMed Central

Burgess, Jefferey L.; Kurzius-Spencer, Margaret; O’Rourke, Mary Kay; Littau, Sally R.; Roberge, Jason; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Harris, Robin B.

2014-01-01

The objective of this study was to evaluate the relationship between environmental arsenic exposure and serum matrix metalloproteinase (MMP)-9, a biomarker associated with cardiovascular disease and cancer. In a cross-sectional study of residents of Arizona, USA (n=215) and Sonora, Mexico (n=163), drinking water was assayed for total arsenic, and daily drinking water arsenic intake estimated. Urine was speciated for arsenic and concentrations were adjusted for specific gravity. Serum was analyzed for MMP-9 using ELISA. Mixed model linear regression was used to assess the relation among drinking water arsenic concentration, drinking water arsenic intake, urinary arsenic sum of species (the sum of arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid), and MMP-9, controlling for autocorrelation within households. Drinking water arsenic concentration and intake were positively associated with MMP-9, both in crude analysis and after adjustment for gender, country/ethnicity, age, body mass index, current smoking and diabetes. Urinary arsenic sum of species was positively associated with MMP-9 in multivariable analysis only. Using Akaike’s Information Criterion, arsenic concentration in drinking water provided a better fitting model of MMP-9, than either urinary arsenic or drinking water arsenic intake. In conclusion, arsenic exposure was positively associated with MMP-9 using all three exposure metrics evaluated. PMID:23232971

Arsenic exposure and type 2 diabetes: results from the 2007-2009 Canadian Health Measures Survey.

PubMed

Feseke, S K; St-Laurent, J; Anassour-Sidi, E; Ayotte, P; Bouchard, M; Levallois, P

2015-06-01

Inorganic arsenic and its metabolites are considered dangerous to human health. Although several studies have reported associations between low-level arsenic exposure and diabetes mellitus in the United States and Mexico, this association has not been studied in the Canadian population. We evaluated the association between arsenic exposure, as measured by total arsenic concentration in urine, and the prevalence of type 2 diabetes (T2D) in 3151 adult participants in Cycle 1 (2007-2009) of the Canadian Health Measures Survey (CHMS). All participants were tested to determine blood glucose and glycated hemoglobin. Urine analysis was also performed to measure total arsenic. In addition, participants answered a detailed questionnaire about their lifestyle and medical history. We assessed the association between urinary arsenic levels and T2D and prediabetes using multivariate logistic regression while adjusting for potential confounders. Total urinary arsenic concentration was positively associated with the prevalence of T2D and prediabetes: adjusted odds ratios were 1.81 (95% CI: 1.12-2.95) and 2.04 (95% CI: 1.03-4.05), respectively, when comparing the highest (fourth) urinary arsenic concentration quartile with the lowest (first) quartile. Total urinary arsenic was also associated with glycated hemoglobin levels in people with untreated diabetes. We found significant associations between arsenic exposure and the prevalence of T2D and prediabetes in the Canadian population. Causal inference is limited due to the cross-sectional design of the study and the absence of long-term exposure assessment.

In utero and early childhood exposure to arsenic decreases lung function in children

PubMed Central

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R. Clark; Gandolfi, A. Jay; Gonzalez-De Alba, Cesar

2016-01-01

Background The lung is a target organ for adverse health outcomes following exposure to arsenic. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to arsenic through drinking water, however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of arsenic and its metabolites with lung function in children exposed in utero and in early childhood to high arsenic levels through drinking water. Methods A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic arsenic. Lung function was assessed by spirometry. Results Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 μg/L. The mean urinary arsenic level registered in the studied subjects was 141.2 μg/L and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percent of inorganic arsenic. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Conclusion Exposure to arsenic through drinking water during in utero and early life was associated with a decrease in FVC and with a restrictive spirometric pattern in the children evaluated. PMID:25131850

Associations between arsenic (+3 oxidation state) methyltransferase (AS3MT) and N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) polymorphisms, arsenic metabolism, and cancer risk in a chilean population.

PubMed

de la Rosa, Rosemarie; Steinmaus, Craig; Akers, Nicholas K; Conde, Lucia; Ferreccio, Catterina; Kalman, David; Zhang, Kevin R; Skibola, Christine F; Smith, Allan H; Zhang, Luoping; Smith, Martyn T

2017-07-01

Inter-individual differences in arsenic metabolism have been linked to arsenic-related disease risks. Arsenic (+3) methyltransferase (AS3MT) is the primary enzyme involved in arsenic metabolism, and we previously demonstrated in vitro that N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) also methylates the toxic inorganic arsenic (iAs) metabolite, monomethylarsonous acid (MMA), to the less toxic dimethylarsonic acid (DMA). Here, we evaluated whether AS3MT and N6AMT1 gene polymorphisms alter arsenic methylation and impact iAs-related cancer risks. We assessed AS3MT and N6AMT1 polymorphisms and urinary arsenic metabolites (%iAs, %MMA, %DMA) in 722 subjects from an arsenic-cancer case-control study in a uniquely exposed area in northern Chile. Polymorphisms were genotyped using a custom designed multiplex, ligation-dependent probe amplification (MLPA) assay for 6 AS3MT SNPs and 14 tag SNPs in the N6AMT1 gene. We found several AS3MT polymorphisms associated with both urinary arsenic metabolite profiles and cancer risk. For example, compared to wildtypes, individuals carrying minor alleles in AS3MT rs3740393 had lower %MMA (mean difference = -1.9%, 95% CI: -3.3, -0.4), higher %DMA (mean difference = 4.0%, 95% CI: 1.5, 6.5), and lower odds ratios for bladder (OR = 0.3; 95% CI: 0.1-0.6) and lung cancer (OR = 0.6; 95% CI: 0.2-1.1). Evidence of interaction was also observed for both lung and bladder cancer between these polymorphisms and elevated historical arsenic exposures. Clear associations were not seen for N6AMT1. These results are the first to demonstrate a direct association between AS3MT polymorphisms and arsenic-related internal cancer risk. This research could help identify subpopulations that are particularly vulnerable to arsenic-related disease. Environ. Mol. Mutagen. 58:411-422, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a Michigan population with low levels of arsenic in drinking water.

PubMed

Rivera-Núñez, Zorimar; Meliker, Jaymie R; Meeker, John D; Slotnick, Melissa J; Nriagu, Jerome O

2012-01-01

The large disparity between arsenic concentrations in drinking water and urine remains unexplained. This study aims to evaluate predictors of urinary arsenic in a population exposed to low concentrations (≤50 μg/l) of arsenic in drinking water. Urine and drinking water samples were collected from a subsample (n=343) of a population enrolled in a bladder cancer case-control study in southeastern Michigan. Total arsenic in water and arsenic species in urine were determined using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was obtained through a self-reported food intake questionnaire. Log(10)-transformed drinking water arsenic concentration at home was a significant (P<0.0001) predictor of SumAs (R(2)=0.18). Associations improved (R(2)=0.29, P<0.0001) when individuals with less than 1 μg/l of arsenic in drinking water were removed and further improved when analyses were applied to individuals who consumed amounts of home drinking water above the median volume (R(2)=0.40, P<0.0001). A separate analysis indicated that AsB and DMA[V] were significantly correlated with fish and shellfish consumption, which may suggest that seafood intake influences DMA[V] excretion. The Spearman correlation between arsenic concentration in toenails and SumAs was 0.36 and between arsenic concentration in toenails and arsenic concentration in water was 0.42. Results show that arsenic exposure from drinking water consumption is an important determinant of urinary arsenic concentrations, even in a population exposed to relatively low levels of arsenic in drinking water, and suggest that seafood intake may influence urinary DMA[V] concentrations.

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fillman, Toki, E-mail: tokif@humeco.m.u-tokyo.ac.jp; Shimizu-Furusawa, Hana, E-mail: hana-shimizu@umin.ac.jp; Ng, Chris Fook Sheng, E-mail: chrisng-tky@umin.ac.jp

Background: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. Objectives: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. Methods: Adolescents aged 12–16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction usingmore » DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. Results: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33 μg/g creatinine and 196.0±301.1 μg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (β=−0.24, 95% CI −0.42,−0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. Conclusions: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents. - Highlights: • This is the first study examining metal exposure on telomere length in adolescents. • Urinary cadmium levels were similar to non-industrially polluted levels in Asia. • Urinary arsenic levels were as high as groundwater arsenic polluted areas in Asia. • Urinary cadmium was negatively associated with salivary telomere length. • Urinary arsenic was not significantly associated with salivary telomere length.« less

A Population-based Case–Control Study of Urinary Arsenic Species and Squamous Cell Carcinoma in New Hampshire, USA

PubMed Central

Li, Zhigang; Perry, Ann E.; Spencer, Steven K.; Gandolfi, A. Jay; Karagas, Margaret R.

2013-01-01

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States. Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population. Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses. Results: In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC. Conclusions: These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association. Citation: Gilbert-Diamond D, Li Z, Perry AE, Spencer SK, Gandolfi AJ, Karagas MR. 2013. A population-based case–control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA. Environ Health Perspect 121:1154–1160; http://dx.doi.org/10.1289/ehp.1206178 PMID:23872349

Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire.

PubMed

Bommarito, Paige A; Martin, Elizabeth; Smeester, Lisa; Palys, Thomas; Baker, Emily R; Karagas, Margaret R; Fry, Rebecca C

2017-10-01

Exposure to inorganic arsenic (iAs) during pregnancy is associated with adverse health outcomes present both at birth and later in life. A biological mechanism may include epigenetic and genomic alterations in fetal genes involved in immune functioning. To investigate the role of the maternal immune response to in utero iAs exposure, we conducted an analysis of the expression of immune-related genes in pregnant women from the New Hampshire Birth Cohort Study. A set of 31 genes was identified with altered expression in association with levels of urinary total arsenic, urinary iAs, urinary monomethylated arsenic and urinary dimethylated arsenic. Notably, maternal gene expression signatures differed when stratified on fetal sex, with a more robust inflammatory response observed in male pregnancies. Moreover, the differentially expressed genes were also related to birth outcomes. These findings highlight the sex-dependent nature of the maternal iAs-induced inflammatory response in relationship to fetal outcomes. Copyright © 2017. Published by Elsevier Inc.

Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+3 oxidation state) methyltransferase knockout mice. A preliminary report

EPA Science Inventory

Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions which convert inorganic arsenic to methylated metabolites. This study determined whether the As3mt null genotype in the mouse modifies cytotoxic and proliferative effects seen in urinary bladders of wild t...

Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: Effect of sex and arsenic exposure

PubMed Central

Huang, Madelyn C.; Douillet, Christelle; Su, Mingming; Zhou, Kejun; Wu, Tao; Chen, Wenlian; Galanko, Joseph A.; Drobná, Zuzana; Saunders, R. Jesse; Martin, Elizabeth; Fry, Rebecca C.; Jia, Wei; Stýblo, Miroslav

2016-01-01

Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex-specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation. PMID:26883664

Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

PubMed

Tsinovoi, Cari L; Xun, Pengcheng; McClure, Leslie A; Carioni, Vivian M O; Brockman, John D; Cai, Jianwen; Guallar, Eliseo; Cushman, Mary; Unverzagt, Frederick W; Howard, Virginia J; He, Ka

2018-01-01

The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States. We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species. The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident. A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research. © 2017 American Heart Association, Inc.

Arsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrow

EPA Science Inventory

Arsenic is a recognized human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the urinary bladder (with cigarette smoking) and skin (with UV light exposure). Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include induction of DNA ...

HPLC-ICP-MS speciation analysis of arsenic in urine of Japanese subjects without occupational exposure.

PubMed

Hata, Akihisa; Endo, Yoko; Nakajima, Yoshiaki; Ikebe, Maiko; Ogawa, Masanori; Fujitani, Noboru; Endo, Ginji

2007-05-01

The toxicity and carcinogenicity of arsenic depend on its species. Individuals living in Japan consume much seafood that contains high levels of organoarsenics. Speciation analysis of urinary arsenic is required to clarify the health risks of arsenic intake. There has been no report of urinary arsenic analysis in Japan using high performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). We performed speciation analysis of urinary arsenic for 210 Japanese male subjects without occupational exposure using HPLC-ICP-MS. The median values of urinary arsenics were as follows: sodium arsenite (AsIII), 3.5; sodium arsenate (AsV), 0.1; monomethylarsonic acid (MMA), 3.1; dimethylarsinic acid (DMA), 42.6; arsenobetaine (AsBe), 61.3; arsenocholine, trimethylarsine oxide, and unidentified arsenics (others), 5.2; and total arsenic (total As), 141.3 microgAs/l. The median creatinine-adjusted values were as follows: AsIII, 3.0; AsV, 0.1; MMA, 2.6; DMA, 35.9; AsBe, 52.1; others 3.5; and total As, 114.9 microgAs/g creatinine. Our findings indicate that DMA and AsBe levels in Japan are much higher than those found in Italian and American studies. It appears that the high levels of DMA and AsBe observed in Japan may be due in part to seafood intake. ACGIH and DFG set the BEI and BAT values for occupational arsenic exposure as 35 microgAs/l and 50 microgAs/l, respectively, using the sum of inorganic arsenic (iAs), MMA, and DMA. In the general Japanese population, the sums of these were above 50 microgAs/l in 115 (55%) samples. We therefore recommend excluding DMA concentration in monitoring of iAs exposure.

Concentrations of urinary arsenic species in relation to rice and seafood consumption among children living in Spain.

PubMed

Signes-Pastor, Antonio J; Vioque, Jesus; Navarrete-Muñoz, Eva M; Carey, Manus; García de la Hera, Manoli; Sunyer, Jordi; Casas, Maribel; Riaño-Galán, Isolina; Tardón, Adonina; Llop, Sabrina; Amorós, Rubén; Amiano, Pilar; Bilbao, José R; Karagas, Margaret R; Meharg, Andrew A

2017-11-01

Inorganic arsenic (i-As) has been related to wide-ranging health effects in children, leading to lifelong concerns. Proportionally, dietary i-As exposure dominates in regions with low arsenic drinking water. This study aims to investigate the relation between rice and seafood consumption and urinary arsenic species during childhood and to assess the proportion of urinary i-As metabolites. Urinary arsenic species concentration in 400 4-year-old children living in four geographical areas of Spain, in addition to repeated measures from 100 children at 7 years of age are included in this study. Rice and seafood products intake was collected from children's parents using a validated food frequency questionnaire (FFQ). At 4 years of age, children's urine i-As and monomethylarsonic acid (MMA) concentrations increased with rice product consumption (p-value = 0.010 and 0.018, respectively), and urinary arsenobetaine (AsB) with seafood consumption (p = 0.002). Four-year-old children had a higher consumption of both rice and seafood per body weight and a higher urinary %MMA (p-value = 0.001) and lower % dimethylarsinic acid (DMA) (p-value = 0.017). This study suggests increased dietary i-As exposure related to rice product consumption among children living in Spain, and the younger ones may be especially vulnerable to the health impacts of this exposure also considering that they might have a lower i-As methylation capacity than older children. In contrast, seafood consumption did not appear to influence the presence of potentially toxic arsenic species in this population of children. Copyright © 2017 Elsevier Inc. All rights reserved.

Arsenic exposure and oral cavity lesions in Bangladesh.

PubMed

Syed, Emdadul H; Melkonian, Stephanie; Poudel, Krishna C; Yasuoka, Junko; Otsuka, Keiko; Ahmed, Alauddin; Islam, Tariqul; Parvez, Faruque; Slavkovich, Vesna; Graziano, Joseph H; Ahsan, Habibul; Jimba, Masamine

2013-01-01

To evaluate the relationship between arsenic exposure and oral cavity lesions among an arsenic-exposed population in Bangladesh. We carried out an analysis utilizing the baseline data of the Health Effects of Arsenic Exposure Longitudinal Study, which is an ongoing population-based cohort study to investigate health outcomes associated with arsenic exposure via drinking water in Araihazar, Bangladesh. We used multinomial regression models to estimate the risk of oral cavity lesions. Participants with high urinary arsenic levels (286.1 to 5000.0 μg/g) were more likely to develop arsenical lesions of the gums (multinomial odds ratio = 2.90; 95% confidence interval, 1.11 to 7.54), and tongue (multinomial odds ratio = 2.79; 95% confidence interval, 1.51 to 5.15), compared with those with urinary arsenic levels of 7.0 to 134.0 μg/g. Higher level of arsenic exposure was positively associated with increased arsenical lesions of the gums and tongue.

Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico.

PubMed

Meza, Maria Mercedes; Kopplin, Michael J; Burgess, Jefferey L; Gandolfi, A Jay

2004-10-01

The objective of this study was to determine arsenic exposure via drinking water and to characterize urinary arsenic excretion among adults in the Yaqui Valley, Sonora, Mexico. A cross-sectional study was conducted from July 2001 to May 2002. Study subjects were from the Yaqui Valley, Sonora, Mexico, residents of four towns with different arsenic concentrations in their drinking water. Arsenic exposure was estimated through water intake over 24 h. Arsenic excretion was assessed in the first morning void urine. Total arsenic concentrations and their species arsenate (As V), arsenite (As III), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) were determined by HPLC/ICP-MS. The town of Esperanza with the highest arsenic concentration in water had the highest daily mean intake of arsenic through drinking water, the mean value was 65.5 microg/day. Positive correlation between total arsenic intake by drinking water/day and the total arsenic concentration in urine (r = 0.50, P < 0.001) was found. Arsenic excreted in urine ranged from 18.9 to 93.8 microg/L. The people from Esperanza had the highest geometric mean value of arsenic in urine, 65.1 microg/L, and it was statistically significantly different from those of the other towns (P < 0.005). DMA was the major arsenic species in urine (47.7-67.1%), followed by inorganic arsenic (16.4-25.4%), and MMA (7.5-15%). In comparison with other reports the DMA and MMA distribution was low, 47.7-55.6% and 7.5-9.7%, respectively, in the urine from the Yaqui Valley population (except the town of Cocorit). The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations.

Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Shu-Mei

Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293more » age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR = 0.38, 95% confidence interval (CI) 0.14–0.99]. Subjects with concurrent DNMT1 rs8101626 A/A + A/G and DNMT3A rs34048824 T/T + T/C genotypes had significantly higher OR for ccRCC [OR = 2.88, 95% CI 1.44–5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 with concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan. - Highlights: • High urinary total arsenic level or polymorphism of DNMT1 increased the OR of ccRCC. • High risk genotypes of combination of DNMT1 and DNMT3A increased the OR of ccRCC. • A joint effect of urinary total arsenic level and DNMTs genotypes may affect ccRCC.« less

Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico.

PubMed

Laine, Jessica E; Bailey, Kathryn A; Rubio-Andrade, Marisela; Olshan, Andrew F; Smeester, Lisa; Drobná, Zuzana; Herring, Amy H; Stýblo, Miroslav; García-Vargas, Gonzalo G; Fry, Rebecca C

2015-02-01

Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. DW-iAs for the study subjects ranged from < 0.5 to 236 μg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization's recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations.

A population-based case-control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA.

PubMed

Gilbert-Diamond, Diane; Li, Zhigang; Perry, Ann E; Spencer, Steven K; Gandolfi, A Jay; Karagas, Margaret R

2013-10-01

Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States. We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population. We conducted a population-based case-control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses. In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC. These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association.

Arsenic Exposure From Drinking Water and the Incidence of CKD in Low to Moderate Exposed Areas of Taiwan: A 14-Year Prospective Study.

PubMed

Hsu, Ling-I; Hsieh, Fang-I; Wang, Yuan-Hung; Lai, Tai-Shuan; Wu, Meei-Maan; Chen, Chien-Jen; Chiou, Hung-Yi; Hsu, Kuang-Hung

2017-12-01

Arsenic exposure is associated with decreased kidney function. The association between low to moderate arsenic exposure and kidney disease has not been fully clarified. The association between arsenic exposure from drinking water and chronic kidney disease (CKD) was examined in a long-term prospective observational study. 6,093 participants 40 years and older were recruited from arseniasis-endemic areas in northeastern Taiwan. Arsenic levels were 28.0, 92.8, and 295.7μg/L at the 50th, 75th, and 90th percentiles, respectively. Well-water arsenic and urinary total arsenic (inorganic plus methylated arsenic species) concentrations, adjusted for urinary creatinine concentration. Kidney diseases (ICD-9 codes: 250.4, 274.1, 283.11, 403.*1, 404.*2, 404.*3, 440.1, 442.1, 447.3, or 580-589) and CKD (ICD-9 code: 585) ascertained using Taiwan's National Health Insurance database 1998 to 2011. HRs contrasting CKD risk across arsenic exposure levels were estimated using Cox regression. Prevalence ORs for proteinuria (protein excretion ≥ 200mg/g) comparing quartiles of total urinary arsenic concentrations were estimated using logistic regression. We identified 1,104 incident kidney disease cases, including 447 CKD cases (incidence rates, 166.5 and 67.4 per 10 4 person-years, respectively). A dose-dependent association between well-water arsenic concentrations and kidney diseases was observed after adjusting for age, sex, education, body mass index, cigarette smoking, alcohol consumption, and analgesic use. Using arsenic concentration ≤ 10.0μg/L as reference, multivariable-adjusted HRs for incident CKD were 1.12 (95% CI, 0.88-1.42), 1.33 (95% CI, 1.03-1.72), and 1.33 (95% CI, 1.00-1.77) for arsenic concentrations of 10.1 to 49.9, 50.0 to 149.9, and ≥150.0μg/L, respectively (P for trend=0.02). The association between arsenic concentration and kidney diseases was stronger for women (P for interaction=0.06). Arsenic values in the range of 50th to 75th and 75th to 100th percentiles of total urinary arsenic concentrations were associated with 50% and 67% higher prevalences, respectively, of proteinuria. Kidney diseases and CKD outcomes were based on diagnostic codes. Glomerular filtration rates were not available. Other heavy metals were not measured. This study describes the temporal relationship between arsenic concentrations ≥ 10μg/L in drinking water and CKD. A dose-dependent association between well-water arsenic concentration and kidney diseases was observed. Higher creatinine-adjusted urinary total arsenic concentrations were associated with a higher prevalence of proteinuria. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Total arsenic concentrations in Chinese children's urine by different geographic locations, ages, and genders.

PubMed

Zhang, Xuan; Wang, Beibei; Cui, Xiaoyong; Lin, Chunye; Liu, Xitao; Ma, Jin

2018-06-01

Little is known about the variation of Chinese children's exposure to arsenic by geography, age, gender, and other potential factors. The main objective of this study was to investigate the total arsenic concentration in Chinese children's urine by geographic locations, ages, and genders. In total, 259 24-h urine samples were collected from 210 2- to 12-year-old children in China and analyzed for total arsenic and creatinine concentrations. The results showed that the upper limit (upper limit of the 90% confidence interval for the 97.5 fractile) was 27.51 µg/L or 55.88 µg/g creatinine for Chinese children. The total urinary arsenic levels were significantly different for children in Guangdong, Hubei, and Gansu provinces (P < 0.05), where the upper limits were 24.29, 58.70, and 44.29 µg/g creatinine, respectively. In addition, the total urinary arsenic levels were higher for 2- to 7-year-old children than for 7- to 12-year-old children (P < 0.05; the upper limits were 59.06 and 44.29 µg/g creatinine, respectively) and higher for rural children than for urban children (P < 0.05; the upper limits were 59.06 and 50.44 µg/g creatinine, respectively). The total urinary arsenic levels for boys were not significantly different from those for girls (P > 0.05), although the level for boys (the upper limit was 59.30 µg/g) was slightly higher than that for girls (the upper limit was 58.64 µg/g creatinine). Because the total urinary arsenic concentrations are significantly different for general populations of children in different locations and age groups, the reference level of total urinary arsenic might be dependent on the geographic site and the child's age.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Jun; Wanibuchi, Hideki; Waalkes, Michael P.

Epidemiological studies indicated that human arsenic exposure can induce urinary bladder cancer. Methylation of inorganic arsenic can generate more reactive and toxic organic arsenical species. In this regard, it was recently reported that the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced urinary bladder tumors in rats. However, other methylated metabolites, like monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not carcinogenic to the urinary bladder. In order to compare the early effects of DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at the scanning electron microscope (SEM) level, we investigated the sub-chronic (13 weeks) toxicological effects ofmore » MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182 ppm) given in the drinking water to male and female F344 rats with a focus on the urinary bladder in this study. Obvious pathological changes, including ropy microridges, pitting, increased separation of epithelial cells, exfoliation, and necrosis, were found in the urinary bladders of both sexes, but particularly in females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic differences were found between males and females, with levels of MMA(III), a potential genotoxic form, higher in females treated with DMA(V) than in males. Thus, this study provides clear evidence that DMA(V) is more toxic to the female urinary bladder, in accord with sensitivity to carcinogenesis. Important gender-related metabolic differences including enhanced presentation of MMA(III) to the urothelial cells might possibly account for heightened sensitivity in females. However, the potential carcinogenic effects of MMA(III) need to be further elucidated.« less

Association between maternal urinary arsenic species and infant cord blood leptin levels in a New Hampshire Pregnancy Cohort.

PubMed

Gossai, Anala; Lesseur, Corina; Farzan, Shohreh; Marsit, Carmen; Karagas, Margaret R; Gilbert-Diamond, Diane

2015-01-01

Leptin is an important pleiotropic hormone involved in the regulation of nutrient intake and energy expenditure, and is known to influence body weight in infants and adults. High maternal levels of arsenic have been associated with reduced infant birth weight, but the mechanism of action is not yet understood. This study aimed to investigate the association between in utero arsenic exposure and infant cord blood leptin concentrations within 156 mother-infant pairs from the New Hampshire Birth Cohort Study (NHBCS) who were exposed to low to moderate levels of arsenic through well water and diet. In utero arsenic exposure was obtained from maternal second trimester urinary arsenic concentration, and plasma leptin levels were assessed through immunoassay. Results indicate that urinary arsenic species concentrations were predictive of infant cord blood leptin levels following adjustment for creatinine, infant birth weight for gestational age percentile, infant sex, maternal pregnancy-related weight gain, and maternal education level amongst 149 white mother-infant pairs in multivariate linear regression models. A doubling or 100% increase in total urinary arsenic concentration (iAs+MMA+DMA) was associated with a 10.3% (95% CI: 0.8-20.7%) increase in cord blood leptin levels. A 100% increase in either monomethylarsonic acid (MMA) or dimethylarsinic acid (DMA) was also associated with an 8.3% (95% CI: -1.0-18.6%) and 10.3% (95% CI: 1.2-20.2%) increase in cord blood leptin levels, respectively. The association between inorganic arsenic (iAs) and cord blood leptin was of similar magnitude and direction as other arsenic species (a 100% increase in iAs was associated with a 6.5% (95% CI: -3.4-17.5%) increase in cord blood leptin levels), albeit not significant. These results suggest in utero exposure to low levels of arsenic influences cord blood leptin concentration and presents a potential mechanism by which arsenic may impact early childhood growth. Copyright © 2014 Elsevier Inc. All rights reserved.

Oxidative DNA damage and repair in children exposed to low levels of arsenic in utero and during early childhood: Application of salivary and urinary biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinhumpatch, Pantip; Navasumrit, Panida; Chulabhorn Graduate Institute, Laksi, Bangkok

The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations withmore » other biomarkers of arsenic exposure, including arsenic accumulation in nails (r = 0.56, P < 0.001) and arsenic concentration in urine (r = 0.50, P < 0.05). Exposed children had a significant reduction in arsenic methylation capacity indicated by decreased primary methylation index and secondary methylation index in both urine and saliva samples. Levels of salivary 8-OHdG in exposed children were significantly higher (∼ 4-fold, P < 0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly lower in exposed children (∼ 3-fold, P < 0.05), suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG. Multiple regression analysis results showed that levels of inorganic arsenic (iAs) in saliva and urine had a significant positive association with salivary 8-OHdG and a significant negative association with salivary hOGG1 expression. - Highlights: • The effects of arsenic exposure in utero and through early childhood were studied. • Arsenic-exposed children had a reduction in arsenic methylation capacity. • Exposed children had more DNA damage, observed as elevated salivary 8-OHdG. • Lower salivary hOGG1 in exposed children indicated impairment of 8-OHdG repair. • Salivary and urinary 8-OHdG levels were discordant.« less

Arsenic Exposure through Drinking Water Is Associated with Longer Telomeres in Peripheral Blood

PubMed Central

2012-01-01

Inorganic arsenic is a strong carcinogen, possibly by interaction with the telomere length. The aim of the study was to evaluate how chronic arsenic exposure from drinking water as well as the arsenic metabolism efficiency affect the individual telomere length and the expression of telomere-related genes. Two hundred two women with a wide range in exposure to arsenic via drinking water (3.5–200 μg/L) were recruited. Concentrations of arsenic metabolites in urine [inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA)] were measured. The relative telomere length in blood was measured by quantitative real-time polymerase chain reaction. Genotyping (N = 172) for eight SNPs in AS3MT and gene expression of telomere-related genes (in blood; N = 90) were performed. Urinary arsenic (sum of metabolites) was positively associated with telomere length (β = 0.65 × 10–4, 95% CI = 0.031 × 10–4–1.3 × 10–4, adjusted for age and BMI). Individuals with above median fractions of iAs and MMA showed significantly longer telomeres by increasing urinary arsenic (β = 1.0 × 10–4, 95% CI = 0.21 × 10–4–1.8 × 10–4 at high % iAs; β = 0.88 × 10–4 95% CI = 0.12 × 10–4–1.6 × 10–4 at high % MMA) than those below the median (p = 0.80 and 0.44, respectively). Similarly, carriers of the slow and more toxic metabolizing AS3MT haplotype showed stronger positive associations between arsenic exposure and telomere length, as compared to noncarriers (interaction urinary arsenic and haplotype p = 0.025). Urinary arsenic was positively correlated with the expression of telomerase reverse transcriptase (TERT, Spearman r = 0.22, p = 0.037), but no association was found between TERT expression and telomere length. Arsenic in drinking water influences the telomere length, and this may be a mechanism for its carcinogenicity. A faster and less toxic arsenic metabolism diminishes arsenic-related telomere elongation. PMID:22917110

Measurements of Arsenic in the Urine and Nails of Individuals Exposed to Low Concentrations of Arsenic in Drinking Water From Private Wells in a Rural Region of Québec, Canada.

PubMed

Gagnon, Fabien; Lampron-Goulet, Eric; Normandin, Louise; Langlois, Marie-France

2016-01-01

Chronic exposure to inorganic arsenic leads to an increased risk of cancer. A biological measurement was conducted in 153 private well owners and their families consuming water contaminated by inorganic arsenic at concentrations that straddle 10 μg/L. The relationship between the external dose indicators (concentration of inorganic arsenic in wells and daily well water inorganic arsenic intake) and the internal doses (urinary arsenic--sum of As(III), DMA, and MMA, adjusted for creatinine--and total arsenic in toenails) was evaluated using multiple linear regressions, controlling for age, gender, dietary sources of arsenic, and number of cigarettes smoked. It showed that urinary arsenic was associated with concentration of inorganic arsenic in wells (p < .001) and daily well water inorganic arsenic intake (p < .001) in adults, and with daily well water inorganic arsenic intake (p = .017) and rice consumption (p = .022) in children (n = 43). The authors' study reinforces the drinking-water quality guidelines for inorganic arsenic.

Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case–control study in Michigan, USA

PubMed Central

Slotnick, Melissa J.; AvRuskin, Gillian A.; Schottenfeld, David; Jacquez, Geoffrey M.; Wilson, Mark L.; Goovaerts, Pierre; Franzblau, Alfred; Nriagu, Jerome O.

2014-01-01

Objective Arsenic in drinking water has been linked with the risk of urinary bladder cancer, but the dose–response relationships for arsenic exposures below 100 µg/L remain equivocal. We conducted a population-based case–control study in southeastern Michigan, USA, where approximately 230,000 people were exposed to arsenic concentrations between 10 and 100 µg/L. Methods This study included 411 bladder cancer cases diagnosed between 2000 and 2004, and 566 controls recruited during the same period. Individual lifetime exposure profiles were reconstructed, and residential water source histories, water consumption practices, and water arsenic measurements or modeled estimates were determined at all residences. Arsenic exposure was estimated for 99% of participants’ person-years. Results Overall, an increase in bladder cancer risk was not found for time-weighted average lifetime arsenic exposure >10 µg/L when compared with a reference group exposed to <1 µg/L (odds ratio (OR) = 1.10; 95% confidence interval (CI): 0.65, 1.86). Among ever-smokers, risks from arsenic exposure >10 µg/L were similarly not elevated when compared to the reference group (OR = 0.94; 95% CI: 0.50, 1.78). Conclusions We did not find persuasive evidence of an association between low-level arsenic exposure and bladder cancer. Selecting the appropriate exposure metric needs to be thoughtfully considered when investigating risk from low-level arsenic exposure. PMID:20084543

Strong positive associations between seafood, vegetables, and alcohol with blood mercury and urinary arsenic levels in the Korean adult population.

PubMed

Park, Sunmin; Lee, Byung-Kook

2013-01-01

Blood mercury and urinary arsenic levels are more than fivefold greater in the Korean population compared with those of the United States. This may be related to the foods people consumed. Therefore, we examined the associations between food categories and mercury and arsenic exposure in the Korean adult population. Data regarding nutritional, biochemical, and health-related parameters were obtained from a cross-sectional study, the 2008-2009 Korean National Health and Nutrition Examination Survey (3,404 men and women age ≥ 20 years). The log-transformed blood mercury and urinary arsenic levels were regressed against the frequency tertiles of each food group after covariate adjustment for sex, age, residence area, education level, smoking status, and drinking status using food-frequency data. Blood mercury levels in the high consumption groups compared to the low consumption groups were elevated by about 20 percents with salted fish, shellfish, whitefish, bluefish, and alcohol, and by about 9-14 percents with seaweeds, green vegetables, fruits and tea, whereas rice did not affect blood mercury levels. Urinary arsenic levels were markedly increased with consumption of rice, bluefish, salted fish, shellfish, whitefish, and seaweed, whereas they were moderately increased with consumption of grains, green and white vegetables, fruits, coffee, and alcohol. The remaining food categories tended to lower these levels only minimally. In conclusion, the typical Asian diet, which is high in rice, salted fish, shellfish, vegetables, alcoholic beverages, and tea, may be associated with greater blood mercury and urinary arsenic levels. This study suggests that mercury and arsenic contents should be monitored and controlled in soil and water used for agriculture to decrease health risks from heavy-metal contamination.

Maternal Arsenic Exposure, Arsenic Methylation Efficiency, and Birth Outcomes in the Biomarkers of Exposure to ARsenic (BEAR) Pregnancy Cohort in Mexico

PubMed Central

Laine, Jessica E.; Bailey, Kathryn A.; Rubio-Andrade, Marisela; Olshan, Andrew F.; Smeester, Lisa; Drobná, Zuzana; Herring, Amy H.; Stýblo, Miroslav; García-Vargas, Gonzalo G.

2014-01-01

Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. Results: DW-iAs for the study subjects ranged from < 0.5 to 236 μg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization’s recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations. Citation: Laine JE, Bailey KA, Rubio-Andrade M, Olshan AF, Smeester L, Drobná Z, Herring AH, Stýblo M, García-Vargas GG, Fry RC. 2015. Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico. Environ Health Perspect 123:186–192; http://dx.doi.org/10.1289/ehp.1307476 PMID:25325819

Urinary arsenic levels in the French adult population: the French National Nutrition and Health Study, 2006-2007.

PubMed

Saoudi, Abdessattar; Zeghnoun, Abdelkrim; Bidondo, Marie-Laure; Garnier, Robert; Cirimele, Vincent; Persoons, Renaud; Fréry, Nadine

2012-09-01

The French Nutrition and Health Survey (ENNS) was conducted to describe dietary intakes, nutritional status, physical activity, and levels of various biomarkers for environmental chemicals (heavy metals and pesticides) in the French population (adults aged 18-74 years and children aged 3-17 years living in continental France in 2006-2007). The aim of this paper was to describe the distributions of total arsenic and the sum of iAs+MMA+DMA in the general adult population, and to present their main risk factors. In the arsenic study, 1500 and 1515 adults (requested to avoid seafood intake in the previous 3 days preceding urine collection) were included respectively for the analysis of the sum of inorganic arsenic (iAs) and its two metabolites, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and for the total arsenic. Results were presented as geometric means and selected percentiles of urinary arsenic concentrations (μg/L) and creatinine-adjusted urinary arsenic (μg/g of creatinine) for total arsenic, and the sum of inorganic arsenic and metabolites (iAs+MMA+DMA). The geometric mean concentration of the sum of iAs+MMA+DMA in the adult population living in France was 3.34 μg/g of creatinine [3.23-3.45] (3.75 μg/L [3.61-3.90]) with a 95th percentile of 8.9 μg/g of creatinine (10.68 μg/L). The geometric mean concentration of total arsenic was 11.96 μg/g of creatinine [11.41-12.53] (13.42 μg/L [12.77-14.09]) with a 95th percentile of 61.29 μg/g of creatinine (72.75 μg/L). Urinary concentrations of total arsenic and iAS+MMA+DMA were influenced by sociodemographic and economic factors, and by risk factors such as consumption of seafood products and of wine. In our study, covariate-adjusted geometric means demonstrated several slight differences, due to consumption of fish, shellfish/crustaceans or wine. This study provides the first reference value for arsenic in a representative sample of the French population not particularly exposed to high levels of arsenic (10 μg/g of creatinine). It shows that urinary arsenic concentrations in the French adult population (in particular concentrations of iAs+MMA+DMA) were relatively low compared with foreign data. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel urinary biomarkers and their association with urinary heavy metals in chronic kidney disease of unknown aetiology in Sri Lanka: a pilot study

PubMed

Wanigasuriya, K; Jayawardene, I; Amarasiriwardena, C; Wickremasinghe, R

2017-12-26

Chronic kidney disease of unknown etiology (CKDu) has emerged as a significant public health problem in Sri Lanka. The role of environmental exposure to cadmium and arsenic in the aetiology of CKDu is still unclear. Identification of a panel of novel urinary biomarkers would be invaluable in the study of toxin mediated damage postulated to be the aetiology of CKDu. The aims of this study were to evaluate the profile of novel urinary biomarkers in CKDu patients and identify any association with environmental exposure to heavy metals. Thirty seven randomly selected CKDu patients attending a renal clinic in the North Central Province and two control groups namely a farmer group (n=39) and a non-farmer group (n=40) from a non-endemic area were included in this comparative cross sectional study. Urine samples were analyzed for heavy metals and five urinary biomarkers. CKDu patients had significantly elevated urinary levels of fibrinogen (198.2 ng/mg creatinine p<0.001), clusterin (3479 ng/mg creatinine p<0.001), cystatin-C (5124.8 ng/mg creatinine p<0.001) and β2-microglobulin (9913.4 ng/mg creatinine p<0.001) compared to the control groups. Fibrinogen and β2-microglobulin were the best to discriminate CKDu patients from normal individuals with the receiver operator areas under the curve being 0.867 and 0.853, respectively. Urinary fibrinogen and KIM-1 levels correlated positively with urinary arsenic levels. KIM-1 levels correlated positively with urinary mercury and lead levels but no correlation was seen with urinary cadmium levels. Fibrinogen and β2-microglobulin have the potential of being a screening tool for detection of CKDu and may aid the early diagnosis of toxin mediated tubular injury in CKDu. Their usefulness need to be further validated in a larger epidemiological study of patients with early stages of CKDu.

Effect of Dietary Treatment with Dimethylarsinous Acid (DMAIII) on the Urinary Bladder Epithelium of Arsenic (+3 Oxidation State) Methyltransferase (As3mt) Knockout and C57BL/6 Wild Type Female Mice

EPA Science Inventory

Abstract Chronic exposure to inorganic arsenic (iAs) is carcinogenic to the human urinary bladder. It produces urothelial cytotoxicity and proliferation in rats and mice. DMAv, a major methylated urinary metabolite of iAs, is a rat bladder carcinogen, but without effects on the...

Oxidative DNA damage and repair in children exposed to low levels of arsenic in utero and during early childhood: application of salivary and urinary biomarkers.

PubMed

Hinhumpatch, Pantip; Navasumrit, Panida; Chaisatra, Krittinee; Promvijit, Jeerawan; Mahidol, Chulabhorn; Ruchirawat, Mathuros

2013-12-15

The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations with other biomarkers of arsenic exposure, including arsenic accumulation in nails (r=0.56, P<0.001) and arsenic concentration in urine (r=0.50, P<0.05). Exposed children had a significant reduction in arsenic methylation capacity indicated by decreased primary methylation index and secondary methylation index in both urine and saliva samples. Levels of salivary 8-OHdG in exposed children were significantly higher (~4-fold, P<0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly lower in exposed children (~3-fold, P<0.05), suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG. Multiple regression analysis results showed that levels of inorganic arsenic (iAs) in saliva and urine had a significant positive association with salivary 8-OHdG and a significant negative association with salivary hOGG1 expression. © 2013.

PEPTIDE BINDING AS A MODE OF ACTION FOR THE CARCINOGENICITY AND TOXICITY OF ARSENIC

EPA Science Inventory

Arsenic exposure leads to tumors in human skin, lung, urinary bladder, kidney and liver. Three likely initial stages of arsenical-macromolecular interaction are (1) binding of trivalent arsenicals to the sulfhydryl groups of peptides and proteins, (2) arsenical-induced generation...

Micronucleus frequency in copper-mine workers exposed to arsenic is modulated by the AS3MT Met287Thr polymorphism.

PubMed

Hernández, Alba; Paiva, Leiliane; Creus, Amadeu; Quinteros, Domingo; Marcos, Ricard

2014-01-01

Arsenic(III)methyltransferase (AS3MT) has been demonstrated to be the key enzyme in the metabolism of arsenic as it catalyses the methylation of arsenite and monomethylarsonic acid (MMA) to form methylated arsenic species, which have higher toxic and genotoxic potential than the parent compounds. The aim of this study is to evaluate if genetic variation in the AS3MT gene influences arsenic-induced cytogenetic damage, measured by the micronucleus (MN) assay. AS3MT Met287Thr allele frequencies and MN values were determined for 207 subjects working in the copper-mine industry, who were exposed to variable levels of arsenic. The urinary arsenic profile was used as individual biomarker of arsenic exposure. Results indicate that the MN frequencies found in peripheral blood lymphocytes of the exposed population poorly correlate with the levels of total arsenic content in urine. Nevertheless, when workers were classified according to their AS3MT Met287Thr genotypes, significantly higher MN values were observed for those carrying the variant allele [odds ratio (OR), 3.4 (1.6-5.2); P=0.0003)]. To our knowledge, these results are the first to show that genetic variation in AS3MT, especially the Met287Thr polymorphism, may play a role in modulating the levels of arsenic-induced cytogenetic damage among individuals chronically exposed to arsenic. Copyright © 2013 Elsevier B.V. All rights reserved.

PROPOSED CARCINOGENIC MECHANISMS FOR ARSENIC

EPA Science Inventory

PROPOSED CARCINOGENIC MECHANISMS FOR ARSENIC.

Arsenic is a human carcinogen in skin, lung, liver, urinary bladder and kidney. In contrast,
there is no accepted experimental animal model of inorganic arsenic carcinogenesis.
Proposed mechanisms/modes of action for a...

Arsenic methylation capacity is associated with breast cancer in northern Mexico

DOE Office of Scientific and Technical Information (OSTI.GOV)

López-Carrillo, Lizbeth; Hernández-Ramírez, Raúl Ulises; Gandolfi, A. Jay

Exposure to environmental contaminants, dietary factors and lifestyles may explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs) in the drinking water is a concern in many regions, such as northern Mexico. Studies in several countries have associated the proportion of urinary monomethylarsenic (%MMA) with increased risks for many As-related diseases, including cancer. To investigate the potential relationships between the risk of BC and the capacity to methylate iAs, a hospital-based case–control study (1016 cases/1028 controls) was performed in northern Mexico. Women were directly interviewed about their reproductive histories. The profile of As metabolites in urine was determined bymore » HPLC-ICP-MS and methylation capacity was assessed by metabolite percentages and indexes. Total urinary As, excluding arsenobetaine (TAs-AsB), ranged from 0.26 to 303.29 μg/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35 μg/L). Women with higher %MMA and/or primary methylation index (PMI) had an increased BC risk (%MMA OR{sub Q5vs.Q1} = 2.63; 95%CI 1.89,3.66; p for trend < 0.001; PMI OR{sub Q5vs.Q1} = 1.90; 95%CI 1.39,2.59, p for trend < 0.001). In contrast, women with higher proportion of urinary dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC risk (%DMA OR{sub Q5vs.Q1} = 0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI OR{sub Q5vsQ1} = 0.42, 95%CI 0.31,0.59, p for trend < 0.001). Neither %iAs nor total methylation index was associated to BC risk. Inter-individual variations in iAs metabolism may play a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA and/or a lower capacity to further methylate MMA to DMA were at higher BC risk. - Highlights: • Arsenic methylation capacity is associated to an increased breast cancer (BC) risk. • Women with higher capacity to methylate arsenic to MMA were at higher BC risk. • Women with higher capacity to methylate arsenic to DMA were at lower BC risk. • Associations occurred at urinary As levels near the biological exposure index.« less

Differences in Urinary Arsenic Metabolites between Diabetic and Non-Diabetic Subjects in Bangladesh

PubMed Central

Nizam, Saika; Kato, Masashi; Yatsuya, Hiroshi; Khalequzzaman, Md.; Ohnuma, Shoko; Naito, Hisao; Nakajima, Tamie

2013-01-01

Ingestion of inorganic arsenic (iAs) is considered to be related to the development of diabetes mellitus. In order to clarify the possible differences in the metabolism in diabetics, we measured urinary iAs metabolites in diabetic cases and non-diabetic control subjects in Faridpur, an arsenic-contaminated area in Bangladesh. Physician-diagnosed type 2 diabetic cases (140 persons) and non-diabetic controls (180 persons) were recruited. Drinking water and spot urine samples were collected. Mean concentrations of total arsenic in drinking water did not differ between cases (85.1 μg/L) and controls (85.8 μg/L). The percentage of urinary iAs (iAs%) was significantly lower in cases (8.6%) than in controls (10.4%), while that of dimethylarsinic acid (DMA%) was higher in cases (82.6%) than in controls (79.9%). This may have been due to the higher secondary methylation index (SMI) in the former (11.6) rather than the latter (10.0). Adjusting for matching factors (sex and unions), and the additional other covariates (age and water arsenic) significantly attenuated the differences in iAs%, SMI, and DMA%, respectively, though the difference in monomethylarsonic acid% was newly significant in the latter adjustment. Our study did not suggest any significant differences in urinary arsenic metabolites between diabetic and non-diabetic subjects. PMID:23481591

MODES OF ACTION FOR THE CARCINOGENICITY AND TOXICITY OF ARSENIC - MOVING TOWARDS A MORE QUANTITATIVE RISK ASSESSMENT

EPA Science Inventory

Arsenic exposures can lead to human tumors in skin, lung, urinary bladder, kidney and liver. Three likely initial stages of arsenical¬macromolecular interaction are (1) binding of trivalent arsenicals to sulfhydryl groups of peptides and proteins, (2) arsenical-induced generation...

Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Victor H.

Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-{alpha}) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAs{sup III}, MAs{sup V}, DMAs{sup III}, DMAs{sup V}). This study examines the relationship between TGF-{alpha} concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) frommore » areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-{alpha} in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-{alpha} concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-{alpha} levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-{alpha} concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p < 0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-{alpha} than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p = 0.003). These results suggest that TGF-{alpha} in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas.« less

Evaluation of epigenetic alterations (mir-126 and mir-155 expression levels) in Mexican children exposed to inorganic arsenic via drinking water.

PubMed

Pérez-Vázquez, Mónica S; Ochoa-Martínez, Ángeles C; RuÍz-Vera, Tania; Araiza-Gamboa, Yesenia; Pérez-Maldonado, Iván N

2017-12-01

Recently, a great number of epidemiological studies have shown evidence that exposure to inorganic arsenic could have harmful effects on the cardiovascular system of humans. However, the underlying mechanisms through which arsenic induces cardiovascular toxic effects remain unclear. In this regard, epigenetic mechanisms have emerged as a probable connection between environment and disease phenotypes, including cardiovascular diseases. Therefore, this study aimed to evaluate epigenetic changes related to cardiotoxicity (miR-126 and miR-155 expression levels) in children from San Luis Potosi, Mexico exposed to inorganic arsenic. From 2014 to 2015, in a cross-sectional study, children (aged 6-12 years; n = 73) attending public schools at the studied sites were enrolled to take part in this study. Urinary arsenic was used as an exposure biomarker and analyzed by an atomic absorption spectrophotometry technique. On the other hand, miR-126 and miR-155 expression levels were evaluated by qRT-PCR. A mean urinary arsenic level of 30.5 ± 25.5 μg/g of creatinine was found. Moreover, the data showed a significant negative association (p < 0.05) between urinary arsenic concentrations and plasma miR-126 levels. However, an association between urinary arsenic concentrations and plasma miR-155 levels was not found (p > 0.05). In this regard, some investigations have shown an association between diminished plasma miR-126 levels and cardiovascular illnesses. The results found in this study are of concern. However, more similar studies including a larger sample size are necessary in order to clarify the real significance of the data.

A Prospective Study of Arsenic Exposure, Arsenic Methylation Capacity, and Risk of Cardiovascular Disease in Bangladesh

PubMed Central

Wu, Fen; Liu, Mengling; Parvez, Faruque; Slavkovich, Vesna; Eunus, Mahbub; Ahmed, Alauddin; Argos, Maria; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Levy, Diane; Graziano, Joseph

2013-01-01

Background: Few prospective studies have evaluated the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk. Objective: We evaluated the association of arsenic exposure from drinking water and arsenic methylation capacity with CVD risk. Method: We conducted a case–cohort study of 369 incident fatal and nonfatal cases of CVD, including 211 cases of heart disease and 148 cases of stroke, and a subcohort of 1,109 subjects randomly selected from the 11,224 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Results: The adjusted hazard ratios (aHRs) for all CVD, heart disease, and stroke in association with a 1-SD increase in baseline well-water arsenic (112 µg/L) were 1.15 (95% CI: 1.01, 1.30), 1.20 (95% CI: 1.04, 1.38), and 1.08 (95% CI: 0.90, 1.30), respectively. aHRs for the second and third tertiles of percentage urinary monomethylarsonic acid (MMA%) relative to the lowest tertile, respectively, were 1.27 (95% CI: 0.85, 1.90) and 1.55 (95% CI: 1.08, 2.23) for all CVD, and 1.65 (95% CI: 1.05, 2.60) and 1.61 (95% CI: 1.04, 2.49) for heart disease specifically. The highest versus lowest ratio of urinary dimethylarsinic acid (DMA) to MMA was associated with a significantly decreased risk of CVD (aHR = 0.54; 95% CI: 0.34, 0.85) and heart disease (aHR = 0.54; 95% CI: 0.33, 0.88). There was no significant association between arsenic metabolite indices and stroke risk. The effects of incomplete arsenic methylation capacity—indicated by higher urinary MMA% or lower urinary DMA%—with higher levels of well-water arsenic on heart disease risk were additive. There was some evidence of a synergy of incomplete methylation capacity with older age and cigarette smoking. Conclusions: Arsenic exposure from drinking water and the incomplete methylation capacity of arsenic were adversely associated with heart disease risk. PMID:23665672

Relation of dietary inorganic arsenic exposure and urinary inorganic arsenic metabolites excretion in Japanese subjects.

PubMed

Oguri, Tomoko; Yoshinaga, Jun; Suzuki, Yayoi; Tao, Hiroaki; Nakazato, Tetsuya

2017-06-03

Inorganic arsenic (InAs) is a ubiquitous metalloid that has been shown to exert multiple adverse health outcomes. Urinary InAs and its metabolite concentration has been used as a biomarker of arsenic (As) exposure in some epidemiological studies, however, quantitative relationship between daily InAs exposure and urinary InAs metabolites concentration has not been well characterized. We collected a set of 24-h duplicated diet and spot urine sample of the next morning of diet sampling from 20 male and 19 female subjects in Japan from August 2011 to October 2012. Concentrations of As species in duplicated diet and urine samples were determined by using liquid chromatography-ICP mass spectrometry with a hydride generation system. Sum of the concentrations of urinary InAs and methylarsonic acid (MMA) was used as a measure of InAs exposure. Daily dietary InAs exposure was estimated to be 0.087 µg kg -1 day -1 (Geometric mean, GM), and GM of urinary InAs+MMA concentrations was 3.5 ng mL -1 . Analysis of covariance did not find gender-difference in regression coefficients as significant (P > 0.05). Regression equation Log 10 [urinary InAs+MMA concentration] = 0.570× Log 10 [dietary InAs exposure level per body weight] + 1.15 was obtained for whole data set. This equation would be valuable in converting urinary InAs concentration to daily InAs exposure, which will be important information in risk assessment.

Estimation of Inorganic Arsenic Exposure in Populations With Frequent Seafood Intake: Evidence From MESA and NHANES

PubMed Central

Jones, Miranda R.; Tellez-Plaza, Maria; Vaidya, Dhananjay; Grau, Maria; Francesconi, Kevin A.; Goessler, Walter; Guallar, Eliseo; Post, Wendy S.; Kaufman, Joel D.; Navas-Acien, Ana

2016-01-01

The sum of urinary inorganic arsenic (iAs) and methylated arsenic (monomethylarsonate and dimethylarsinate (DMA)) species is the main biomarker of iAs exposure. Assessing iAs exposure, however, is difficult in populations with moderate-to-high seafood intakes. In the present study, we used subsamples from the Multi-Ethnic Study of Atherosclerosis (2000–2002) (n = 310) and the 2003–2006 National Health and Nutrition Examination Survey (n = 1,175). We calibrated urinary concentrations of non–seafood-derived iAs, DMA, and methylarsonate, as well as the sum of inorganic and methylated arsenic species, in the Multi-Ethnic Study of Atherosclerosis and of DMA in the National Health and Nutrition Examination Survey by regressing their original concentrations by arsenobetaine and extracting model residuals. To confirm that calibrated biomarkers reflected iAs exposure but not seafood intake, we compared urinary arsenic concentrations by levels of seafood and rice intakes. Self-reported seafood intakes, estimated n-3 polyunsaturated fatty acid levels, and measured n-3 polyunsaturated fatty acid levels were positively associated with the original urinary arsenic biomarkers. Using the calibrated arsenic biomarkers, we found a marked attenuation of the associations with self-reported seafood intake and estimated or measured n-3 fatty acids, whereas associations with self-reported rice intake remained similar. Our residual-based method provides estimates of iAs exposure and metabolism for each participant that no longer reflect seafood intake and can facilitate research about low-to-moderate levels of iAs exposure in populations with high seafood intakes. PMID:27702745

COMPARISON OF GENE EXPRESSION IN KIDNEY AND URINARY BLADDER FROM RATS TREATED WITH DIMETHYLARSINIC ACID

EPA Science Inventory

Arsenic is widespread in the environment and a human carcinogen. A major metabolite of inorganic arsenic (iAs) in most species, including humans, is dimethylarsinic acid (DMA), which is also used as a pesticide. Unlike iAs, DMA induces urinary bladder tumors in rats. DMA is belie...

THE REACTIVE OXYGEN SPECIES (ROS) THEORY OF ARSENIC CARCINOGENESIS

EPA Science Inventory

Arsenic is a human carcinogen in skin, lung, liver, urinary bladder
and kidney. At this time, there is not a scientific consensus on the
mechanisms/modes of action for arsenic carcinogenesis. Proposed
mechanisms/modes of action for arsenic carcinogenesi...

Associations between Methylated Metabolites of Arsenic and Selenium in Urine of Pregnant Bangladeshi Women and Interactions between the Main Genes Involved.

PubMed

Skröder, Helena; Engström, Karin; Kuehnelt, Doris; Kippler, Maria; Francesconi, Kevin; Nermell, Barbro; Tofail, Fahmida; Broberg, Karin; Vahter, Marie

2018-02-01

It has been proposed that interactions between selenium and arsenic in the body may affect their kinetics and toxicity. However, it is unknown how the elements influence each other in humans. We aimed to investigate potential interactions in the methylation of selenium and arsenic. Urinary selenium (U-Se) and arsenic (U-As) were measured using inductively coupled plasma mass spectrometry (ICPMS) in samples collected from pregnant women ( n =226) in rural Bangladesh at gestational weeks (GW) 8, 14, 19, and 30. Urinary concentrations of trimethyl selenonium ion (TMSe) were measured by HPLC-vapor generation-ICPMS, as were inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA). Methylation efficiency was assessed based on relative amounts (%) of arsenic and selenium metabolites in urine. Genotyping for the main arsenite and selenium methyltransferases, AS3MT and INMT, was performed using TaqMan probes or Sequenom. Multivariable-adjusted linear regression analyses indicated that %TMSe (at GW8) was positively associated with %MMA (β=1.3, 95% CI: 0.56, 2.0) and U-As, and inversely associated with %DMA and U-Se in producers of TMSe ( INMT rs6970396 AG+AA, n =74), who had a wide range of urinary TMSe (12-42%). Also, %TMSe decreased in parallel to %MMA during pregnancy, especially in the first trimester (-0.58 %TMSe per gestational week). We found a gene-gene interaction for %MMA ( p -interaction=0.076 for haplotype 1). In analysis stratified by INMT genotype, the association between %MMA and both AS3MT haplotypes 1 and 3 was stronger in women with the INMT GG (TMSe nonproducers, 5th-95th percentile: 0.2-2%TMSe) vs. AG+AA genotype. Our findings for Bangladeshi women suggest a positive association between urinary %MMA and %TMSe. Genes involved in the methylation of selenium and arsenic may interact on associations with urinary %MMA. https://doi.org/10.1289/EHP1912.

Renal, hepatic, pulmonary and adrenal tumors induced by prenatal inorganic arsenic followed by dimethylarsinic acid in adulthood in CD1 mice

PubMed Central

Tokar, Erik J.; Diwan, Bhalchandra A.; Waalkes, Michael P.

2012-01-01

Inorganic arsenic, an early life carcinogen in humans and mice, can initiate lesions promotable by other agents in later life. The biomethylation product of arsenic, dimethylarsinic acid (DMA), is a multi-site tumor promoter. Thus, pregnant CD1 mice were given drinking water (0 or 85 ppm arsenic) from gestation day 8 to 18 and after weaning male offspring received DMA (0 or 200 ppm; drinking water) for up to 2 years. No renal tumors occurred in controls or DMA alone treated mice while gestational arsenic exposure plus later DMA induced a significant renal tumor incidence of 17% (primarily renal cell carcinoma). Arsenic plus DMA or arsenic alone also increased renal hyperplasia over control but DMA alone did not. Arsenic alone, DMA alone and arsenic plus DMA all induced urinary bladder hyperplasia (33–35%) versus control (2%). Compared to control (6%), arsenic alone tripled hepatocellular carcinoma (20%), and arsenic plus DMA doubled this rate again (43%), but DMA alone had no effect. DMA alone, arsenic alone, and arsenic plus DMA increased lung adenocarcinomas and adrenal adenomas versus control. Overall, DMA in adulthood promoted tumors/lesions initiated by prenatal arsenic in the kidney and liver, but acted independently in the urinary bladder, lung and adrenal. PMID:22230260

Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic☆

PubMed Central

Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Víctor H.; Contreras-Ruiz, José; García-Vargas, Gonzalo G.; Del Razo, Luz M.

2009-01-01

Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-α) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAsIII, MAsV, DMAsIII, DMAsV). This study examines the relationship between TGF-α concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) from areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-α in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-α concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-α levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-α concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p<0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-α than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p=0.003). These results suggest that TGF-α in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas. PMID:17267001

Ground water arsenic contamination in West Bengal, India: a risk of sub-clinical toxicity in cattle as evident by correlation between arsenic exposure, excretion and deposition.

PubMed

Bera, Asit Kumar; Rana, Tanmoy; Das, Subhshree; Bhattacharya, Debasis; Bandyopadhyay, Subhasish; Pan, Diganta; De, Sumanta; Samanta, Srikanta; Chowdhury, Atalanta Narayan; Mondal, Tapan Kumar; Das, Subrata Kumar

2010-11-01

Arsenic contamination of ground water in West Bengal, India, is a great concern for both human and livestock populations. Our study investigated and correlated the arsenic concentration in the drinking water, urinary excretion and deposition of total arsenic in hair of cattle at an arsenic contaminated zone in West Bengal. The results of our study indicated that the average concentration of arsenic in tube well water in contaminated villages ranged from 0.042 to 0.251 ppm and a statistical significant (p < 0.01) difference was seen when compared to samples from a non-contaminated zone. The arsenic concentration in urine and hair of cattle ranged between 0.245-0.691 ppm and 0.461-0.984 ppm, respectively. A close relationship was found between the total arsenic in drinking water urinary excretion (r² = 0.03664, p < 0.05) and the arsenic concentration in hair (r² = 0.03668, p < 0.05). Our findings indicate that quantification of arsenic concentration in cattle urine and hair can serve as biomarkers for both present and past exposure in cattle population.

DIFFERENTIAL MODULATION OF CANCER-RELATED MOLECULAR NETWORKS IN HUMAN AND RAT URINARY BLADDER CELLS EXPOSED TO TRIVALENT ARSENICALS

EPA Science Inventory

Arsenic (As) is classified as a known human carcinogen with primary targets of urinary bladder (UB), skin and lung. The most prevalent source of As exposure in humans is drinking water contaminated with inorganic As (iAs), and millions of people worldwide are exposed to drinking ...

Investigation of Health Effects According to the Exposure of Low Concentration Arsenic Contaminated Ground Water

PubMed Central

Hong, Young-seoub; Ye, Byeong-jin; Kim, Yu-mi; Kim, Byoung-gwon; Kang, Gyeong-hui; Kim, Jeong-jin; Song, Ki-hoon; Kim, Young-hun

2017-01-01

Recent epidemiological studies have reported adverse health effects, including skin cancer, due to low concentrations of arsenic via drinking water. We conducted a study to assess whether low arsenic contaminated ground water affected health of the residents who consumed it. For precise biomonitoring results, the inorganic (trivalent arsenite (As III) and pentavalent arsenate (As V)) and organic forms (monomethylarsonate (MMA) and dimethylarsinate (DMA)) of arsenic were separately quantified by combining high-performance liquid chromatography and inductively coupled plasma mass spectroscopy from urine samples. In conclusion, urinary As III, As V, MMA, and hair arsenic concentrations were significantly higher in residents who consumed arsenic contaminated ground water than control participants who consumed tap water. But, most health screening results did not show a statistically significant difference between exposed and control subjects. We presume that the elevated arsenic concentrations may not be sufficient to cause detectable health effects. Consumption of arsenic contaminated ground water could result in elevated urinary organic and inorganic arsenic concentrations. We recommend immediate discontinuation of ground water supply in this area for the safety of the residents. PMID:29186890

Tissue-specific distributions of inorganic arsenic and its methylated metabolites, especially in cerebral cortex, cerebellum and hippocampus of mice after a single oral administration of arsenite.

PubMed

Li, Jinlong; Duan, Xiaoxu; Dong, Dandan; Zhang, Yang; Zhao, Lu; Li, Wei; Chen, Jinli; Sun, Guifan; Li, Bing

2017-09-01

Groundwater contaminated with inorganic arsenic (iAs) is the main source of human exposure to arsenic and generates a global health issue. In this study, the urinary excretion, as well as the time-course distributions of various arsenic species in murine tissues, especially in different brain regions were determined after a single oral administration of 2.5, 5, 10 and 20mg/kg sodium arsenite (NaAsO 2 ). Our data showed that the peak times of urinary, hepatic and nephritic total arsenic (TAs) were happened at about 1h, then TAs levels decreased gradually and almost could not be observed after 72h. On contrast, the time course of TAs in lung, urinary bladder and different brain regions exhibited an obvious process of accumulation and elimination,and the peak times were nearly at 6h to 9h. TAs levels of 10 and 20mg/kg NaAsO 2 groups were significantly higher than 2.5 and 5mg/kg groups, and the amounts of TAs in 5mg/kg groups were in the order of liver>lung>kidney>urinary bladder>hippocampus>cerebral cortex>cerebellum. In addition, iAs was the most abundant species in liver and kidney, while lung and urinary bladder accumulated the highest concentrations of dimethylated arsenicals (DMA). What's more, the distributions of arsenic species were not homogeneous among different brain regions, as DMA was the sole species in cerebral cortex and cerebellum, while extremely high concentrations and percentages of monomethylated arsenicals (MMA) were found in hippocampus. These results demonstrated that distributions of iAs and its methylated metabolites were tissue-specific and even not homogeneous among different brain regions, which must be considered as to the tissue- and region-specific toxicity of iAs exposure. Our results thus provide useful information for clarifying and reducing the uncertainty in the risk assessment for this metalloid. Copyright © 2016 Elsevier GmbH. All rights reserved.

ARSENIC URINARY METABOLITES: BIOMARKER STUDY

EPA Science Inventory

A population of adults and children with ranges of 10 to 300 g/l of arsenic in their drinking water will have their urine analyzed for total and speciated arsenic. A sample of 30 families will be selected based on tap water analyses for arsenic. This sample will comprise 50% adul...

IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC INDUCED BLADDER CANCER BY GENE EXPRESSION.

EPA Science Inventory

Arsenic is a human carcinogen that induces urinary bladder cancer. Several mechanisms have been proposed for arsenic-induced cancer. Although inorganic arsenic (iAs) does not induce tumors in adult rodents, dimethylarsinic acid (DMA), a major metabolite of iAs, is a rat bladder c...

PLASMID DNA DAMAGE CAUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

EPA Science Inventory

Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin.

Arsenic causes cancer in human skin, urinary bladder, lung, liver and kidney and is a significant world-wide public health problem. Although the metabolism of inorganic arsenic is ...

MEETING AT CAMBRIDGE, MA: GENE EXPRESSION IN NORMAL HUMAN KERATINOCYTES MODULATED BY TRIVALENT ARSENICALS

EPA Science Inventory

Arsenic exposure has been correlated with the development of several human cancers including those found in the skin, lung, liver, kidney and urinary bladder. Humans are generally exposed to inorganic forms of arsenic, which may be inhaled or ingested. Arsenic forms mono- and d...

MEETING AT SAN DIEGO, CA: GENE EXPRESSION IN NORMAL HUMAN KERATINOCYTES MODULATED BY TRIVALENT ARSENICALS

EPA Science Inventory

Arsenic exposure has been correlated with the development of several human cancers including those found in the skin, lung, liver, kidney and urinary bladder. Humans are generally exposed to inorganic forms of arsenic, which may be inhaled or ingested. Arsenic forms mono- and di-...

Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phookphan, Preeyaphan; Navasumrit, Panida

Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression of several genes related to inflammation, including COX2, EGR1, and SOCS3. This study aimed to investigate the effects of arsenic exposure on promoter DNA methylation and mRNA expression of these inflammatory genes (COX2, EGR1, and SOCS3), as well as the generation of 8-nitroguanine, which is a mutagenic DNA lesion involved in inflammation-related carcinogenesis. Prenatally arsenic-exposed newborns had promoter hypomethylationmore » of COX2, EGR1, and SOCS3 in cord blood lymphocytes (p < 0.01). A follow-up study in these prenatally arsenic-exposed children showed a significant hypomethylation of these genes in salivary DNA (p < 0.01). In vitro experiments confirmed that arsenite treatment at short-term high doses (10–100 μM) and long-term low doses (0.5–1 μM) in human lymphoblasts (RPMI 1788) caused promoter hypomethylation of these genes, which was in concordance with an increase in their mRNA expression. Additionally, the level of urinary 8-nitroguanine was significantly higher (p < 0.01) in exposed newborns and children, by 1.4- and 1.8-fold, respectively. Arsenic accumulation in toenails was negatively correlated with hypomethylation of these genes and positively correlated with levels of 8-nitroguanine. These results indicated that early-life exposure to arsenic causes hypomethylation of COX2, EGR1, and SOCS3, increases mRNA expression of these genes, and increases 8-nitroguanine formation. These effects may be linked to mechanisms of arsenic-induced inflammation and cancer development later in life. - Highlight: • Early-life arsenic exposure caused promoter hypomethylation of COX2, EGR1 and SOCS3. • Hypomethylation of these genes is associated with increased mRNA expression. • Arsenite treatment in vitro showed hypomethylation and increased mRNA expression. • Arsenic-exposed newborns and children had higher levels of urinary 8-nitroguanine. • Urinary 8-nitroguanine correlated with hypomethylation and mRNA expression.« less

Arsenic methylation and skin lesions in migrant and native adult women with chronic exposure to arsenic from drinking groundwater.

PubMed

Wei, Binggan; Yu, Jiangping; Yang, Linsheng; Li, Hairong; Chai, Yuanqing; Xia, Yajuan; Wu, Kegong; Gao, Jianwei; Guo, Zhiwei; Cui, Na

2017-02-01

In order to figure out the prevalence of skin lesions and methylation capacity for migrant and native adult women in an endemic area for arsenic poisoning in Inner Mongolia, China, 207 adult women were selected for study subjects. The results showed that the prevalence of skin lesions for the external group, provincial group and native group was 36.54, 26.15 and 35.56 %, respectively. The nail content of arsenic and urinary concentrations of dimethylarsenic (DMA), monomethylarsenic (MMA) and inorganic arsenic (iAs) were significantly higher in women with skin lesions than in those without skin lesions. The highest urinary concentrations of DMA, MMA and iAs were 213.93, 45.72 and 45.01 μg/L in the native group. The arsenic methylation capacity index revealed that the external group had the greatest capacity, while the native group had the lowest. The odds ratios of skin lesions in relation to arsenic metabolites and arsenic methylation capacity varied widely among the three groups. Urinary MMA and iAs concentrations were positively associated with risk of skin lesions in the three groups of adult women, while primary and secondary methylation capacities were negatively related to risk of skin lesions in native and provincial groups. The external group might be more susceptible to MMA and iAs, while the provincial and native groups were more tolerance to MMA and iAs. Lower primary and secondary arsenic methylation capacities increased the risk of skin lesions in native and provincial groups. Moreover, higher nail arsenic concentration increased the risk of skin lesions of adult women.

Blood Pressure Associated with Arsenic Methylation and Arsenic Metabolism Caused by Chronic Exposure to Arsenic in Tube Well Water.

PubMed

Wei, Bing Gan; Ye, Bi Xiong; Yu, Jiang Ping; Yang, Lin Sheng; Li, Hai Rong; Xia, Ya Juan; Wu, Ke Gong

2017-05-01

The effects of arsenic exposure from drinking water, arsenic metabolism, and arsenic methylation on blood pressure (BP) were observed in this study. The BP and arsenic species of 560 participants were determined. Logistic regression analysis was applied to estimate the odds ratios of BP associated with arsenic metabolites and arsenic methylation capability. BP was positively associated with cumulative arsenic exposure (CAE). Subjects with abnormal diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) usually had higher urinary iAs (inorganic arsenic), MMA (monomethylated arsenic), DMA (dimethylated arsenic), and TAs (total arsenic) than subjects with normal DBP, SBP, and PP. The iAs%, MMA%, and DMA% differed slightly between subjects with abnormal BP and those with normal BP. The PMI and SMI were slightly higher in subjects with abnormal PP than in those with normal PP. Our findings suggest that higher CAE may elevate BP. Males may have a higher risk of abnormal DBP, whereas females have a higher risk of abnormal SBP and PP. Higher urinary iAs may increase the risk of abnormal BP. Lower PMI may elevate the BP. However, higher SMI may increase the DBP and SBP, and lower SMI may elevate the PP. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

RECENT ADVANCES IN ARSENIC CARCINOGENESIS: MODES OF ACTION, ANIMAL MODEL SYSTEMS AND METHYLATED ARSENIC METABOLITES

EPA Science Inventory

Abstract:

Recent advances in our knowledge of arsenic carcinogenesis include the development of rat or mouse models for all human organs in which inorganic arsenic is known to cause cancer -skin, lung, urinary bladder, liver and kidney. Tumors can be produced from eit...

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

PubMed Central

Parvez, Faruque; Chen, Yu; Yunus, Mahbub; Olopade, Christopher; Segers, Stephanie; Slavkovich, Vesna; Argos, Maria; Hasan, Rabiul; Ahmed, Alauddin; Islam, Tariqul; Akter, Mahmud M.; Graziano, Joseph H.

2013-01-01

Rationale: Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. Objectives: To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. Methods: In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator–administered pulmonary function assessed during follow-up. Measurements and Main Results: For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV1 (−46.5 ml; P < 0.0005) and FVC (−53.1 ml; P < 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV1 (−48.3 ml; P < 0.005) and FVC (−55.2 ml; P < 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV1 (−74.4 ml, P < 0.01; and −116.1 ml, P < 0.05) and FVC (−72.8 ml, P = 0.02; and −146.9 ml, P = 0.004), respectively. Conclusions: This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low- to moderate-dose range. PMID:23848239

Changes in serum thioredoxin among individuals chronically exposed to arsenic in drinking water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yuanyuan; Gao, Yanhui; Zhao, Lijun

2012-02-15

It is well known that oxidative damage plays a key role in the development of chronic arsenicosis. There is a complex set of mechanisms of redox cycling in vivo to protect cells from the damage. In this study, we examined the differences in the levels of serum thioredoxin1 (TRX1) among individuals exposed to different levels of arsenic in drinking water and detected early biomarkers of arsenic poisoning before the appearance of skin lesions. A total of 157 subjects from endemic regions of China were selected and divided into arsenicosis group with skin lesions (total intake of arsenic: 8.68–45.71 mg-year) andmore » non-arsenicosis group without skin lesions, which further divided into low (0.00–1.06 mg-year), medium (1.37–3.55 mg-year), and high (4.26–48.13 mg-year) arsenic exposure groups. Concentrations of serum TRX1 were analyzed by an ELISA method. Levels of water arsenic and urinary speciated arsenics, including inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA), were determined by hydride generation atomic absorption spectrometry. Our results showed that the levels of serum TRX1 in arsenicosis patients were significantly higher than that of the subjects who were chronically exposed to arsenic, but without skin lesions. A positive correlation was seen between the levels of serum TRX1 and the total water arsenic intake or the levels of urinary arsenic species. The results of this study indicate that arsenic exposure could significantly change the levels of human serum TRX1, which can be detected before arsenic-specific dermatological symptoms occur. This study provides further evidence on revealing the mechanism of arsenic toxicity. -- Highlights: ► Three regions are selected as the areas affected by endemic arsenicosis of China. ► We first examine changes in serum TRX1 among individuals exposed to arsenic. ► A positive correlation was seen between serum TRX1 and total water arsenic intake. ► The same relationship was seen between serum TRX1 and urinary arsenic species. ► TRX as early biomarker of arsenicosis can be detected before skin lesions occur.« less

Renin–angiotensin–aldosterone system related gene polymorphisms and urinary total arsenic is related to chronic kidney disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Wei-Jen; Huang, Ya-Li; Shiue, Horng-Sheng

A recent study demonstrated that an increased risk of chronic kidney disease (CKD) was associated with high urinary total arsenic levels. However, whether genomic instability is related to CKD remains unclear. An association between CKD and genetic polymorphisms of regulation enzymes of the renin–angiotensin–aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AT1R), and aldosterone synthase (CYP11B2) has not been shown. The aim of the present study was to investigate the relationship between arsenic, genetic polymorphisms of RAAS enzymes and CKD. A total of 233 patients and 449 age- and gender-matched controls were recruitedmore » from the Taipei Medical University Hospital, Taipei Municipal Wan Fang Hospital and the Shin Kong Wu Ho-Su Memorial Hospital. Concentrations of urinary arsenic were determined by a high-performance liquid chromatography-linked hydride generator, and atomic absorption spectrometry. Polymorphisms of ACE(I/D), AGT(A[− 20]C), (T174M), (M235T), AT1R(A1166C) and CYP11B2(C[− 344]T) were examined by polymerase chain reaction and restriction fragment length polymorphism. Subjects carrying the CYP11B2 TT genotype had a higher odds ratio (OR), 1.39 (0.96–2.01), of CKD; while those with the AGT(A[− 20]C) CC genotype had an inverse OR of CKD (0.20 (0.05–0.81)), and a high-risk genotype was defined as A/A + A/C for AGT(A[− 20C]) and T/T for CYP11B2(C[− 344]T). The trend test showed a higher OR for CKD in patients who had either high urinary total arsenic levels or carried the high-risk genotype, or both, compared to patients with low urinary total arsenic levels, who carried the low-risk genotype, and could also be affected by the hypertension or diabetes status. - Highlights: • AGT(− 20 C) and CYP11B2(− 344 T) genotypes were significantly associated with CKD. • Combined effect of high-risk genotypes and high urinary total arsenic on OR of CKD. • Combined effect on the CKD was modified by the hypertension and diabetes status.« less

Association between arsenic exposure from drinking water and hematuria: Results from the Health Effects of Arsenic Longitudinal Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClintock, Tyler R.; Department of Environmental Medicine, New York University School of Medicine, New York, NY; Department of Urology, New York University School of Medicine, New York, NY

2014-04-01

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly relatedmore » to prevalence of hematuria (P-trend < 0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04–1.59), 1.41 (95% CI: 1.15–1.74), 1.46 (95% CI: 1.19–1.79), and 1.56 (95% CI: 1.27–1.91). Compared to those with relatively little absolute urinary As change during follow-up (− 10.40 to 41.17 μg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80–1.22) and 0.80 (95% CI: 0.65–0.99) for those whose urinary As decreased by > 47.49 μg/l and 10.87 to 47.49 μg/l since last visit, respectively, and 1.17 (95% CI: 0.94–1.45) and 1.36 (95% CI: 1.10–1.66) for those with between-visit increases of 10.40 to 41.17 μg/l and > 41.17 μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As. - Highlights: • Hematuria is the most common symptom of urinary tract disease. • Arsenic exposure is associated with renal dysfunction and urologic malignancy. • Water arsenic was positively associated with prevalence and incidence of hematuria. • Reduction in exposure lowered hematuria risk especially in low-to-moderate exposed. • Arsenic-related hematuria may represent nonmalignant or premalignant condition.« less

Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity.

PubMed

Jansen, Rick J; Argos, Maria; Tong, Lin; Li, Jiabei; Rakibuz-Zaman, Muhammad; Islam, Md Tariqul; Slavkovich, Vesna; Ahmed, Alauddin; Navas-Acien, Ana; Parvez, Faruque; Chen, Yu; Gamble, Mary V; Graziano, Joseph H; Pierce, Brandon L; Ahsan, Habibul

2016-02-01

Exposure to inorganic arsenic (iAs), a class I carcinogen, affects several hundred million people worldwide. Once absorbed, iAs is converted to monomethylated (MMA) and then dimethylated forms (DMA), with methylation facilitating urinary excretion. The abundance of each species in urine relative to their sum (iAs%, MMA%, and DMA%) varies across individuals, reflecting differences in arsenic metabolism capacity. The association of arsenic metabolism phenotypes with participant characteristics and arsenical skin lesions was characterized among 4,794 participants in the Health Effects of Arsenic Longitudinal Study (Araihazar, Bangladesh). Metabolism phenotypes include those obtained from principal component (PC) analysis of arsenic species. Two independent PCs were identified: PC1 appears to represent capacity to produce DMA (second methylation step), and PC2 appears to represent capacity to convert iAs to MMA (first methylation step). PC1 was positively associated (P <0.05) with age, female sex, and BMI, while negatively associated with smoking, arsenic exposure, education, and land ownership. PC2 was positively associated with age and education but negatively associated with female sex and BMI. PC2 was positively associated with skin lesion status, while PC1 was not. 10q24.32/AS3MT region polymorphisms were strongly associated with PC1, but not PC2. Patterns of association for most variables were similar for PC1 and DMA%, and for PC2 and MMA% with the exception of arsenic exposure and SNP associations. Two distinct arsenic metabolism phenotypes show unique associations with age, sex, BMI, 10q24.32 polymorphisms, and skin lesions. This work enhances our understanding of arsenic metabolism kinetics and toxicity risk profiles. ©2015 American Association for Cancer Research.

COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (IAS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV) AND ARSENITE (ASIII)

EPA Science Inventory

COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV) AND ARSENITE (AsIII). E M Kenyon, L M Del Razo and M F Hughes. U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; ...

Associations of arsenic metabolites, methylation capacity, and skin lesions caused by chronic exposure to high arsenic in tube well water.

PubMed

Yang, Linsheng; Chai, Yuanqing; Yu, Jiangping; Wei, Binggan; Xia, Yajuan; Wu, Kegong; Gao, Jianwei; Guo, Zhiwei; Cui, Na

2017-01-01

To investigate the interaction between skin lesion status and arsenic methylation profiles, the concentrations and proportions of arsenic metabolites in urine and arsenic methylation capacities of study subjects were determined. The results showed that the mean urinary concentrations of iAs (inorganic arsenic), MMA (monomethylarsonic acid), DMA (dimethylarsinic acid), and TAs (total arsenic) were 75.65, 68.78, 265.81, and 410.24 μg/L, respectively, in the skin lesions subjects. The highest values were observed in the multiple skin lesions subjects. Higher %iAs and %MMA, and lower %DMA, PMI (primary methylation index), and SMI (secondary methylation index) were found in skin lesions subjects. The multiple skin lesions subjects had highest %iAs and %MMA, and lowest %DMA, PMI, and SMI. The prevalence of skin lesions strongly, positively correlated with arsenic levels in drinking water. The elder persons also had higher frequency of skin lesions compared with younger persons. It can be concluded that arsenic levels in drinking water significantly affected the prevalence of skin lesions. Male subjects usually had higher proportions of skin lesions when compared with female subjects. Moreover, it may be concluded that MMA was significantly related to single skin lesion, whereas DMA and iAs were associated with multiple skin lesions. It seemed that MMA had greater toxicity to hyperkeratosis, whereas DMA and iAs had higher toxicity to depigmentation or pigmentation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 28-36, 2017. © 2015 Wiley Periodicals, Inc.

A STUDY OF THE INTERCONVERSION OF METHYLATED ARSENIC OXIDES TO METHYLATED ARSENIC SULFIDES IN SOLUTIONS CONTAINING FREE SULFIDE

EPA Science Inventory

Evidence suggests that thiolated arsenicals are urinary metabolites in both humans and rats. These thiolated species may be formed in the digestive system or as metabolites within the body. The role they may play in the overall toxicity of arsenic is an active area of research....

Arsenic Metabolism in Children Differs From That in Adults

PubMed Central

Skröder Löveborn, Helena; Lu, Ying; Ahmed, Sultan; Kuehnelt, Doris; Raqib, Rubhana; Vahter, Marie

2016-01-01

Arsenic toxicity in adults is associated with methylation efficiency, influenced by factors such as gender, genetics, and nutrition. The aim of this study was to evaluate influencing factors for arsenic metabolism in children. For 488 children (9 years), whose mothers participated in a study on arsenic exposure during pregnancy (nested into the MINIMat trial) in rural Bangladesh, we measured urinary concentrations of inorganic arsenic (iAs) and its metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by HPLC-HG-ICPMS. Methylation efficiency was assessed by relative amounts (%) of the metabolites. We evaluated the impact of factors such as maternal urinary metabolite pattern, arsenic exposure, gender, socioeconomic status, season of sampling, and nutritional factors, including erythrocyte selenium (Ery-Se), and plasma folate and vitamin B12. Children had higher %DMA and lower %iAs in urine compared to their mothers, unrelated to their lower exposure [median urinary arsenic (U-As) 53 vs 78 µg/l]. Surprisingly, selenium status (Ery-Se) was strongly associated with children’s arsenic methylation; an increase in Ery-Se from the 5–95th percentile was associated with: +1.8 percentage points (pp) for %iAs (P  =  .001), +1.4 pp for %MMA (P  =  .003), and −3.2 pp for %DMA (P  <  .001). Despite this, Ery-Se was positively associated with U-As (5–95th percentile: +41 µg/l, P  =  .026). As expected, plasma folate was inversely associated with %iAs (5–95th percentile: −1.9 pp, P  =  .001) and positively associated with %DMA (5–95th percentile: +2.2 pp, P  =  .008). Children methylated arsenic more efficiently than their mothers. Also influencing factors, mainly selenium and folate, differed. This warrants further research. PMID:27056082

AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility.

PubMed

Antonelli, Ray; Shao, Kan; Thomas, David J; Sams, Reeder; Cowden, John

2014-07-01

Oral exposure to inorganic arsenic (iAs) is associated with adverse health effects. Epidemiological studies suggest differences in susceptibility to these health effects, possibly due to genotypic variation. Genetic polymorphisms in iAs metabolism could lead to increased susceptibility by altering urinary iAs metabolite concentrations. To examine the impact of genotypic polymorphisms on iAs metabolism. We screened 360 publications from PubMed and Web of Science for data on urinary mono- and dimethylated arsenic (MMA and DMA) percentages and polymorphic genes encoding proteins that are hypothesized to play roles in arsenic metabolism. The genes we examined were arsenic (+3) methyltransferase (AS3MT), glutathione-s-transferase omega (GSTO), and purine nucleoside phosphorylase (PNP). Relevant data were pooled to determine which polymorphisms are associated across studies with changes in urinary metabolite concentration. In our review, AS3MT polymorphisms rs3740390, rs11191439, and rs11191453 were associated with statistically significant changes in percent urinary MMA. Studies of GSTO polymorphisms did not indicate statistically significant associations with methylation, and there are insufficient data on PNP polymorphisms to evaluate their impact on metabolism. Collectively, these data support the hypothesis that AS3MT polymorphisms alter in vivo metabolite concentrations. Preliminary evidence suggests that AS3MT genetic polymorphisms may impact disease susceptibility. GSTO polymorphisms were not associated with iAs-associated health outcomes. Additional data are needed to evaluate the association between PNP polymorphisms and iAs-associated health outcomes. Delineation of these relationships may inform iAs mode(s) of action and the approach for evaluating low-dose health effects for iAs. Genotype impacts urinary iAs metabolite concentrations and may be a potential mechanism for iAs-related disease susceptibility. Published by Elsevier Inc.

Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima–media thickness in Bangladesh

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Fen; Department of Environmental Medicine, New York University School of Medicine, New York, NY; Jasmine, Farzana

Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima–media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenicmore » in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = − 5.1 μm, 95% CI = − 31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = − 3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings. - Highlights: • Nine SNPs had a nominally significant interaction with well-water arsenic in cIMT. • Three SNPs in AS3MT showed nominally significant interactions with urinary arsenic. • cIMT was much higher among subjects with higher arsenic exposure and AS3MT SNPs. • The at-risk genotypes of AS3MT SNPs were positively related to urinary MMA%.« less

Proteomic Analysis of Arsenic-Induced Oxidative Stress in Human Epidermal Keratinocytes

EPA Science Inventory

Chronic exposure to inorganic arsenic (IAs) has been associated with the development of several human cancers, including those found in the skin, lung, urinary bladder, liver, prostate and kidney. The precise mechanisms by which arsenic causes cancer are unknown. Defining the mod...

Arsenic Methylation, Oxidative Stress and Cancer - Is there a Link?

EPA Science Inventory

Arsenic is a multiorgan human carcinogen. The best-known example of this effect occurred in subgroups of the Taiwanese population who were chronically exposed to high levels of naturally occurring arsenic in drinking water and developed cancers of the skin, lung, urinary bladde...

Individual variability in the human metabolism of an arsenic-containing carbohydrate, 2',3'-dihydroxypropyl 5-deoxy-5-dimethylarsinoyl-beta-D-riboside, a naturally occurring arsenical in seafood.

PubMed

Raml, Reingard; Raber, Georg; Rumpler, Alice; Bauernhofer, Thomas; Goessler, Walter; Francesconi, Kevin A

2009-09-01

We report studies on the variability in human metabolism of an oxo-arsenosugar involving the ingestion of a chemically synthesized arsenosugar and quantitative determination of the arsenic metabolites in urine and serum by HPLC coupled with arsenic-selective mass spectrometric detection (ICPMS, inductively coupled plasma mass spectrometry). The total, four-day, urinary excretion of arsenic for six volunteers ranged widely from ca. 4-95%. The arsenic metabolites present in the urine also showed great variability: high arsenic excretion was accompanied by almost complete biotransformation of the ingested oxo-arsenosugar into a multitude of metabolites (>10), whereas the subjects that excreted low amounts of arsenic produced low quantities of metabolites relative to unchanged oxo-arsenosugar and its thio-analogue. Major arsenic urinary metabolites were dimethylarsinate (DMA) and possible intermediates in the degradation of arsenosugar to DMA, namely, dimethylarsinoylethanol (DMAE) and dimethylarsinoylacetate (DMAA) present both as their oxo- and thio-analogues. Thio-DMAE and thio-DMAA were also found in blood serum indicating that these species were formed in the liver rather than on storage of the urine in the bladder. The large variability in the way individuals metabolize arsenosugars has implications for risk assessment of arsenic intake from seafood.

DIMETHYLARSINIC ACID ALTERS EXPRESSION OF OXIDATIVE STRESS AND DNA REPAIR GENES IN A DOSE DEPENDENT MANNER IN THE TRANSITIONAL EPITHELIUM OF THE URINARY BLADDER FROM FEMALE F344 RATS.

EPA Science Inventory

Dose-dependent alteration of oxidative stress and DNA repair gene expression by Dimethylarsinic acid [DMA(V)] in transitional epithelium of urinary bladder from female F344 rats.
Arsenic (As) is a major concern as millions of people are at risk from drinking arsenic contaminat...

Tissue, Dosimetry, Metabolism and Excretion of Pentavalent and Trivalent Dimethylated Arsenic in Mice after Oral Administration

EPA Science Inventory

Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of administered inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic inmice after acute oral administration. Adult fema...

Environmental exposure to arsenic, AS3MT polymorphism and prevalence of diabetes in Mexico

PubMed Central

Drobná, Zuzana; Del Razo, Luz M.; García-Vargas, Gonzalo G.; Sánchez-Peña, Luz C.; Barrera-Hernández, Angel; Stýblo, Miroslav; Loomis, Dana

2014-01-01

Exposure to arsenic in drinking water is associated with increased prevalence of diabetes. We previously reported an association of diabetes and urinary concentration of dimethylarsinite (DMAsIII), a toxic product of arsenic methylation by arsenic ( +3 oxidation state) methyltransferase (AS3MT). Here we examine associations between AS3MT polymorphism, arsenic metabolism and diabetes. Fasting blood glucose, oral glucose tolerance and self-reported diagnoses were used to identify diabetic individuals. Inorganic arsenic and its metabolites were measured in urine. Genotyping analysis focused on six polymorphic sites of AS3MT. Individuals with M287T and G4965C polymorphisms had higher levels of urinary DMAsIII and were more frequently diabetic than the respective wild-type carriers, although the excess was not statistically significant. Odds ratios were 11.4 (95% confidence interval (CI) 2.2–58.8) and 8.8 (95% CI 1.6–47.3) for the combined effects of arsenic exposure >75th percentile and 287T and 4965C genotypes, respectively. Carriers of 287T and 4965C may produce more DMAsIII and be more likely to develop diabetes when exposed to arsenic. PMID:23093101

Gene-Specific Differential DNA Methylation and Chronic Arsenic Exposure in an Epigenome-Wide Association Study of Adults in Bangladesh

PubMed Central

Argos, Maria; Chen, Lin; Jasmine, Farzana; Tong, Lin; Pierce, Brandon L.; Roy, Shantanu; Paul-Brutus, Rachelle; Gamble, Mary V.; Harper, Kristin N.; Parvez, Faruque; Rahman, Mahfuzar; Rakibuz-Zaman, Muhammad; Slavkovich, Vesna; Baron, John A.; Graziano, Joseph H.; Kibriya, Muhammad G.

2014-01-01

Background: Inorganic arsenic is one of the most common naturally occurring contaminants found in the environment. Arsenic is associated with a number of health outcomes, with epigenetic modification suggested as a potential mechanism of toxicity. Objective: Among a sample of 400 adult participants, we evaluated the association between arsenic exposure, as measured by blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation. Methods: We used linear regression models to examine the associations between arsenic exposure and methylation at each CpG site, adjusted for sex, age, and batch. Differentially methylated loci were subsequently examined in relation to corresponding gene expression for functional evidence of gene regulation. Results: In adjusted analyses, we observed four differentially methylated CpG sites with urinary total arsenic concentration and three differentially methylated CpG sites with blood arsenic concentration, based on the Bonferroni-corrected significance threshold of p < 1 × 10–7. Methylation of PLA2G2C (probe cg04605617) was the most significantly associated locus in relation to both urinary (p = 3.40 × 10–11) and blood arsenic concentrations (p = 1.48 × 10–11). Three additional novel methylation loci—SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg13651690)—were also significantly associated with arsenic exposure. Further, there was evidence of methylation-related gene regulation based on gene expression for a subset of differentially methylated loci. Conclusions: We observed significant associations between arsenic exposure and gene-specific differential white blood cell DNA methylation, suggesting that epigenetic modifications may be an important pathway underlying arsenic toxicity. The specific differentially methylated loci identified may inform potential pathways for future interventions. Citation: Argos M, Chen L, Jasmine F, Tong L, Pierce BL, Roy S, Paul-Brutus R, Gamble MV, Harper KN, Parvez F, Rahman M, Rakibuz-Zaman M, Slavkovich V, Baron JA, Graziano JH, Kibriya MG, Ahsan H. 2015. Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh. Environ Health Perspect 123:64–71; http://dx.doi.org/10.1289/ehp.1307884 PMID:25325195

Association between arsenic exposure from a coal-burning power plant and urinary arsenic concentrations in Prievidza District, Slovakia.

PubMed

Ranft, Ulrich; Miskovic, Peter; Pesch, Beate; Jakubis, Pavel; Fabianova, Elenora; Keegan, Tom; Hergemöller, Andre; Jakubis, Marian; Nieuwenhuijsen, Mark J

2003-06-01

To assess the arsenic exposure of a population living in the vicinity of a coal-burning power plant with high arsenic emission in the Prievidza District, Slovakia, 548 spot urine samples were speciated for inorganic As (Asinorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (Assum). The urine samples were collected from the population of a case-control study on nonmelanoma skin cancer (NMSC). A total of 411 samples with complete As speciations and sufficient urine quality and without fish consumption were used for statistical analysis. Although current environmental As exposure and urinary As concentrations were low (median As in soil within 5 km distance to the power plant, 41 micro g/g; median urinary Assum, 5.8 microg/L), there was a significant but weak association between As in soil and urinary Assum(r = 0.21, p < 0.01). We performed a multivariate regression analysis to calculate adjusted regression coefficients for environmental As exposure and other determinants of urinary As. Persons living in the vicinity of the plant had 27% higher Assum values (p < 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p < 0.001). NMSC cases had significantly higher levels of Assum, DMA, and Asinorg. The methylation index Asinorg/(MMA + DMA) was about 20% lower among cases (p < 0.05) and in men (p < 0.05) compared with controls and females, respectively.

Association between arsenic exposure from a coal-burning power plant and urinary arsenic concentrations in Prievidza District, Slovakia.

PubMed Central

Ranft, Ulrich; Miskovic, Peter; Pesch, Beate; Jakubis, Pavel; Fabianova, Elenora; Keegan, Tom; Hergemöller, Andre; Jakubis, Marian; Nieuwenhuijsen, Mark J

2003-01-01

To assess the arsenic exposure of a population living in the vicinity of a coal-burning power plant with high arsenic emission in the Prievidza District, Slovakia, 548 spot urine samples were speciated for inorganic As (Asinorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (Assum). The urine samples were collected from the population of a case-control study on nonmelanoma skin cancer (NMSC). A total of 411 samples with complete As speciations and sufficient urine quality and without fish consumption were used for statistical analysis. Although current environmental As exposure and urinary As concentrations were low (median As in soil within 5 km distance to the power plant, 41 micro g/g; median urinary Assum, 5.8 microg/L), there was a significant but weak association between As in soil and urinary Assum(r = 0.21, p < 0.01). We performed a multivariate regression analysis to calculate adjusted regression coefficients for environmental As exposure and other determinants of urinary As. Persons living in the vicinity of the plant had 27% higher Assum values (p < 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p < 0.001). NMSC cases had significantly higher levels of Assum, DMA, and Asinorg. The methylation index Asinorg/(MMA + DMA) was about 20% lower among cases (p < 0.05) and in men (p < 0.05) compared with controls and females, respectively. PMID:12782488

A Potential Synergy between Incomplete Arsenic Methylation Capacity and Demographic Characteristics on the Risk of Hypertension: Findings from a Cross-Sectional Study in an Arsenic-Endemic Area of Inner Mongolia, China

PubMed Central

Li, Yongfang; Wang, Da; Li, Xin; Zheng, Quanmei; Sun, Guifan

2015-01-01

Inefficient arsenic methylation capacity has been associated with various health hazards induced by arsenic. In this study, we aimed to explore the interaction effect of lower arsenic methylation capacity with demographic characteristics on hypertension risk. A total of 512 adult participants (126 hypertension subjects and 386 non-hypertension subjects) residing in an arsenic-endemic area in Inner Mongolia, China were included. Urinary levels of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured for all subjects. The percentage of urinary arsenic metabolites (iAs%, MMA%, and DMA%), primary methylation index (PMI) and secondary methylation index (SMI) were calculated to assess arsenic methylation capacity of individuals. Results showed that participants carrying a lower methylation capacity, which is characterized by lower DMA% and SMI, have a higher risk of hypertension compared to their corresponding references after adjusting for multiple confounders. A potential synergy between poor arsenic methylation capacity (higher MMA%, lower DMA% and SMI) and older age or higher BMI were detected. The joint effects of higher MMA% and lower SMI with cigarette smoking also suggest some evidence of synergism. The findings of present study indicated that inefficient arsenic methylation capacity was associated with hypertension and the effect might be enhanced by certain demographic factors. PMID:25837203

Association Between Arsenic Exposure From Drinking Water and Plasma Levels of Cardiovascular Markers

PubMed Central

Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G.; Liu, Mengling; Wójcik, Oktawia; Parvez, Faruque; Rahaman, Ronald; Roy, Shantanu; Paul-Brutus, Rachelle; Segers, Stephanie; Slavkovich, Vesna; Islam, Tariqul; Levy, Diane; Mey, Jacob L.; van Geen, Alexander; Graziano, Joseph H.; Ahsan, Habibul; Chen, Yu

2012-01-01

The authors conducted a cross-sectional study to assess the relation between arsenic exposure from drinking water and plasma levels of markers of systemic inflammation and endothelial dysfunction (matrix metalloproteinase-9, myeloperoxidase, plasminogen activator inhibitor-1, soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular adhesion molecule-1 (VCAM-1)) using baseline data from 668 participants (age, >30 years) in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2007–2008). Both well water arsenic and urinary arsenic were positively associated with plasma levels of soluble VCAM-1. For every 1-unit increase in log-transformed well water arsenic (ln μg/L) and urinary arsenic (ln μg/g creatinine), plasma soluble VCAM-1 was 1.02 (95% confidence interval: 1.01, 1.03) and 1.04 (95% confidence interval: 1.01, 1.07) times greater, respectively. There was a significant interaction between arsenic exposure and higher body mass index, such that the increased levels of plasminogen activator inhibitor-1 and soluble VCAM-1 associated with arsenic exposure were stronger among people with higher body mass index. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation and endothelial dysfunction that could be modified by body mass index and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease. PMID:22534204

Association between arsenic exposure from drinking water and plasma levels of cardiovascular markers.

PubMed

Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G; Liu, Mengling; Wójcik, Oktawia; Parvez, Faruque; Rahaman, Ronald; Roy, Shantanu; Paul-Brutus, Rachelle; Segers, Stephanie; Slavkovich, Vesna; Islam, Tariqul; Levy, Diane; Mey, Jacob L; van Geen, Alexander; Graziano, Joseph H; Ahsan, Habibul; Chen, Yu

2012-06-15

The authors conducted a cross-sectional study to assess the relation between arsenic exposure from drinking water and plasma levels of markers of systemic inflammation and endothelial dysfunction (matrix metalloproteinase-9, myeloperoxidase, plasminogen activator inhibitor-1, soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular adhesion molecule-1 (VCAM-1)) using baseline data from 668 participants (age, >30 years) in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2007-2008). Both well water arsenic and urinary arsenic were positively associated with plasma levels of soluble VCAM-1. For every 1-unit increase in log-transformed well water arsenic (ln μg/L) and urinary arsenic (ln μg/g creatinine), plasma soluble VCAM-1 was 1.02 (95% confidence interval: 1.01, 1.03) and 1.04 (95% confidence interval: 1.01, 1.07) times greater, respectively. There was a significant interaction between arsenic exposure and higher body mass index, such that the increased levels of plasminogen activator inhibitor-1 and soluble VCAM-1 associated with arsenic exposure were stronger among people with higher body mass index. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation and endothelial dysfunction that could be modified by body mass index and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.

TISSUE DOSIMETRY, METABOLISM AND EXCRETION OF PENTAVALENT AND TRIVALENT DIMETHYLATED ARSENIC IN MICE AFTER ORAL ADMINISTRATION

EPA Science Inventory

Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic in mice after acute oral administration. Adult female mice were...

Trends in urinary arsenic among the U.S. population by drinking water source: Results from the National Health and Nutritional Examinations Survey 2003-2014.

PubMed

Welch, Barrett; Smit, Ellen; Cardenas, Andres; Hystad, Perry; Kile, Molly L

2018-04-01

In 2001, the United States revised the arsenic maximum contaminant level for public drinking water systems from 50µg/L to 10µg/L. This study aimed to examine temporal trends in urinary arsenic concentrations in the U.S. population from 2003 to 2014 by drinking water source among individuals aged 12 years and older who had no detectable arsenobetaine - a biomarker of arsenic exposure from seafood intake. We examined data from 6 consecutive cycles of the National Health and Nutrition Examination Survey (2003-2014; N=5848). Total urinary arsenic (TUA) was calculated by subtracting arsenobetaine's limit of detection and detectable arsenocholine from total arsenic. Additional sensitivity analyses were conducted using a second total urinary arsenic index (TUA2, calculated by adding arsenite, arsenate, monomethylarsonic acid, dimethylarsinic acid). We classified drinking water source using 24-h dietary questionnaire data as community supply (n=3427), well or rain cistern (n=506), and did not drink tap water (n=1060). Geometric means (GM) of survey cycles were calculated from multivariate regression models adjusting for age, gender, race/ethnicity, BMI, income, creatinine, water source, type of water consumed, recent smoking, and consumption of seafood, rice, poultry, and juice. Compared to 2003-2004, adjusted TUA was 35.5% lower in 2013-2014 among the general U.S. Stratified analysis by smoking status indicated that the trend in lower TUA was only consistent among non-smokers. Compared to 2003-2004, lower adjusted TUA was observed in 2013-2014 among non-smoking participants who used community water supplies (1.98 vs 1.16µg/L, p<0.001), well or rain cistern users (1.54 vs 1.28µg/L, p<0.001) and who did not drink tap water (2.24 vs 1.53µg/L, p<0.001). Sensitivity analyses showed consistent results for participants who used a community water supplier and to a lesser extent those who did not drink tap water. However, the sensitivity analysis showed overall exposure stayed the same or was higher among well or rain cistern users. Finally, the greatest decrease in TUA was among participants within the highest exposure percentiles (e.g. 95th percentile had 34% lower TUA in 2013/2014 vs 2003/2004, p<0.001). Overall, urinary arsenic levels in the U.S. population declined over a 12-year period that encompassed the adoption of the revised Arsenic Rule. The most consistent trends in declining exposure were observed among non-smoking individuals using public community water systems. These results suggest regulation and prevention strategies to reduce arsenic exposures in the U.S. may be succeeding. Copyright © 2017 Elsevier Inc. All rights reserved.

Arsenic levels in the groundwater of Korea and the urinary excretion among contaminated area.

PubMed

Park, Jung-Duck; Choi, Seong-Jin; Choi, Byung-Sun; Lee, Choong-Ryeol; Kim, Heon; Kim, Yong-Dae; Park, Kyung-Soo; Lee, Young-Jo; Kang, Seojin; Lim, Kyung-Min; Chung, Jin-Ho

2016-09-01

Drinking water is a main source of human exposure to arsenic. Hence, the determination of arsenic in groundwater is essential to assess its impact on public health. Here, we report arsenic levels in the groundwater of 722 sites covering all six major provinces of Korea. Water was sampled in two occasions (summer, 722 sites and winter, 636 sites) and the arsenic levels were measured with highly sensitive inductively coupled plasma-mass spectrometry method (limit of detection, 0.1 μg/l) to encompass the current drinking water standard (<10 μg/l). Seasonal variation was negligible, but the geographical difference was prominent. Total arsenic in groundwater ranged from 0.1 to 48.4 μg/l. A 88.0-89.0% of sites were <2.0 μg/l and the remaining ones generally did not exceed 10 μg/l (6.4-7.0%, 2.0-4.9 μg/l; 2.4-3.0%, 5.0-9.9 μg/l). However, some areas (1.0-9.2%) exhibited >10 μg/l. Notably, urinary arsenic excretion of people around these regions was markedly higher compared with non-contaminated areas (<5 μg/l) (79.7±5.2 μg/g (N=122) vs 68.4±5.4 μg/g (N=65) creatinine, P=0.052). All stratified analysis also revealed higher urinary excretion, where a statistically significant difference was noted for non-smokers (85.9±12.7 vs 54.0±6.3, P=0.030), suggesting that arsenic-contaminated groundwater may contribute to its systemic exposure.

Preliminary analysis of in utero low-level arsenic exposure and fetal growth using biometric measurements extracted from fetal ultrasound reports.

PubMed

Davis, Matthew A; Higgins, John; Li, Zhigang; Gilbert-Diamond, Diane; Baker, Emily R; Das, Amar; Karagas, Margaret R

2015-03-30

Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value < 0.05). Although, associations were attenuated in adjusted analyses - among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: -0.151, 0.007) decrease in biparietal head diameter Z-score. Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation.

Urinary arsenic, pesticides, heavy metals, phthalates, polyaromatic hydrocarbons, and polyfluoroalkyl compounds are associated with sleep troubles in adults: USA NHANES, 2005-2006.

PubMed

Shiue, Ivy

2017-01-01

Links between environmental chemicals and human health have emerged, but the effects on sleep health were less studied. Therefore, the aim of the present study was to investigate the relationships of different sets of environmental chemicals and common sleep troubles in a national and population-based setting. Data were retrieved from the United States National Health and Nutrition Examination Surveys, 2005-2006 including demographics, serum measurements, lifestyle factors, self-reported sleep troubles, and urinary environmental chemical concentrations. Statistical analyses including descriptive statistics, t-test, chi-square test, and survey-weighted logistic regression models were performed. Of all 5563 Americans aged 18-85, 2331 (42.0%) had wake-up at night, 2914 (52.5%) felt unrested during the day, 740 (13.4%) had leg jerks while sleeping, and 1059 (19.1%) had leg cramps for 2+ times a month. Higher levels of urinary arsenic, phthalates, and polyfluoroalkyl compounds were associated with wake-up at night. Higher levels of urinary 4-tert-octylphenol and polyfluoroalkyl compounds were associated with being unrested during the day. Higher levels of urinary arsenic, polyaromatic hydrocarbons, and polyfluoroalkyl compounds were associated with leg jerks while sleeping. Higher levels of urinary pesticides, heavy metals, phthalates, and polyaromatic hydrocarbons were associated with leg cramps while sleeping. However, there were no significant associations with other environmental chemicals such as parabens, bisphenol A, benzophenone-3, triclosan, perchlorate, nitrate, or thiocyanate. Eliminating arsenic, heavy metals, phthalate, pesticides, polyaromatic hydrocarbons, and polyfluoroalkyl compounds to improve sleep health might be considered while understanding the biological pathway with a longitudinal or experimental approach in future research would be suggested.

Differences of urinary arsenic metabolites and methylation capacity between individuals with and without skin lesions in Inner Mongolia, Northern China.

PubMed

Zhang, Qiang; Li, Yongfang; Liu, Juan; Wang, Da; Zheng, Quanmei; Sun, Guifan

2014-07-18

Incomplete arsenic (As) methylation has been considered a risk factor of As-related diseases. This study aimed to examine the difference of urinary As metabolites and the methylation capacity between subjects with and without skin lesions. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analyzed. The percentage of each As species (iAs%, MMA%, and DMA%), the primary methylation index (PMI) and secondary methylation index (SMI) were calculated. The results showed that subjects with skin lesions have higher levels of urinary iAs (99.08 vs. 70.63 μg/g Cr, p = 0.006) and MMA (69.34 vs. 42.85 μg/g Cr, p = 0.016) than subjects without skin lesions after adjustment for several confounders. Significant differences of urianry MMA% (15.49 vs. 12.11, p = 0.036) and SMI (0.74 vs. 0.81, p = 0.025) were found between the two groups. The findings of the present study suggest that subjects with skin lesions may have a lower As methylation capacity than subjects without skin lesions.

Elevated childhood exposure to arsenic despite reduced drinking water concentrations--A longitudinal cohort study in rural Bangladesh.

PubMed

Kippler, Maria; Skröder, Helena; Rahman, Syed Moshfiqur; Tofail, Fahmida; Vahter, Marie

2016-01-01

The aim of this study was to evaluate the massive efforts to lower water arsenic concentrations in Bangladesh. In our large mother-child cohort in rural Matlab, we measured the arsenic concentrations (and other elements) in drinking water and evaluated the actual exposure (urinary arsenic), from early gestation to 10 years of age (n=1017). Median drinking water arsenic decreased from 23 (2002-2003) to <2 μg/L (2013), and the fraction of wells exceeding the national standard (50 μg/L) decreased from 58 to 27%. Still, some children had higher water arsenic at 10 years than earlier. Installation of deeper wells (>50 m) explained much of the lower water arsenic concentrations, but increased the manganese concentrations. The highest manganese concentrations (~900 μg/L) appeared in 50-100 m wells. Low arsenic and manganese concentrations (17% of the children) occurred mainly in >100 m wells. The decrease in urinary arsenic concentrations over time was less apparent, from 82 to 58 μg/L, indicating remaining sources of exposure, probably through food (mean 133 μg/kg in rice). Despite decreased water arsenic concentrations in rural Bangladesh, the children still have elevated exposure, largely from food. Considering the known risks of severe health effects in children, additional mitigation strategies are needed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Changes in serum thioredoxin among individuals chronically exposed to arsenic in drinking water.

PubMed

Li, Yuanyuan; Gao, Yanhui; Zhao, Lijun; Wei, Yudan; Feng, Hongqi; Wang, Cheng; Wei, Wei; Ding, Yunpeng; Sun, Dianjun

2012-02-15

It is well known that oxidative damage plays a key role in the development of chronic arsenicosis. There is a complex set of mechanisms of redox cycling in vivo to protect cells from the damage. In this study, we examined the differences in the levels of serum thioredoxin1 (TRX1) among individuals exposed to different levels of arsenic in drinking water and detected early biomarkers of arsenic poisoning before the appearance of skin lesions. A total of 157 subjects from endemic regions of China were selected and divided into arsenicosis group with skin lesions (total intake of arsenic: 8.68-45.71mg-year) and non-arsenicosis group without skin lesions, which further divided into low (0.00-1.06mg-year), medium (1.37-3.55mg-year), and high (4.26-48.13mg-year) arsenic exposure groups. Concentrations of serum TRX1 were analyzed by an ELISA method. Levels of water arsenic and urinary speciated arsenics, including inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA), were determined by hydride generation atomic absorption spectrometry. Our results showed that the levels of serum TRX1 in arsenicosis patients were significantly higher than that of the subjects who were chronically exposed to arsenic, but without skin lesions. A positive correlation was seen between the levels of serum TRX1 and the total water arsenic intake or the levels of urinary arsenic species. The results of this study indicate that arsenic exposure could significantly change the levels of human serum TRX1, which can be detected before arsenic-specific dermatological symptoms occur. This study provides further evidence on revealing the mechanism of arsenic toxicity. Copyright © 2011 Elsevier Inc. All rights reserved.

Transcriptional Modulation of the ERK1/2 MAPK and NF-kB pathways in Human Urothelial cells after trivalent arsenical exposure: Implications for urinary bladder cancer

EPA Science Inventory

Chronic exposure to drinking water contaminated with inorganic arsenic (iAs) is associated with an increased risk ofurinary bladder (DB) cancers in humans. Rodent models administered particular arsenicals have indicated urothelial necrosis followed by regenerative proliferation i...

EXCRETION OF ARSENIC IN URINE AS A FUNCTION OF EXPOSURE TO ARSENIC IN DRINKING WATER

EPA Science Inventory

Urinary arsenic (As) concentrations were evaluated as a biomarker of exposure in a U.S. population chronically exposed to inorganic As (InAs) in their drinking water. Ninety-six individuals who consumed drinking water with As concentrations of 8-620 microg/L provided first mornin...

Chronic early childhood exposure to arsenic is associated with a TNF-mediated proteomic signaling response.

PubMed

Smeester, Lisa; Bommarito, Paige A; Martin, Elizabeth M; Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Fry, Rebecca C

2017-06-01

Exposure to inorganic arsenic (iAs) in drinking water is a global public health concern and is associated with a range of health outcomes, including immune dysfunction. Children are a particularly sensitive population to the effects of inorganic arsenic, yet the biological mechanisms underlying adverse health outcomes are understudied. Here we used a proteomic approach to examine the effects of iAs exposure on circulating serum protein levels in a cross-sectional children's cohort in Mexico. To identify iAs-associated proteins, levels of total urinary arsenic (U-tAs) and its metabolites were determined and serum proteins assessed for differences in expression. The results indicate an enrichment of Tumor Necrosis Factor-(TNF)-regulated immune and inflammatory response proteins that displayed decreased expression levels in relation to increasing U-tAs. Notably, when analyzed in the context of the proportions of urinary arsenic metabolites in children, the most robust response was observed in relation to the monomethylated arsenicals. This study is among the first serum proteomics assessment in children exposed to iAs. Copyright © 2017 Elsevier B.V. All rights reserved.

Arsenic Metabolism in Children Differs From That in Adults.

PubMed

Skröder Löveborn, Helena; Kippler, Maria; Lu, Ying; Ahmed, Sultan; Kuehnelt, Doris; Raqib, Rubhana; Vahter, Marie

2016-07-01

Arsenic toxicity in adults is associated with methylation efficiency, influenced by factors such as gender, genetics, and nutrition. The aim of this study was to evaluate influencing factors for arsenic metabolism in children. For 488 children (9 years), whose mothers participated in a study on arsenic exposure during pregnancy (nested into the MINIMat trial) in rural Bangladesh, we measured urinary concentrations of inorganic arsenic (iAs) and its metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by HPLC-HG-ICPMS. Methylation efficiency was assessed by relative amounts (%) of the metabolites. We evaluated the impact of factors such as maternal urinary metabolite pattern, arsenic exposure, gender, socioeconomic status, season of sampling, and nutritional factors, including erythrocyte selenium (Ery-Se), and plasma folate and vitamin B12.Children had higher %DMA and lower %iAs in urine compared to their mothers, unrelated to their lower exposure [median urinary arsenic (U-As) 53 vs 78 µg/l]. Surprisingly, selenium status (Ery-Se) was strongly associated with children's arsenic methylation; an increase in Ery-Se from the 5-95th percentile was associated with: +1.8 percentage points (pp) for %iAs (P  =  .001), +1.4 pp for %MMA (P  =  .003), and -3.2 pp for %DMA (P  <  .001). Despite this, Ery-Se was positively associated with U-As (5-95th percentile: +41 µg/l, P  =  .026). As expected, plasma folate was inversely associated with %iAs (5-95th percentile: -1.9 pp, P  =  .001) and positively associated with %DMA (5-95th percentile: +2.2 pp, P  =  .008). Children methylated arsenic more efficiently than their mothers. Also influencing factors, mainly selenium and folate, differed. This warrants further research. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Inverse association between toenail arsenic and body mass index in a population of welders.

PubMed

Grashow, Rachel; Zhang, Jinming; Fang, Shona C; Weisskopf, Marc G; Christiani, David C; Kile, Molly L; Cavallari, Jennifer M

2014-05-01

Recent data show that arsenic may play a role in obesity-related diseases. However, urinary arsenic studies report an inverse association between arsenic level and body mass index (BMI). We explored whether toenail arsenic, a long-term exposure measure, was associated with BMI in 74 welders with known arsenic exposure. BMI showed significant inverse associations with toenail arsenic (p=0.01), which persisted in models adjusted for demographics, diet and work history. It is unclear whether low arsenic biomarker concentrations in high BMI subjects truly reflect lower exposures, or instead reflect internal or metabolic changes that alter arsenic metabolism and tissue deposition. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of Sodium Arsenite Dose Administered in the Drinking Water on the Urinary Bladder Epithelium of Female Arsenic (+3 oxidation state) Methyltransferase Knockout Mice

EPA Science Inventory

The enzyme arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions converting inorganic arsenic to methylated metabolites, some of which are highly cytotoxic. In a previous study, we evaluated whether the As3mt null genotype in mice modified cytotoxic and proli...

Dimethylarsinic acid in drinking water changed the morphology but not the expression of DNA repair genes of bladder transitional epithelium in F344 rats

EPA Science Inventory

Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In laboratory animals, it is dimethylarsinic acid [DMA(V)], a major arsenic metabolite in the urine of inorganic arsenic-exposed people, that increases transitional cell carcinoma, namely in F344 r...

The impact of a rice based diet on urinary arsenic.

PubMed

Cascio, Claudia; Raab, Andrea; Jenkins, Richard O; Feldmann, Joerg; Meharg, Andrew A; Haris, Parvez I

2011-02-01

Rice is elevated in arsenic (As) compared to other staple grains. The Bangladeshi community living in the United Kingdom (UK) has a ca. 30-fold higher consumption of rice than white Caucasians. In order to assess the impact of this difference in rice consumption, urinary arsenicals of 49 volunteers in the UK (Bangladeshi n = 37; white Caucasians n = 12) were monitored along with dietary habits. Total urinary arsenic (As(t)) and speciation analysis for dimethylarsinic acid (DMA), monomethylarsonic acid (MA) and inorganic arsenic (iAs) was conducted. Although no significant difference was found for As(t) (median: Bangladeshis 28.4 µg L(-1)) and white Caucasians (20.6 µg L(-1)), the sum of medians of DMA, MA and iAs for the Bangladeshi group was found to be over 3-fold higher (17.9 µg L(-1)) than for the Caucasians (3.50 µg L(-1)). Urinary DMA was significantly higher (p < 0.001) in the UK Bangladeshis (median: 16.9 µg DMA L(-1)) than in the white Caucasians (3.16 µg DMA L(-1)) as well as iAs (p < 0.001) with a median of 0.630 µg iAs L(-1) for Bangladeshi and 0.250 µg iAs L(-1) for Caucasians. Cationic compounds were significantly lower in the Bangladeshis (2.93 µg L(-1)) than in Caucasians (14.9 µg L(-1)). The higher DMA and iAs levels in the Bangladeshis are mainly the result of higher rice consumption: arsenic is speciated in rice as both iAs and DMA, and iAs can be metabolized, through MA, to DMA by humans. This study shows that a higher dietary intake of DMA alters the DMA/MA ratio in urine. Consequently, DMA/MA ratio as an indication of methylation capacity in populations consuming large quantities of rice should be applied with caution since variation in the quantity and type of rice eaten may alter this ratio.

Arsenic methylation capability and hypertension risk in subjects living in arseniasis-hyperendemic areas in southwestern Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Y.-K.; Tseng, C.-H.; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Background: Cumulative arsenic exposure (CAE) from drinking water has been shown to be associated with hypertension in a dose-response pattern. This study further explored the association between arsenic methylation capability and hypertension risk among residents of arseniasis-hyperendemic areas in Taiwan considering the effect of CAE and other potential confounders. Method: There were 871 subjects (488 women and 383 men) and among them 372 were diagnosed as having hypertension based on a positive history or measured systolic blood pressure {>=} 140 mm Hg and/or diastolic blood pressure {>=} 90 mm Hg. Urinary arsenic species were determined by high-performance liquid chromatography-hydride generatormore » and atomic absorption spectrometry. Primary arsenic methylation index [PMI, defined as monomethylarsonic acid (MMA{sup V}) divided by (As{sup III} + As{sup V})] and secondary arsenic methylation index (SMI, defined as dimethylarsinic acid divided by MMA{sup V}) were used as indicators for arsenic methylation capability. Results: The level of urinary arsenic was still significantly correlated with cumulative arsenic exposure (CAE) calculated from a questionnaire interview (p = 0.02) even after the residents stopped drinking the artesian well water for 2-3 decades. Hypertensive subjects had higher percentages of MMA{sup V} and lower SMI than subjects without hypertension. However, subjects having CAE > 0 mg/L-year had higher hypertension risk than those who had CAE = 0 mg/L-year disregard a high or low methylation index. Conclusion: Inefficient arsenic methylation ability may be related with hypertension risk.« less

A biological indicator of inorganic arsenic exposure using the sum of urinary inorganic arsenic and monomethylarsonic acid concentrations

PubMed Central

Hata, Akihisa; Kurosawa, Hidetoshi; Endo, Yoko; Yamanaka, Kenzo; Fujitani, Noboru; Endo, Ginji

2016-01-01

Objectives: The sum of urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) concentrations is used for the biological monitoring of occupational iAs exposure. Although DMA is a major metabolite of iAs, it is an inadequate index because high DMA levels are present in urine after seafood consumption. We estimated the urinary iAs+MMA concentration corresponding to iAs exposure. Methods: We used data from two arsenic speciation analyses of urine samples from 330 Bangladeshi with oral iAs exposure and 172 Japanese workers without occupational iAs exposure using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Results: iAs, MMA, and DMA, but not arsenobetaine (AsBe), were detected in the urine of the Bangladeshi subjects. The correlation between iAs+MMA+DMA and iAs+MMA was obtained as log (iAs+MMA) = 1.038 log (iAs+MMA+DMA) -0.658. Using the regression formula, the iAs+MMA value was calculated as 2.15 and 7.5 μg As/l, corresponding to 3 and 10 μg As/m3 of exposures, respectively. In the urine of the Japanese workers, arsenic was mostly excreted as AsBe. We used the 95th percentile of iAs+MMA (12.6 μg As/l) as the background value. The sum of the calculated and background values can be used as a biological indicator of iAs exposure. Conclusion: We propose 14.8 and 20.1 μg As/l of urinary iAs+MMA as the biological indicators of 3 and 10 μg As/m3 iAs exposure, respectively. PMID:27010090

Multimedia Exposures to Arsenic and Lead for Children Near an Inactive Mine Tailings and Smelter Site

PubMed Central

Loh, Miranda M.; Sugeng, Anastasia; Lothrop, Nathan; Klimecki, Walter; Cox, Melissa; Wilkinson, Sarah T.; Lu, Zhenqiang; Beamer, Paloma I.

2016-01-01

Children living near contaminated mining waste areas may have high exposures to metals from the environment. This study investigates whether exposure to arsenic and lead is higher in children in a community near a legacy mine and smelter site in Arizona compared to children in other parts of the United States and the relationship of that exposure to the site. Arsenic and lead were measured in residential soil, house dust, tap water, urine, and toenail samples from 70 children in 34 households up to 7 miles from the site. Soil and house dust were sieved, digested, and analyzed via ICP-MS. Tap water and urine were analyzed without digestion, while toenails were washed, digested and analyzed. Blood lead was analyzed by an independent, certified laboratory. Spearman correlation coefficients were calculated between each environmental media and urine and toenails for arsenic and lead. Geometric mean arsenic (standard deviation) concentrations for each matrix were: 22.1 (2.59) ppm and 12.4 (2.27) ppm for soil and house dust (<63 μm), 5.71 (6.55) ppb for tap water, 14.0 (2.01) μg/L for specific gravity-corrected total urinary arsenic, 0.543 (3.22) ppm for toenails. Soil and vacuumed dust lead concentrations were 16.9 (2.03) ppm and 21.6 (1.90) ppm. The majority of blood lead levels were below the limit of quantification. Arsenic and lead concentrations in soil and house dust decreased with distance from the site. Concentrations in soil, house dust, tap water, along with floor dust loading were significantly associated with toenail and urinary arsenic but not lead. Mixed models showed that soil and tap water best predicted urinary arsenic. In our study, despite being present in mine tailings at similar levels, internal lead exposure was not high, but arsenic exposure was of concern, particularly from soil and tap water. Naturally occurring sources may be an additional important contributor to exposures in certain legacy mining areas. PMID:26803211

Creatinine, diet, micronutrients, and arsenic methylation in West Bengal, India.

PubMed

Basu, Arin; Mitra, Soma; Chung, Joyce; Guha Mazumder, D N; Ghosh, Nilima; Kalman, David; von Ehrenstein, Ondine S; Steinmaus, Craig; Liaw, Jane; Smith, Allan H

2011-09-01

Ingested inorganic arsenic (InAs) is methylated to monomethylated (MMA) and dimethylated metabolites (DMA). Methylation may have an important role in arsenic toxicity, because the monomethylated trivalent metabolite [MMA(III)] is highly toxic. We assessed the relationship of creatinine and nutrition--using dietary intake and blood concentrations of micronutrients--with arsenic metabolism, as reflected in the proportions of InAS, MMA, and DMA in urine, in the first study that incorporated both dietary and micronutrient data. We studied methylation patterns and nutritional factors in 405 persons who were selected from a cross-sectional survey of 7,638 people in an arsenic-exposed population in West Bengal, India. We assessed associations of urine creatinine and nutritional factors (19 dietary intake variables and 16 blood micronutrients) with arsenic metabolites in urine. Urinary creatinine had the strongest relationship with overall arsenic methylation to DMA. Those with the highest urinary creatinine concentrations had 7.2% more arsenic as DMA compared with those with low creatinine (p < 0.001). Animal fat intake had the strongest relationship with MMA% (highest tertile animal fat intake had 2.3% more arsenic as MMA, p < 0.001). Low serum selenium and low folate were also associated with increased MMA%. Urine creatinine concentration was the strongest biological marker of arsenic methylation efficiency, and therefore should not be used to adjust for urine concentration in arsenic studies. The new finding that animal fat intake has a positive relationship with MMA% warrants further assessment in other studies. Increased MMA% was also associated, to a lesser extent, with low serum selenium and folate.

Individual differences in arsenic metabolism and lung cancer in a case-control study in Cordoba, Argentina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinmaus, Craig, E-mail: craigs@berkeley.ed; School of Public Health, University of California, Berkeley, CA; Yuan Yan

2010-09-01

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although in most people this process is not complete. Previous studies have identified associations between the proportion of urinary MMA (%MMA) and increased risks of several arsenic-related diseases, although none of these reported on lung cancer. In this study, urinary arsenic metabolites were assessed in 45 lung cancer cases and 75 controls from arsenic-exposed areas in Cordoba, Argentina. Folate has also been linked to arsenic-disease susceptibility, thus an exploratory assessment of associations between single nucleotide polymorphisms in folate metabolizing genes, arsenic methylation, and lung cancer wasmore » also conducted. In analyses limited to subjects with metabolite concentrations above detection limits, the mean %MMA was higher in cases than in controls (17.5% versus 14.3%, p = 0.01). The lung cancer odds ratio for subjects with %MMA in the upper tertile compared to those in the lowest tertile was 3.09 (95% CI, 1.08-8.81). Although the study size was too small for a definitive conclusion, there was an indication that lung cancer risks might be highest in those with a high %MMA who also carried cystathionine {beta}-synthase (CBS) rs234709 and rs4920037 variant alleles. This study is the first to report an association between individual differences in arsenic metabolism and lung cancer, a leading cause of arsenic-related mortality. These results add to the increasing body of evidence that variation in arsenic metabolism plays an important role in arsenic-disease susceptibility.« less

The effect of the Environmental Protection Agency maximum contaminant level on arsenic exposure in the USA from 2003 to 2014: an analysis of the National Health and Nutrition Examination Survey (NHANES).

PubMed

Nigra, Anne E; Sanchez, Tiffany R; Nachman, Keeve E; Harvey, David; Chillrud, Steven N; Graziano, Joseph H; Navas-Acien, Ana

2017-11-01

The current US Environmental Protection Agency (EPA) maximum contaminant level (MCL) for arsenic in public water systems (10 µg/L) took effect in 2006. Arsenic is not federally regulated in private wells. The impact of the 2006 MCL on arsenic exposure in the US, as confirmed through biomarkers, is presently unknown. We evaluated national trends in water arsenic exposure in the US, hypothesizing that urinary arsenic levels would decrease over time among participants using public water systems but not among those using well water. We further estimated the expected number of avoided lung, bladder, and skin cancer cases. We evaluated 14,127 participants in the National Health and Nutrition Examination Survey (NHANES) 2003-2014 with urinary dimethylarsinate (DMA) and total arsenic available. To isolate water exposure, we expanded a residual-based method to remove tobacco and dietary contributions of arsenic. We applied EPA risk assessment approaches to estimate the expected annual number of avoided cancer cases comparing arsenic exposure in 2013-2014 vs. 2003-2004. Among public water users, fully adjusted geometric means (GMs) of DMA decreased from 3.01 µg/L in 2003-2004 to 2.49 µg/L in 2013-2014 (17% reduction; 95% confidence interval 10%, 24%; p-trend<0.01); no change was observed among well water users (p-trend= 0.35). Assuming these estimated exposure reductions will remain similar across a lifetime, we estimate a reduction of 200 to 900 lung and bladder cancer cases per year depending on the approach used. The decline in urinary arsenic among public water but not private well users in NHANES 2003-2014 indicates that the implementation of the current MCL has reduced arsenic exposure in the US population. Our study supports prior work showing that well water users are inadequately protected against drinking water arsenic, and confirms the critical role of federal drinking water regulations in reducing toxic exposures and protecting human health. This work was supported by the National Institute of Environmental Health Sciences (1R01ES025216, R01ES021367, 5P30ES009089 and P42ES010349). A. E. Nigra was supported by 5T32ES007322.

GENE EXPRESSION CAN DIFFERENTIATE CARCINOGENIC FROM NON-CARCINOGENIC DOSES OF DIMETHYLARSINIC ACID (DMAv) IN THE TRANSITIONAL EPITHELIUM OF THE URINARY BLADDER FROM FEMALE F344 RATS

EPA Science Inventory

Arsenic is an environmental concern worldwide, and drinking arsenic contaminated water has been associated with increased incidences of skin, lung and bladder cancer. Dimethylarsinic acid (DMAv) is a major metabolite of inorganic arsenic in rodents and humans and is the predomina...

Arsenic Methylation and Lung and Bladder Cancer in a Case-control Study in Northern Chile

PubMed Central

Melak, Dawit; Ferreccio, Catterina; Kalman, David; Parra, Roxana; Acevedo, Johanna; Pérez, Liliana; Cortés, Sandra; Smith, Allan H; Yuan, Yan; Liaw, Jane; Steinmaus, Craig

2014-01-01

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., <200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend <0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend <0.001). In analyses confined to subjects only with arsenic water concentrations <200 μg/L (median=60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. PMID:24296302

DIETARY ARSENIC EXPOSURE ASSESSMENT USING ENZYMATIC BASED EXTRACTION CONDITIONS AND DETECTION OF URINARY THIO-ARSENICALS AS METABOLITES OF EXPOSURE - MCEARD2

EPA Science Inventory

Inorganic arsenic is classified as a carcinogen and has been linked to lung and bladder cancer as well as other non-cancerous health effects. Because of these health effects the U.S. EPA has set a Maximum Contaminant Level (MCL) at 10ppb based on a linear extrapolation of risk an...

The relationships between arsenic methylation and both skin lesions and hypertension caused by chronic exposure to arsenic in drinking water.

PubMed

Wei, Binggan; Yu, Jiangping; Wang, Jing; Yang, Linsheng; Li, Hairong; Kong, Chang; Xia, Yajuan; Wu, Kegong

2017-07-01

The associations between arsenic exposure, arsenic methylation, and the prevalence of skin lesions and hypertension are investigated. The results indicate that the HS (hypertension and skin lesions) group and the S (skin lesions) group have higher urinary concentrations of iAs (inorganic arsenic), MMA (monomethylarsonic acid), DMA (dimethylarsinous acid) and%MMA, and lower SMI (secondary arsenic methylation index) compared to the H (hypertension) and N (without both hypertension and skin lesions) groups. The arsenic content in water which caused H may be lower than that which caused HS and S. In addition, the odds ratios suggest that higher urinary concentrations of iAs and MMA, %iAs, %MMA and PMI elevate the prevalence of only hypertension and skin lesions, and both hypertension and skin lesions. However, higher%DMA and SMI, and lower%MMA increase the prevalence of both hypertension and skin lesions compared to that of only skin lesions. It can be concluded that skin lesions subjects have higher prevalence of hypertension. Hypertension subjects may have higher prevalence of skin lesions. Lower%DMA and SMI, higher%iAs, %MMA and PMI enhance the prevalence of only hypertension and skin lesions, and both hypertension and skin lesions. Moreover, iAs and MMA may have higher toxicity and lead to both hypertension and skin lesions than to only hypertension. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, M.-M.; Graduate Institute of Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan; Chiou, H.-Y.

2006-10-01

Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA{sup V}) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA{sup V} (MMA%) was calculated bymore » dividing with total arsenic species in urine, including arsenite, arsenate, MMA{sup V}, and dimethylarsinic acid (DMA{sup V}). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% ({>=}16.5%) and high homocysteine levels ({>=}12.7 {mu}mol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 {mu}mol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine.« less

Analysis of maternal polymorphisms in arsenic (+3 oxidation state)-methyltransferase AS3MT and fetal sex in relation to arsenic metabolism and infant birth outcomes: Implications for risk analysis.

PubMed

Drobná, Zuzana; Martin, Elizabeth; Kim, Kyung Su; Smeester, Lisa; Bommarito, Paige; Rubio-Andrade, Marisela; García-Vargas, Gonzalo G; Stýblo, Miroslav; Zou, Fei; Fry, Rebecca C

2016-06-01

Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the metabolism of inorganic arsenic (iAs). Polymorphisms of AS3MT influence adverse health effects in adults, but little is known about their role in iAs metabolism in pregnant women and infants. The relationships between seven single nucleotide polymorphisms (SNPs) in AS3MT and urinary concentrations of iAs and its methylated metabolites were assessed in mother-infant pairs of the Biomarkers of Exposure to ARsenic (BEAR) cohort. Maternal alleles for five of the seven SNPs (rs7085104, rs3740400, rs3740393, rs3740390, and rs1046778) were associated with urinary concentrations of iAs metabolites, and alleles for one SNP (rs3740393) were associated with birth outcomes/measures. These associations were strongly dependent upon the male sex of the fetus but independent of fetal genotype for AS3MT. These data highlight a potential sex-dependence of the relationships among maternal genotype, iAs metabolism and infant health outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women.

PubMed

Pineda-Belmontes, Cristina P; Hernández-Ramírez, Raúl U; Hernández-Alcaraz, César; Cebrián, Mariano E; López-Carrillo, Lizbeth

2016-04-01

To evaluate whether the presence of polymorphisms of peroxisome proliferator-activated receptor gamma PPARγ (Pro 1 2Ala) and PPARGC1B (Ala203Pro) modifies the association between the inorganic arsenic (iAs) methylation capacity and breast cancer (BC). Mexican women were interviewed, and blood and urine samples were collected from them (cases/controls= 197/220). The concentration of urinary arsenic species and the polymorphisms of interest were determined by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and polymerase chain reaction (PCR), respectively. In women with a high %MMA (urinary monomethyl arsenic) and high primary methylation ratio (PM = MMA/iAs), the risk of BC was increased (odds ratio [OR]%MMA T3 vs.T1= 3.60: 95% confidence interval [CI] 2.02-6.41, ORPMI T3 vs.T1= 3.47: 95%CI 1.95-6.17), which was maintained after adjusting for polymorphisms. No significant interactions were observed between the polymorphisms and the arsenic variables on the risk of BC. Pro 12Ala and Ala203Pro polymorphisms did not modify the association between the iAs methylation capacity and BC.

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com; School of Medicine, University Juarez of Durango, Gomez Palacio, Durango; Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatorymore » biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels • In 275 children chronically exposed to As, 3 biomarkers were measured. • Negative associations were found between DMA, %MMA and %DMA with sRAGE. • Positive associations were found between %DMA with MMP-9 and with the MMP-9/TIMP-1 ratio. • Chronic arsenic exposure-induced alterations in lung inflammatory biomarkers in children.« less

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cárdenas-González, M.

Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5–12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples hadmore » levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6 ppb) and chromium (61.7 ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467 pg/mL; T3: 615 pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372 pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. - Highlights: • Children living in Mexico had exceedingly high arsenic and chromium exposure. • Arsenic and chromium exposure was significantly associated with urinary KIM-1. • KIM-1 might serve as a sensitive biomarker to evaluate kidney injury in children.« less

METABOLSM OF PENTAVALENT AND TRIVALENT DIMETHYLARSENIC ARSENIC IN THE MOUSE

EPA Science Inventory

Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen after chronic exposure in either drinking water or the diet. DMA(V) is also a major urinary metabolite of mammals exposed to inorganic arsenic. In mice, iv and po administration of [¹⁴C]-DMA(V) results in rapi...

Association between arsenic exposure from drinking water and hematuria: results from the Health Effects of Arsenic Longitudinal Study.

PubMed

McClintock, Tyler R; Chen, Yu; Parvez, Faruque; Makarov, Danil V; Ge, Wenzhen; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Slavkovich, Vesna; Bjurlin, Marc A; Graziano, Joseph H; Ahsan, Habibul

2014-04-01

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend<0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04-1.59), 1.41 (95% CI: 1.15-1.74), 1.46 (95% CI: 1.19-1.79), and 1.56 (95% CI: 1.27-1.91). Compared to those with relatively little absolute urinary As change during follow-up (-10.40 to 41.17 μg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80-1.22) and 0.80 (95% CI: 0.65-0.99) for those whose urinary As decreased by >47.49 μg/l and 10.87 to 47.49 μg/l since last visit, respectively, and 1.17 (95% CI: 0.94-1.45) and 1.36 (95% CI: 1.10-1.66) for those with between-visit increases of 10.40 to 41.17 μg/l and >41.17 μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As. Copyright © 2014 Elsevier Inc. All rights reserved.

Association between arsenic exposure from drinking water and hematuria: results from the Health Effects of Arsenic Longitudinal Study

PubMed Central

McClintock, Tyler R.; Chen, Yu; Parvez, Faruque; Makarov, Danil V.; Ge, Wenzhen; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Slavkovich, Vesna; Bjurlin, Marc A.; Graziano, Joseph H.; Ahsan, Habibul

2014-01-01

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7,843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend < 0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04–1.59), 1.41 (95% CI: 1.15–1.74), 1.46 (95% CI: 1.19–1.79), and 1.56 (95% CI: 1.27–1.91). Compared to those with relatively little absolute urinary As change during follow-up (−10.40 to 41.17 μg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80–1.22) and 0.80 (95% CI: 0.65–0.99) for those whose urinary As decreased by >47.49 μg/l and 10.87 to 47.49 μg/l since last visit, respectively, and 1.17 (95% CI: 0.94–1.45) and 1.36 (95% CI: 1.10–1.66) for those with between-visit increases of 10.40 to 41.17 μg/l and >41.17 μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by short-term changes in drinking water As. PMID:24486435

Association between arsenic exposure from drinking water and proteinuria: results from the Health Effects of Arsenic Longitudinal Study

PubMed Central

Chen, Yu; Parvez, Faruque; Liu, Mengling; Pesola, Gene R; Gamble, Mary V; Slavkovich, Vesna; Islam, Tariqul; Ahmed, Alauddin; Hasan, Rabiul; Graziano, Joseph H; Ahsan, Habibul

2011-01-01

Background Proteinuria has been recognized as a marker for an increased risk of chronic renal disease. It is unclear whether arsenic (As) exposure from drinking water is associated with proteinuria. Methods We evaluated the association between As exposure from drinking water and proteinuria in 11 122 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Proteinuria was detected by urinary dipstick tests at baseline and at 2-year intervals. As exposure variables included baseline well As and changes in urinary As during follow-up modelled as time-dependent variables in the analyses. Results At baseline, well As was positively related to prevalence of proteinuria; prevalence odds ratios (PORs) for proteinuria in increasing quintiles of well As (≤7, 8–39, 40–91, 92–179 and 180–864 µg/l) were 1.00 (ref), POR 0.99 [95% confidence interval (CI) 0.77–1.27], POR 1.23 (95% CI 0.97–1.57), POR 1.50 (95% CI 1.18–1.89) and POR 1.59 (95% CI 1.26–2.00) (P for trend <0.01). Hazard ratios for incidence of proteinuria were POR 0.83 (95% CI 0.67–1.03) and POR 0.91 (95% CI 0.74–1.12) for participants with a decreasing level of >70 and 17–70 µg/l in urinary As over time, respectively, and were POR 1.17 (95% CI 0.97–1.42) and POR 1.42 (95% CI 1.16–1.73) for participants with an increasing level of 16–68 and >68 µg/l in urinary As over time, respectively, compared with the group with relatively little changes in urinary As as the reference group (urinary As −16 to 15 µg/l). Conclusion The findings suggest that there are adverse effects of As exposure on the risk of proteinuria and the effects are modifiable by recent changes in As exposure. PMID:21343184

Randomized placebo-controlled trial of 2,3-dimercapto-1-propanesulfonate (DMPS) in therapy of chronic arsenicosis due to drinking arsenic-contaminated water.

PubMed

Guha Mazumder, D N; De, B K; Santra, A; Ghosh, N; Das, S; Lahiri, S; Das, T

2001-01-01

Chronic arsenic toxicity, producing various clinical manifestations, is currently epidemic in West Bengal, India, Bangladesh, and other regions of the world. 2,3-Dimercapto-1-propanesulfonate, a chelating agent, increases excretion of arsenic in urine to several times the prechelation concentration but the therapeutic efficacy of 2,3-dimercapto-1-propanesulfonate in the management of chronic arsenic toxicity has been incompletely evaluated. We investigated the clinical use of 2,3-dmercapto-1-propanesulfonate in such patients. Twenty-one consecutive patients with chronic arsenicosis were individually randomized into 2 groups: 11 patients (9 males and 2 females, age 30.63+/-11.4 years) received 2,3-dimercapto-1-propanesulfonate 100-mg capsules 4 times a day for 1 week and repeated in the 3rd, 5th, and 7th week with no drug during the intervening period. The other 10 patients (5 males and 5 females, age 34.4+/-14.41 years) were given placebo capsules (resembling 2,3-dimercapto-1-propanesulfonate) in the same schedule. The consumption of arsenic-contaminated water was terminated by all 21 subjects. Initial and posttreatment urinary arsenic excretion was determined in all cases. Sequential excretion of urinary arsenic was determined during the treatment of 2 drug- and 1 placebo-treated cases. The clinical features were evaluated by an objective scoring system before and after treatment. Routine investigation including liver function test and skin biopsy were also done before and after the treatment. Drug-associated toxicity was tabulated. Therapy with 2,3-dimercapto-1-propanesulfonate caused significant improvement in the clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90+/-2.84 to 3.27+/-1.73; p < 0.0001. Exposure cessation alone with placebo treatment also reduced clinical scores (8.50+/-1.96 to 5.40+/-2.12; p < 0.003), but the posttreatment total clinical score of 2,3-dimercapto-1-propanesulfonate-treated patients (3.27+/-1.73) was significantly lower than that of placebo-treated patients (5.40+/-2.12; p < 0.01). The most significant improvement was noted in regard to the clinical scores of weakness, pigmentation, and lung disease. No difference was noted between groups in the hematological and biochemical parameters (which were normal) and skin histology before and after treatment. No 2,3-dimercapto-1-propanesulfonate-related adverse effects were noted. Total urinary excretion of arsenic in 2,3-dimercapto-1-propanesulfonate-treated cases increased significantly following drug therapy, with no increase in placebo-treated cases. 2,3-Dimercapto-1-propanesulfonate treatment caused significant improvement in the clinical score of patients suffering from chronic arsenic toxicity. Increased urinary excretion of arsenic during the period of therapy is the possible cause of this improvement.

Low-level inorganic arsenic exposure and neuropsychological functioning in American Indian elders.

PubMed

Carroll, Clint R; Noonan, Carolyn; Garroutte, Eva M; Navas-Acien, Ana; Verney, Steven P; Buchwald, Dedra

2017-07-01

Inorganic arsenic at high and prolonged doses is highly neurotoxic. Few studies have evaluated whether long-term, low-level arsenic exposure is associated with neuropsychological functioning in adults. To investigate the association between long-term, low-level inorganic arsenic exposure and neuropsychological functioning among American Indians aged 64-95. We assessed 928 participants in the Strong Heart Study by using data on arsenic species in urine samples collected at baseline (1989-1991) and results of standardized tests of global cognition, executive functioning, verbal learning and memory, fine motor functioning, and speed of mental processing administered during comprehensive follow-up evaluations in 2009-2013. We calculated the difference in neuropsychological functioning for a 10% increase in urinary arsenic with adjustment for sex, age, education, and study site. The sum of inorganic and methylated arsenic species (∑As) in urine was associated with limited fine motor functioning and processing speed. A 10% increase in ∑As was associated with a .10 (95% CI -.20, -.01) decrease on the Finger Tapping Test for the dominant hand and a .13 decrease (95% CI -.21, -.04) for the non-dominant hand. Similarly, a 10% increase in ∑As was associated with a .15 (95% CI -.29, .00) decrease on the Wechsler Adult Intelligence Scale-Fourth Edition Coding Subtest. ∑As was not associated with other neuropsychological functions. Findings indicate an adverse association between increased urinary arsenic fine motor functioning and processing speed, but not with other neuropsychological functioning, among elderly American Indians. Copyright © 2017 Elsevier Inc. All rights reserved.

Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level

PubMed Central

Xu, Xiaofan; Drobná, Zuzana; Voruganti, V. Saroja; Barron, Keri; González-Horta, Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Cerón, Roberto Hernández; Morales, Damián Viniegra; Terrazas, Francisco A. Baeza; Ishida, María C.; Gutiérrez-Torres, Daniela S.; Saunders, R. Jesse; Crandell, Jamie; Fry, Rebecca C.; Loomis, Dana; García-Vargas, Gonzalo G.; Del Razo, Luz M.; Stýblo, Miroslav; Mendez, Michelle A.

2016-01-01

Abstract Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P < .05). In contrast, for 1 variant (rs17881215), associations were significantly stronger at exposures ≤50 ppb. Results suggest that iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism—and perhaps with susceptibility to iAs-associated disease—may vary in settings with exposure level. PMID:27370415

Health Risk Assessment and Urinary Excretion of Children Exposed to Arsenic through Drinking Water and Soils in Sonora, Mexico.

PubMed

García-Rico, Leticia; Meza-Figueroa, Diana; Jay Gandolfi, A; Del Rivero, Carlos Ibañez; Martínez-Cinco, Marco A; Meza-Montenegro, Maria M

2018-05-02

Environmental arsenic exposure is associated with increased risk of non-cancerous chronic diseases and a variety of cancers in humans. The aims of this study were to carry out for the first time a health risk assessment for two common arsenic exposure routes (drinking water and soil ingestion) in children living in the most important agricultural areas in the Yaqui and Mayo valleys in Sonora, Mexico. Drinking water sampling was conducted in the wells of 57 towns. A cross-sectional study was done in 306 children from 13 villages in the valleys. First morning void urine samples were analyzed for inorganic arsenic (InAs) and monomethyl and dimethyl arsenic (MMA and DMA) by HPLC/ICP-MS. The results showed a wide range of arsenic levels in drinking water between 2.7 and 98.7 μg As/L. Arsenic levels in agricultural and backyard soils were in the range of < 10-27 mg As/kg. The hazard index (HI) = ∑hazard quotient (HQ) for drinking water, agricultural soil, and backyard soil showed values > 1 in 100% of the study towns, and the carcinogenic risk (CR) was greater than 1E-04 in 85%. The average of arsenic excreted in urine was 31.7 μg As/L, and DMA had the highest proportion in urine, with averages of 77.8%, followed by InAs and MMA with 11.4 and 10.9%, respectively, percentages similar to those reported in the literature. Additionally, positive correlations between urinary arsenic levels and HI values were found (r = 0.59, P = 0.000). These results indicated that this population is at high risk of developing chronic diseases including cancer.

Dietary B Vitamin Intake Is Associated with Lower Urinary Monomethyl Arsenic and Oxidative Stress Marker 15-F2t-Isoprostane among New Hampshire Adults.

PubMed

Howe, Caitlin G; Li, Zhigang; Zens, Michael S; Palys, Thomas; Chen, Yu; Channon, Jacqueline Y; Karagas, Margaret R; Farzan, Shohreh F

2017-12-01

Background: Arsenic exposure has been associated with an increased risk of cardiovascular disease (CVD). Growing evidence suggests that B vitamins facilitate arsenic metabolism and may protect against arsenic toxicity. However, to our knowledge, few studies have evaluated this in US populations. Objective: Our objective was to examine whether higher B vitamin intake is associated with enhanced arsenic metabolism and lower concentrations of preclinical markers of CVD among New Hampshire adults. Methods: We used weighted quantile sum (WQS) regression to evaluate the collective impact of 6 dietary B vitamins (thiamin, riboflavin, folate, niacin, and vitamins B-6 and B-12) on 1 ) the proportion of arsenic metabolites in urine and 2 ) 6 CVD-related markers [including urinary 15-F 2t -isoprostane (15-F 2t -IsoP)] among 418 participants (26-75 y of age) from the New Hampshire Health Study. Contributions of arsenic metabolites to B vitamin-CVD marker associations were also explored in structural equation models. Results: In WQS models, the weighted sum of B vitamin intakes from food sources was inversely associated with the proportion of monomethyl arsenic species in urine (uMMA) (β: -1.03; 95% CI: -1.91, -0.15; P = 0.02). Thiamin and vitamins B-6 and B-12 contributed the most to this association, whereas riboflavin had a negligible effect. Higher overall B vitamin intake was also inversely associated with 15-F 2t -IsoP (β: -0.21; 95% CI: -0.32, -0.11; P < 0.01), with equal contributions from the 6 B vitamins, which was partially explained by differences in the proportion of uMMA (indirect effect β: -0.01; 95% CI: -0.04, -0.00). Conclusions: Among New Hampshire adults, higher intakes of certain B vitamins (particularly thiamin and vitamins B-6 and B-12 from food sources) may reduce the proportion of uMMA, an intermediate of arsenic metabolism that has been associated with an increased risk of CVD. Higher overall B vitamin intake may also reduce urinary 15-F 2t -IsoP, a marker of oxidative stress and potential risk factor for CVD, in part by reducing the proportion of uMMA. © 2017 American Society for Nutrition.

SNPs of GSTM1, T1, P1, epoxide hydrolase and DNA repair enzyme XRCC1 and risk of urinary transitional cell carcinoma in southwestern Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, L.-I; Chiu, Allen W.; Huan, Steven K.

A hospital-based case-control study was conducted near a former black-foot disease (BFD)-endemic area in southwestern Taiwan to examine the possible risk factors and genetic susceptibility for urinary transitional cell carcinoma (TCC). A total of 221 patients with pathologically confirmed TCC and 223 age-sex-matched control subjects from urology outpatient clinics were recruited between 1998 and 2002. The results showed that residency in the BFD area and consumption of well water for more than 10 years was a strong factor on urinary cancer risk (odds ratio [OR],8.16, 95% confidence interval [CI],3.34-19.90, p < 0.0001). Dose response relationship between average arsenic concentration inmore » well water and TCC risk was also observed. Cigarette smoking played a relatively minor role in urinary carcinogenesis in this study. The GSTP1 Ile105Val A {yields} G polymorphism was significantly associated with cancer risk (A/G + G/G: OR = 0.60, 95%CI = 0.39-0.94, p = 0.02), and the effect of Val105 allele was largely confined to the subjects diagnosed earlier than 55 years old (A/G + G/G: OR,0.29; 95% CI, 0.09-0.87, p = 0.03). The results suggest that GSTP1 is a candidate for susceptibility locus and Ile105 allele may predispose individuals to early-onset urinary TCC. The GSTM1 null genotype was associated with tumors of high-invasiveness (OR,2.21; 95% CI, 1.34-4.73) as well as with early-onset TCC risk (OR,2.53; 95% CI, 0.97-6.59). Our preliminary results showed the XRCC1 Arg194Trp were associated with arsenic-related urinary TCC and the interaction between the genotype and the exposure was statistically significant. The modulating effect of the GSTM1, GSTT1, GSTP1 Ile105Val, EPHX Tyr113His and XRCC1 Arg280His on arsenic-related TCC risk was also suggestive. These observations implied that impaired metabolism of carcinogenic exposure as well as impaired DNA repair function play an important role in arsenic-related urinary transitional cell carcinogenesis.« less

Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melak, Dawit; Ferreccio, Catterina; Kalman, David

2014-01-15

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., < 200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung andmore » 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend < 0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend < 0.001). In analyses confined to subjects only with arsenic water concentrations < 200 μg/L (median = 60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. - Highlights: • Urine arsenic metabolites were measured in cancer cases and controls from Chile. • Higher urine %MMA values were associated with increased lung and bladder cancer. • %MMA-cancer associations were seen at drinking water arsenic levels < 200 μg/L.« less

Estimated Exposure to Arsenic in Breastfed and Formula-Fed Infants in a United States Cohort

PubMed Central

Carignan, Courtney C.; Jackson, Brian P.; Farzan, Shohreh F.; Gandolfi, A. Jay; Punshon, Tracy; Folt, Carol L.; Karagas, Margaret R.

2015-01-01

Background: Previous studies indicate that concentrations of arsenic in breast milk are relatively low even in areas with high drinking-water arsenic. However, it is uncertain whether breastfeeding leads to reduced infant exposure to arsenic in regions with lower arsenic concentrations. Objective: We estimated the relative contributions of breast milk and formula to arsenic exposure during early infancy in a U.S. population. Methods: We measured arsenic in home tap water (n = 874), urine from 6-week-old infants (n = 72), and breast milk from mothers (n = 9) enrolled in the New Hampshire Birth Cohort Study (NHBCS) using inductively coupled plasma mass spectrometry. Using data from a 3-day food diary, we compared urinary arsenic across infant feeding types and developed predictive exposure models to estimate daily arsenic intake from breast milk and formula. Results: Urinary arsenic concentrations were generally low (median, 0.17 μg/L; maximum, 2.9 μg/L) but 7.5 times higher for infants fed exclusively with formula than for infants fed exclusively with breast milk (β = 2.02; 95% CI: 1.21, 2.83; p < 0.0001, adjusted for specific gravity). Similarly, the median estimated daily arsenic intake by NHBCS infants was 5.5 times higher for formula-fed infants (0.22 μg/kg/day) than for breastfed infants (0.04 μg/kg/day). Given median arsenic concentrations measured in NHBCS tap water and previously published for formula powder, formula powder was estimated to account for ~ 70% of median exposure among formula-fed NHBCS infants. Conclusions: Our findings suggest that breastfed infants have lower arsenic exposure than formula-fed infants, and that both formula powder and drinking water can be sources of exposure for U.S. infants. Citation: Carignan CC, Cottingham KL, Jackson BP, Farzan SF, Gandolfi AJ, Punshon T, Folt CL, Karagas MR. 2015. Estimated exposure to arsenic in breastfed and formula-fed infants in a United States cohort. Environ Health Perspect 123:500–506; http://dx.doi.org/10.1289/ehp.1408789 PMID:25707031

Impact of lifestage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice.

EPA Science Inventory

Epidemiological studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Previous experimental studies have demonstrated increased incidence of liver, lung, ovary, and uterine tumo...

CHARACTERIZATION OF HUMAN URINARY BLADDER CELL LINE UROTSA TRANSDUCED WITH RAT ASLLL-METHYLTRANSFERASE

EPA Science Inventory

In humans, the biomethylation of arsenic (As) is catalyzed by an As(III)-methyltransferase (Cyt19) and yields pentavalent and trivalent methylated arsenicals. Cyt19 activity and expression levels vary among tissues. For example, Cyt19 mRNA is not detected in UROtsa cells, a h...

Unusual arsenic metabolism in Giant Pandas.

PubMed

Braeuer, Simone; Dungl, Eveline; Hoffmann, Wiebke; Li, Desheng; Wang, Chengdong; Zhang, Hemin; Goessler, Walter

2017-12-01

The total arsenic concentration and the arsenic speciation in urine and feces samples of the two Giant Pandas living at Vienna zoo and of their feed, bamboo, were determined with ICPMS and HPLC-ICPMS. Urine was the main excretion route and accounted for around 90% of the ingested arsenic. The urinary arsenic concentrations were very high, namely up to 179 μg/L. Dimethylarsinic acid (DMA) was the dominating arsenic compound in the urine samples and ranged from 73 to 92% of the total arsenic, which is unusually high for a terrestrial mammal. The feces samples contained around 70% inorganic arsenic and 30% DMA. The arsenic concentrations in the bamboo samples were between 16 and 920 μg/kg dry mass. The main arsenic species in the bamboo extracts was inorganic arsenic. This indicates that the Giant Panda possesses a unique way of very efficiently methylating and excreting the provided inorganic arsenic. This could be essential for the survival of the animal in its natural habitat, because parts of this area are contaminated with arsenic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transplacental Arsenic Carcinogenesis in Mice

PubMed Central

Waalkes, Michael P.; Liu, Jie; Diwan, Bhalchandra A.

2007-01-01

Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from day 8 to 18 of gestation, and the offspring were observed for up to two years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans and investigating a potential transplacental component of the human carcinogenic response to arsenic should be a research priority. PMID:17306315

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yokohira, Masanao; Arnold, Lora L.; Pennington, Karen L.

Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes reactions which convert inorganic arsenic to methylated metabolites. This study determined whether the As3mt null genotype in the mouse modifies cytotoxic and proliferative effects seen in urinary bladders of wild type mice after exposure to inorganic arsenic. Female wild type C57BL/6 mice and As3mt KO mice were divided into 3 groups each (n = 8) with free access to a diet containing 0, 100 or 150 ppm of arsenic as arsenite (As{sup III}). During the first week of As{sup III} exposure, As3mt KO mice exhibited severe and lethal systemic toxicity. At termination,more » urinary bladders of both As3mt KO and wild type mice showed hyperplasia by light microscopy. As expected, arsenic-containing granules were found in the superficial urothelial layer of wild type mice. In As3mt KO mice these granules were present in all layers of the bladder epithelium and were more abundant and larger than in wild type mice. Scanning electron microscopy of the bladder urothelium of As3mt KO mice treated with 100 ppm As{sup III} showed extensive superficial necrosis and hyperplastic changes. In As3mt KO mice, livers showed severe acute inflammatory changes and spleen size and lymphoid areas were decreased compared with wild type mice. Thus, diminished arsenic methylation in As3mt KO mice exacerbates systemic toxicity and the effects of As{sup III} on the bladder epithelium, showing that altered kinetic and dynamic behavior of arsenic can affect its toxicity.« less

Spatial and Temporal Variations in Arsenic Exposure via Drinking-water in Northern Argentina

PubMed Central

Concha, Gabriela; Nermell, Barbro

2006-01-01

This study evaluated the spatial, temporal and inter-individual variations in exposure to arsenic via drinking-water in Northern Argentina, based on measurements of arsenic in water, urine, and hair. Arsenic concentrations in drinking-water varied markedly among locations, from <1 to about 200 μg/L. Over a 10-year period, water from the same source in San Antonio de los Cobres fluctuated within 140 and 220 μg/L, with no trend of decreasing concentration. Arsenic concentrations in women's urine (3–900 μg/L, specific weight 1.018 g/mL) highly correlated with concentrations in water on a group level, but showed marked variations between individuals. Arsenic concentrations in hair (range 20–1,500 μg/kg) rather poorly correlated with urinary arsenic, possibly due to external contamination. Thus, arsenic concentration in urine seems to be a better marker of individual arsenic exposure than concentrations in drinking-water and hair. PMID:17366773

Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pei, Qiuling, E-mail: 924969007@qq.com; Ma, Ning; Zhang, Jing

There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosismore » was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic. -- Highlights: ► Male inhabitants were investigated from an As-endemic region of China. ► 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs). ► 8-OHdG staining of PMN nuclei was paralleled by increased debris of cells. ► Oxidative DNA damage of PMNs is associated with arsenic-related skin lesions.« less

THE URINARY BLADDER EXHIBITS A U-SHAPED GENOMIC DOSE-RESPONSE FOLLOWING SHORT- AND LONG-TERM EXPOSURE OF MICE TO ARSENATE IN DRINKING WATER

EPA Science Inventory

A number of studies have demonstrated increased urinary bladder tumor incidence in populations exposed to inorganic arsenic in drinking water at concentrations on the order of several hundred micrograms per liter, but experimental animal studies at much higher concentrations have...

Benchmark Dose Modeling Estimates of the Concentrations of Inorganic Arsenic That Induce Changes to the Neonatal Transcriptome, Proteome, and Epigenome in a Pregnancy Cohort.

PubMed

Rager, Julia E; Auerbach, Scott S; Chappell, Grace A; Martin, Elizabeth; Thompson, Chad M; Fry, Rebecca C

2017-10-16

Prenatal inorganic arsenic (iAs) exposure influences the expression of critical genes and proteins associated with adverse outcomes in newborns, in part through epigenetic mediators. The doses at which these genomic and epigenomic changes occur have yet to be evaluated in the context of dose-response modeling. The goal of the present study was to estimate iAs doses that correspond to changes in transcriptomic, proteomic, epigenomic, and integrated multi-omic signatures in human cord blood through benchmark dose (BMD) modeling. Genome-wide DNA methylation, microRNA expression, mRNA expression, and protein expression levels in cord blood were modeled against total urinary arsenic (U-tAs) levels from pregnant women exposed to varying levels of iAs. Dose-response relationships were modeled in BMDExpress, and BMDs representing 10% response levels were estimated. Overall, DNA methylation changes were estimated to occur at lower exposure concentrations in comparison to other molecular endpoints. Multi-omic module eigengenes were derived through weighted gene co-expression network analysis, representing co-modulated signatures across transcriptomic, proteomic, and epigenomic profiles. One module eigengene was associated with decreased gestational age occurring alongside increased iAs exposure. Genes/proteins within this module eigengene showed enrichment for organismal development, including potassium voltage-gated channel subfamily Q member 1 (KCNQ1), an imprinted gene showing differential methylation and expression in response to iAs. Modeling of this prioritized multi-omic module eigengene resulted in a BMD(BMDL) of 58(45) μg/L U-tAs, which was estimated to correspond to drinking water arsenic concentrations of 51(40) μg/L. Results are in line with epidemiological evidence supporting effects of prenatal iAs occurring at levels <100 μg As/L urine. Together, findings present a variety of BMD measures to estimate doses at which prenatal iAs exposure influences neonatal outcome-relevant transcriptomic, proteomic, and epigenomic profiles.

Arsenic in the human food chain, biotransformation and toxicology--Review focusing on seafood arsenic.

PubMed

Molin, Marianne; Ulven, Stine Marie; Meltzer, Helle Margrete; Alexander, Jan

2015-01-01

Fish and seafood are main contributors of arsenic (As) in the diet. The dominating arsenical is the organoarsenical arsenobetaine (AB), found particularly in finfish. Algae, blue mussels and other filter feeders contain less AB, but more arsenosugars and relatively more inorganic arsenic (iAs), whereas fatty fish contain more arsenolipids. Other compounds present in smaller amounts in seafood include trimethylarsine oxide (TMAO), trimethylarsoniopropionate (TMAP), dimethylarsenate (DMA), methylarsenate (MA) and sulfur-containing arsenicals. The toxic and carcinogenic arsenical iAs is biotransformed in humans and excreted in urine as the carcinogens dimethylarsinate (DMA) and methylarsonate (MA), producing reactive intermediates in the process. Less is known about the biotransformation of organoarsenicals, but new insight indicates that bioconversion of arsenosugars and arsenolipids in seafood results in urinary excretion of DMA, possibly also producing reactive trivalent arsenic intermediates. Recent findings also indicate that the pre-systematic metabolism by colon microbiota play an important role for human metabolism of arsenicals. Processing of seafood may also result in transformation of arsenicals. Copyright © 2015 Elsevier GmbH. All rights reserved.

Blood Pressure Changes in Relation to Arsenic Exposure in a U.S. Pregnancy Cohort

PubMed Central

Farzan, Shohreh F.; Chen, Yu; Wu, Fen; Jiang, Jieying; Liu, Mengling; Baker, Emily; Korrick, Susan A.

2015-01-01

Background Inorganic arsenic exposure has been related to the risk of increased blood pressure based largely on cross-sectional studies conducted in highly exposed populations. Pregnancy is a period of particular vulnerability to environmental insults. However, little is known about the cardiovascular impacts of arsenic exposure during pregnancy. Objectives We evaluated the association between prenatal arsenic exposure and maternal blood pressure over the course of pregnancy in a U.S. population. Methods The New Hampshire Birth Cohort Study is an ongoing prospective cohort study in which > 10% of participant household wells exceed the arsenic maximum contaminant level of 10 μg/L established by the U.S. EPA. Total urinary arsenic measured at 24–28 weeks gestation was measured and used as a biomarker of exposure during pregnancy in 514 pregnant women, 18–45 years of age, who used a private well in their household. Outcomes were repeated blood pressure measurements (systolic, diastolic, and pulse pressure) recorded during pregnancy. Results Using linear mixed effects models, we estimated that, on average, each 5-μg/L increase in urinary arsenic was associated with a 0.15-mmHg (95% CI: 0.02, 0.29; p = 0.022) increase in systolic blood pressure per month and a 0.14-mmHg (95% CI: 0.02, 0.25; p = 0.021) increase in pulse pressure per month over the course of pregnancy. Conclusions In our U.S. cohort of pregnant women, arsenic exposure was associated with greater increases in blood pressure over the course of pregnancy. These findings may have important implications because even modest increases in blood pressure impact cardiovascular disease risk. Citation Farzan SF, Chen Y, Wu F, Jiang J, Liu M, Baker E, Korrick SA, Karagas MR. 2015. Blood pressure changes in relation to arsenic exposure in a U.S. pregnancy cohort. Environ Health Perspect 123:999–1006; http://dx.doi.org/10.1289/ehp.1408472 PMID:25793356

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Songbo; Wu, Jie; Li, Yuanyuan

To investigate the differences in urinary arsenic metabolism patterns of individuals exposed to a high concentration of inorganic arsenic (iAs) in drinking water, an epidemiological investigation was conducted with 155 individuals living in a village where the arsenic concentration in the drinking water was 969 μg/L. Blood and urine samples were collected from 66 individuals including 51 cases with skin lesions and 15 controls without skin lesions. The results showed that monomethylated arsenic (MMA), the percentage of MMA (%MMA) and the ratio of MMA to iAs (MMA/iAs) were significantly increased in patients with skin lesions as compared to controls, whilemore » dimethylated arsenic (DMA), the percentage of DMA (%DMA) and the ratio of DMA to MMA (DMA/MMA) were significantly reduced. The percent DMA of individuals with the Ala/Asp genotype of glutathione S-transferase omega 1 (GSTO1) was significantly lower than those with Ala/Ala. The percent MMA of individuals with the A2B/A2B genotype of arsenic (+ 3 oxidation state) methyltransferase (AS3MT) was significantly lower than those with AB/A2B. The iAs and total arsenic (tAs) content in the urine of a Tibetan population were significantly higher than that of Han and Hui ethnicities, whereas MMA/iAs was significantly lower than that of Han and Hui ethnicities. Our results showed that when exposed to the same arsenic environment, different individuals exhibited different urinary arsenic metabolism patterns. Gender and ethnicity affect these differences and above polymorphisms may be effectors too. - Highlights: • We first survey a village with high iAs content in the drinking water (969 μg/L). • 90 villagers suffered typical skin lesions with a morbidity rate of 58%. • Cases exhibited higher %MMA and MMA/iAs, and lower %DMA and DMA/MMA than controls. • Gender and ethnicity affect the differences of iAs methylation metabolism levels. • GSTO1 and AS3MT gene polymorphisms may be factors too.« less

INDUCTION OF URINARY BLADDER PATHOLOGY IN MALE AND FEMALE C3H MICE EXPOSED TO SODIUM ARSENITE FROM GESTATION THROUGH YOUNG ADULTHOOD

EPA Science Inventory

Epidemiology studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Recently, an in utero animal model was developed to characterize the carcinogenic properties of inorganic arsen...

Biomonitoring of urinary metals in a population living in the vicinity of industrial sources: a comparison with the general population of Andalusia, Spain.

PubMed

Aguilera, Inmaculada; Daponte, Antonio; Gil, Fernando; Hernández, Antonio F; Godoy, Patricia; Pla, Antonio; Ramos, Juan Luis

2008-12-15

The Ria of Huelva (south-west Spain) is one of the most polluted fluvial-estuarine systems in the world. Industrial activity delivers huge amounts of pollutants to the local environment, particularly heavy metals and arsenic. Here we aimed to determine urinary levels of As, Cd, Cr, Cu and Ni in a representative sample (n=857) of adults living in the Ria of Huelva. Levels were compared to those from a representative sample of 861 adults of the general urban population of Andalusia (southern Spain) and multiple regression models were developed to identify individual factors associated with urinary levels of these elements. Arsenic levels were significantly higher in the Ria of Huelva as compared to other Andalusian cities, whereas Cd and Ni levels were significantly lower. Despite these differences, levels in both groups were similar to the reference values reported in previous studies for general population. Age, gender, diet and lifestyle were the major factors contributing to the interindividual variation in urinary metals. In conclusion, despite living in a highly polluted area, the population of the Ria of Huelva failed to show higher urinary levels of the studied metals as compared to a reference urban population of the same region.

Humans seem to produce arsenobetaine and dimethylarsinate after a bolus dose of seafood.

PubMed

Molin, M; Ulven, S M; Dahl, L; Telle-Hansen, V H; Holck, M; Skjegstad, G; Ledsaak, O; Sloth, J J; Goessler, W; Oshaug, A; Alexander, J; Fliegel, D; Ydersbond, T A; Meltzer, H M

2012-01-01

Seafood is the predominant food source of several organoarsenic compounds. Some seafood species, like crustaceans and seaweed, also contain inorganic arsenic (iAs), a well-known toxicant. It is unclear whether human biotransformation of ingested organoarsenicals from seafood result in formation of arsenicals of health concern. The present controlled dietary study examined the urinary excretion of arsenic compounds (total arsenic (tAs), iAs, AB (arsenobetaine), dimethylarsinate (DMA) and methylarsonate (MA)) following ingestion of a single test meal of seafood (cod, 780 μg tAs, farmed salmon, 290 μg tAs or blue mussel, 690 μg tAs or potato (control, 110 μg tAs)) in 38 volunteers. The amount of ingested tAs excreted via the urine within 0-72 h varied significantly among the groups: Cod, 74% (52-92%), salmon 56% (46-82%), blue mussel 49% (37-78%), control 45% (30-60%). The estimated total urinary excretion of AB was higher than the amount of ingested AB in the blue mussel group (112%) and also ingestion of cod seemed to result in more AB, indicating possible endogenous formation of AB from other organoarsenicals. Excretion of iAs was lower than ingested (13-22% of the ingested iAs was excreted in the different groups). Although the ingested amount of iAs+DMA+MA was low for all seafood groups (1.2-4.5% of tAs ingested), the urinary DMA excretion was high in the blue mussel and salmon groups, counting for 25% and 11% of the excreted tAs respectively. In conclusion our data indicate a possible formation of AB as a result of biotransformation of other organic arsenicals. The considerable amount of DMA excreted is probably not only due to methylation of ingested iAs, but due to biotransformation of organoarsenicals making it an inappropriate biomarker of iAs exposure in populations with a high seafood intake. Copyright © 2011 Elsevier Inc. All rights reserved.

Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka

Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30more » days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased both oxidative and nitrosative stress in thoracic aorta. • Atorvastatin regularized blood pressure, improved lipid profile and restored redox homeostasis.« less

Relation between in Utero Arsenic Exposure and Birth Outcomes in a Cohort of Mothers and Their Newborns from New Hampshire

PubMed Central

Gilbert-Diamond, Diane; Emond, Jennifer A.; Baker, Emily R.; Korrick, Susan A.; Karagas, Margaret R.

2016-01-01

Background: Studies suggest that arsenic exposure influences birth outcomes; however, findings are mixed. Objective: We assessed in utero arsenic exposure in relation to birth outcomes and whether maternal prepregnancy weight and infant sex modified the associations. Methods: Among 706 mother–infant pairs exposed to low levels of arsenic through drinking water and diet, we assessed in utero arsenic exposure using maternal second-trimester urinary arsenic, maternal prepregnancy weight through self-report, and birth outcomes from medical records. Results: Median (interquartile range) of total urinary arsenic [tAs; inorganic arsenic (iAs) + monomethylarsonic acid (MMA) + dimethylarsinic acid (DMA)] was 3.4 μg/L (1.7–6.0). In adjusted linear models, each doubling of tAs was associated with a 0.10-cm decrease (95% CI: –0.19, –0.01) in head circumference. Results were similar for MMA and DMA. Ln(tAs) and ln(DMA) were positively associated with birth length in infant males only; among males, each doubling of tAs was associated with a 0.28-cm increase (95% CI: 0.09, 0.46) in birth length (pinteraction = 0.04). Results were similar for DMA. Additionally, arsenic exposure was inversely related to ponderal index, and associations differed by maternal weight. Each ln(tAs) doubling of tAs was associated with a 0.55-kg/m3 lower (95% CI: –0.82, –0.28, p < 0.001) ponderal index for infants of overweight/obese, but not normal-weight, mothers (pinteraction < 0.01). Finally, there was a significant interaction between maternal weight status, infant sex, and arsenic exposure on birth weight (pinteraction = 0.03). In girls born of overweight/obese mothers, each doubling of tAs was associated with a 62.9-g decrease (95% CI: –111.6, –14.2) in birth weight, though the association was null in the other strata. Conclusions: Low-level arsenic exposure may affect fetal growth, and the associations may be modified by maternal weight status and infant sex. Citation: Gilbert-Diamond D, Emond JA, Baker ER, Korrick SA, Karagas MR. 2016. Relation between in utero arsenic exposure and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environ Health Perspect 124:1299–1307; http://dx.doi.org/10.1289/ehp.1510065 PMID:26955061

Relation between in Utero Arsenic Exposure and Birth Outcomes in a Cohort of Mothers and Their Newborns from New Hampshire.

PubMed

Gilbert-Diamond, Diane; Emond, Jennifer A; Baker, Emily R; Korrick, Susan A; Karagas, Margaret R

2016-08-01

Studies suggest that arsenic exposure influences birth outcomes; however, findings are mixed. We assessed in utero arsenic exposure in relation to birth outcomes and whether maternal prepregnancy weight and infant sex modified the associations. Among 706 mother-infant pairs exposed to low levels of arsenic through drinking water and diet, we assessed in utero arsenic exposure using maternal second-trimester urinary arsenic, maternal prepregnancy weight through self-report, and birth outcomes from medical records. Median (interquartile range) of total urinary arsenic [tAs; inorganic arsenic (iAs) + monomethylarsonic acid (MMA) + dimethylarsinic acid (DMA)] was 3.4 μg/L (1.7-6.0). In adjusted linear models, each doubling of tAs was associated with a 0.10-cm decrease (95% CI: -0.19, -0.01) in head circumference. Results were similar for MMA and DMA. Ln(tAs) and ln(DMA) were positively associated with birth length in infant males only; among males, each doubling of tAs was associated with a 0.28-cm increase (95% CI: 0.09, 0.46) in birth length (pinteraction = 0.04). Results were similar for DMA. Additionally, arsenic exposure was inversely related to ponderal index, and associations differed by maternal weight. Each ln(tAs) doubling of tAs was associated with a 0.55-kg/m3 lower (95% CI: -0.82, -0.28, p < 0.001) ponderal index for infants of overweight/obese, but not normal-weight, mothers (pinteraction < 0.01). Finally, there was a significant interaction between maternal weight status, infant sex, and arsenic exposure on birth weight (pinteraction = 0.03). In girls born of overweight/obese mothers, each doubling of tAs was associated with a 62.9-g decrease (95% CI: -111.6, -14.2) in birth weight, though the association was null in the other strata. Low-level arsenic exposure may affect fetal growth, and the associations may be modified by maternal weight status and infant sex. Gilbert-Diamond D, Emond JA, Baker ER, Korrick SA, Karagas MR. 2016. Relation between in utero arsenic exposure and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environ Health Perspect 124:1299-1307; http://dx.doi.org/10.1289/ehp.1510065.

Biological monitoring and the influence of genetic polymorphism of As3MT and GSTs on distribution of urinary arsenic species in occupational exposure workers.

PubMed

Janasik, Beata; Reszka, Edyta; Stanislawska, Magdalena; Wieczorek, Edyta; Fendler, Wojciech; Wasowicz, Wojciech

2015-08-01

To examine the differences in urinary arsenic metabolism patterns in men affected by occupational exposure, we performed a study on 149 participants—workers of a copper mill and 52 healthy controls without occupational exposure. To elucidate the role of genetic factors in arsenic (As) metabolism, we studied the associations of six polymorphisms: As3MT Met287Thr (T>C) in exon 9; As3MT A>G in 5'UTR; As3MT C>G in intron 6; As3MT T>G in intron 1; GSTP1 Ile105Val and GSTO2 T>C. Air samples were collected using individual samplers during work shift. Urine samples were analyzed for total arsenic and arsenic chemical forms (As(III); As(V), MMA, DMA, AsB) using HPLC-ICP-MS. A specific polymerase chain reaction was done for the amplification of exons and flanking regions of As3MT and GSTs. The geometric mean arsenic concentrations in the air were 27.6 ± 4.9 µg/m(3). A significant correlation (p < 0.05) was observed between arsenic in air and sum of iAs +MMA and iAs. As3MT (rs3740400) GG homozygotes showed significantly (p < 0.05) higher %iAs (21.8 ± 2.0) in urine than GC+CC heterozygotes (16.0 ± 2.1). A strong association between the gene variants and As species in urine was observed for GSTO2 (rs156697) polymorphism. The findings of the study point out that the concentration of iAs or the sum of iAs + MMA in urine can be a reliable biological indicator of occupational exposure to arsenic. This study demonstrates that As3MT and/or GSTs genotype may influence As metabolism. Nevertheless, further studies investigating genetic polymorphism in occupational conditions are required.

Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua, Mexico.

PubMed

Mendez, Michelle A; González-Horta, Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Cerón, Roberto Hernández; Morales, Damián Viniegra; Terrazas, Francisco A Baeza; Ishida, María C; Gutiérrez-Torres, Daniela S; Saunders, R Jesse; Drobná, Zuzana; Fry, Rebecca C; Buse, John B; Loomis, Dana; García-Vargas, Gonzalo G; Del Razo, Luz M; Stýblo, Miroslav

2016-01-01

Exposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures. This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk. We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008-2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine. After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine. Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol. Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104-111; http://dx.doi.org/10.1289/ehp.1408742.

Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua, Mexico

PubMed Central

Mendez, Michelle A.; González-Horta, Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Cerón, Roberto Hernández; Morales, Damián Viniegra; Terrazas, Francisco A. Baeza; Ishida, María C.; Gutiérrez-Torres, Daniela S.; Saunders, R. Jesse; Drobná, Zuzana; Fry, Rebecca C.; Buse, John B.; Loomis, Dana; García-Vargas, Gonzalo G.; Del Razo, Luz M.

2015-01-01

Background Exposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures. Objective This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk. Methods We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008–2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine. Results After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine. Conclusions Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol. Citation Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104–111; http://dx.doi.org/10.1289/ehp.1408742 PMID:26068977

Carotid Intima-Media Thickness and Plasma Asymmetric Dimethylarginine in Mexican Children Exposed to Inorganic Arsenic

PubMed Central

Osorio-Yáñez, Citlalli; Ayllon-Vergara, Julio C.; Aguilar-Madrid, Guadalupe; Arreola-Mendoza, Laura; Hernández-Castellanos, Erika; Barrera-Hernández, Angel; De Vizcaya-Ruiz, Andrea

2013-01-01

Background: Arsenic exposure is a risk factor for atherosclerosis in adults, but there is little information on arsenic and early risk biomarkers for atherosclerosis in children. Carotid intima-media thickness (cIMT) is an indicator of subclinical atherosclerotic burden that has been associated with plasma asymmetric dimethylarginine (ADMA), a predictor of cardiovascular disease risk. Objectives: The aim of this study was to investigate associations of arsenic exposure with cIMT, ADMA, and endothelial adhesion molecules [soluble intercellular cell adhesion molecule-1 (sICAM-1); soluble vascular cell adhesion molecule-1 (sVCAM-1)] in children who had been exposed to environmental inorganic arsenic (iAs). Methods: We conducted a cross-sectional study in 199 children 3–14 years of age who were residents of Zimapan, México. We evaluated cIMT using ultrasonography, and plasma lipid profiles by standard methods. We analyzed ADMA, sICAM-1, and sVCAM-1 by ELISA, and measured the concentrations of total speciated arsenic (tAs) in urine using hydride generation cryotrapping atomic absorption spectrometry. Results: In the multiple linear regression model for cIMT, tAs categories were positively associated with cIMT increase. The estimated cIMT diameter was greater in 35- to 70-ng/mL and > 70-ng/mL groups (0.035 mm and 0.058 mm per 1-ng/mL increase in urinary tAs, respectively), compared with the < 35-ng/mL group. In addition to tAs level, plasma ADMA was a significant predictor of cIMT. In the adjusted regression model, cIMT, percent iAs, and plasma sVCAM-1 were significant predictors of ADMA levels (e.g., 0.419-μmol/L increase in ADMA per 1-mm increase in cIMT). Conclusions: Arsenic exposure and plasma ADMA levels were positively associated with cIMT in a population of Mexican children with environmental arsenic exposure through drinking water. Citation: Osorio-Yáñez C, Ayllon-Vergara JC, Aguilar-Madrid G, Arreola-Mendoza L, Hernández-Castellanos E, Barrera-Hernández A, De Vizcaya-Ruíz A, Del Razo LM. 2013. Carotid intima-media thickness and plasma asymmetric dimethylarginine in Mexican children exposed to inorganic arsenic. Environ Health Perspect 121:1090–1096; http://dx.doi.org/10.1289/ehp.1205994 PMID:23757599

Use status and metabolism of realgar in Chinese patent medicine.

PubMed

Li, Yongfang; Wang, Da; Xu, Yuanyuan; Liu, Boying; Zheng, Yi; Yang, Boyi; Fan, Shujun; Zhi, Xueyuan; Zheng, Quanmei; Sun, Guifan

2015-04-08

Realgar is widely used in combination with other herbs as Chinese patent medicine to treat a wide range of diseases in China. It is also a well known arsenical toxicant. Chronic arsenic poisoning events caused by long-term usage of realgar-containing medicines have been reported in literatures. Given to the paradoxical role of realgar, comprehensive outline of its usage status in Chinese patent medicine might provide basal data for evaluating its toxicology risks in populations. Unfortunately, the relevant information is limited. Also, a metabolic process after intake of realgar-containing medicine in humans is poorly understood. The Traditional Chinese Patent Medicine Prescription Database was reviewed to get the information on the usage status of realgar. Realgar powder was dissolved in different pH-value solutions (1, 3, 5, 7, 9 and 11) to determine the soluble arsenic concentrations from realgar. Ten volunteers aged 24-26 years old were recruited to take four pills of Niu Huang Jie Du Pian (NHJDP), a very common Chinese patent medicine with realgar, to analyze the arsenic metabolism after exposure to realgar-containing medicine. The four pills were taken according to the medical instruction. Concentrations of soluble arsenic from realgar and urinary arsenic metabolites in humans were determined by hydride generation atomic absorption spectrometry. A total of 191 (2.25%) realgar-containing traditional Chinese patent medicines were obtained from the database, and almost 86.91% of them were for oral application. 73 (38.22%) medicines were found to be available for children. The mass fraction of arsenic in realgar-containing medicine ranged from 0.11% to 27.52%. According to medical instructions, the amount of average daily arsenic intake ranged from 0.47 to 2895.53mg. Nearly 86% medicines with daily intake of arsenic >10mg. Only inorganic arsenic (iAs) was detected from realgar in dissolution experiment and the levels of soluble iAs increased with pH values. After intake NHJDP, arsenic excretion in urine significantly increased, with a maximum excretion of iAs and monomethylarsonic acid at 6h post-ingestion and a peak excretion of dimethylarsinic acid at 9h post-ingestion. Arsenic methylation capacity was decreased after intake NHJDP. Females carried a more efficient arsenic methylation process than males. Realgar is widely used in traditional Chinese medicine. The arsenic solubility from realgar may be enhanced under alkaline conditions. The levels of urinary arsenic metabolites significantly increased while the arsenic methylation capacity significantly decreased after intaking realgar-containing medicine, which may suggest that a potential health hazard exists if people use arsenical medicines for long-term. Copyright © 2015. Published by Elsevier Ireland Ltd.

The Impact of Hazardous Chemicals on Macrophages

DTIC Science & Technology

2012-04-01

by inducing the activity of phase II detoxification enzymes in the urinary bladder. Arsenic {Ill) chloride [Ars(III)Cl]: Arsenic is one of the...agent used as raw materials for pharmaceuticals, analytical reagent as well as in organic synthesis and making iodine salts. 4,4’-Methylenebis ( 4𔃾...several factors. First, we sought to include hazardous chemicals with properties broadly representative of categories of TICs such as chlorides and

Urinary Arsenic Metabolites in Children and Adults Exposed to Arsenic in Drinking Water in Inner Mongolia, China

PubMed Central

Sun, Guifan; Xu, Yuanyuan; Li, Xin; Jin, Yaping; Li, Bing; Sun, Xiance

2007-01-01

Background We report the concentrations and distributions of urinary arsenic (As) metabolites in 233 residents exposed to 20, 90, or 160 μg/L inorganic arsenic (iAs) in drinking water from three villages in Hohhot, Inner Mongolia, China, that formed one control and two exposed groups. Methods We used hydride generation-atomic absorption spectrometry (HGAAS) to determine iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). Results The concentrations of each urinary As species in the two exposed groups were significantly higher than in the control group for both children and adults. Both children and adults in exposed groups had higher percent iAs and MMA and lower percent DMA, and low primary and secondary methylation indices (PMI and SMI, respectively) than those in the control group. However, children showed significant increases in percent DMA and the SMI as well as decreases in the percent MMA when the iAs exposure level increased from 90 to 160 μg/L. In addition, children in the two exposed groups showed lower percent MMA but higher percent DMA and higher SMI than adults in the same exposed group. No significant differences in As metabolite concentrations and distributions were found between males and females in each group. A significant correlation was also found in the SMI between 11 pairs of children and their mothers from the 160-μg/L–exposed group. Conclusions Children had higher a capacity for secondary methylation of As than adults when exposed to the same concentrations of iAs in drinking water. Exposure to As may increase the capacity for methylation in children to some extent. PMID:17450238

Biological monitoring of occupational exposure to inorganic arsenic

PubMed Central

Apostoli, P.; Bartoli, D.; Alessio, L.; Buchet, J. P.

1999-01-01

OBJECTIVES: This study was undertaken to assess reliable biological indicators for monitoring the occupational exposure to inorganic arsenic (iAs), taking into account the possible confounding role of arsenicals present in food and of the element present in drinking water. METHODS: 51 Glass workers exposed to As trioxide were monitored by measuring dust in the breathing zone, with personal air samplers. Urine samples at the end of work shift were analysed for biological monitoring. A control group of 39 subjects not exposed to As, and eight volunteers who drank water containing about 45 micrograms/l iAs for a week were also considered. Plasma mass spectrometry (ICP-MS) was used for the analysis of total As in air and urine samples, whereas the urinary As species (trivalent, As3; pentavalent, As5; monomethyl arsonic acid, MMA; dimethyl arsinic acid, DMA; arsenobetaine, AsB) were measured by liquid chromatography coupled with plasma mass spectrometry (HPLC-MS) RESULTS: Environmental concentrations of As in air varied widely (mean 84 micrograms/m3, SD 61, median 40) and also the sum of urinary iAs MMA and DMA, varied among the groups of exposed subjects (mean 106 micrograms/l, SD 84, median 65). AsB was the most excreted species (34% of total As) followed by DMA (28%), MMA (26%), and As3 + As5 (12%). In the volunteers who drank As in the water the excretion of MMA and DMA increased (from a median of 0.5 to 5 micrograms/day for MMA and from 4 to 13 micrograms/day for DMA). The best correlations between As in air and its urinary species were found for total iAs and As3 + As5. CONCLUSIONS: To avoid the effect of As from sources other than occupation on urinary species of the element, in particular on DMA, it is proposed that urinary As3 + As5 may an indicator for monitoring the exposure to iAs. For concentrations of 10 micrograms/m3 the current environmental limit for iAs, the limit for urinary As3 + As5 was calculated to be around 5 micrograms/l, even if the wide variation of values needs critical evaluation and application of data. The choice of this indicator might be relevant also from a toxicological point of view. Trivalent arsenic is in fact the most active species and its measure in urine could be the best indicator of some critical effects of the element, such as cancer.   PMID:10658539

Biological monitoring of occupational exposure to inorganic arsenic.

PubMed

Apostoli, P; Bartoli, D; Alessio, L; Buchet, J P

1999-12-01

This study was undertaken to assess reliable biological indicators for monitoring the occupational exposure to inorganic arsenic (iAs), taking into account the possible confounding role of arsenicals present in food and of the element present in drinking water. 51 Glass workers exposed to As trioxide were monitored by measuring dust in the breathing zone, with personal air samplers. Urine samples at the end of work shift were analysed for biological monitoring. A control group of 39 subjects not exposed to As, and eight volunteers who drank water containing about 45 micrograms/l iAs for a week were also considered. Plasma mass spectrometry (ICP-MS) was used for the analysis of total As in air and urine samples, whereas the urinary As species (trivalent, As3; pentavalent, As5; monomethyl arsonic acid, MMA; dimethyl arsinic acid, DMA; arsenobetaine, AsB) were measured by liquid chromatography coupled with plasma mass spectrometry (HPLC-MS) RESULTS: Environmental concentrations of As in air varied widely (mean 84 micrograms/m3, SD 61, median 40) and also the sum of urinary iAs MMA and DMA, varied among the groups of exposed subjects (mean 106 micrograms/l, SD 84, median 65). AsB was the most excreted species (34% of total As) followed by DMA (28%), MMA (26%), and As3 + As5 (12%). In the volunteers who drank As in the water the excretion of MMA and DMA increased (from a median of 0.5 to 5 micrograms/day for MMA and from 4 to 13 micrograms/day for DMA). The best correlations between As in air and its urinary species were found for total iAs and As3 + As5. To avoid the effect of As from sources other than occupation on urinary species of the element, in particular on DMA, it is proposed that urinary As3 + As5 may an indicator for monitoring the exposure to iAs. For concentrations of 10 micrograms/m3 the current environmental limit for iAs, the limit for urinary As3 + As5 was calculated to be around 5 micrograms/l, even if the wide variation of values needs critical evaluation and application of data. The choice of this indicator might be relevant also from a toxicological point of view. Trivalent arsenic is in fact the most active species and its measure in urine could be the best indicator of some critical effects of the element, such as cancer.

Arsenic methylation capacity is associated with breast cancer in northern Mexico.

PubMed

López-Carrillo, Lizbeth; Hernández-Ramírez, Raúl Ulises; Gandolfi, A Jay; Ornelas-Aguirre, José Manuel; Torres-Sánchez, Luisa; Cebrian, Mariano E

2014-10-01

Exposure to environmental contaminants, dietary factors and lifestyles may explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs) in the drinking water is a concern in many regions, such as northern Mexico. Studies in several countries have associated the proportion of urinary monomethylarsenic (%MMA) with increased risks for many As-related diseases, including cancer. To investigate the potential relationships between the risk of BC and the capacity to methylate iAs, a hospital-based case-control study (1016 cases/1028 controls) was performed in northern Mexico. Women were directly interviewed about their reproductive histories. The profile of As metabolites in urine was determined by HPLC-ICP-MS and methylation capacity was assessed by metabolite percentages and indexes. Total urinary As, excluding arsenobetaine (TAs-AsB), ranged from 0.26 to 303.29μg/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35μg/L). Women with higher %MMA and/or primary methylation index (PMI) had an increased BC risk (%MMA ORQ5vs.Q1=2.63; 95%CI 1.89,3.66; p for trend <0.001; PMI ORQ5vs.Q1=1.90; 95%CI 1.39,2.59, p for trend <0.001). In contrast, women with higher proportion of urinary dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC risk (%DMA ORQ5vs.Q1=0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI ORQ5vsQ1=0.42, 95%CI 0.31,0.59, p for trend <0.001). Neither %iAs nor total methylation index was associated to BC risk. Inter-individual variations in iAs metabolism may play a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA and/or a lower capacity to further methylate MMA to DMA were at higher BC risk. Copyright © 2014 Elsevier Inc. All rights reserved.

Arsenate Impact on the Metabolite Profile, Production, and Arsenic Loading of Xylem Sap in Cucumbers (Cucumis sativus L.)

PubMed Central

Uroic, M. Kalle; Salaün, Pascal; Raab, Andrea; Feldmann, Jörg

2012-01-01

Arsenic uptake and translocation studies on xylem sap focus generally on the concentration and speciation of arsenic in the xylem. Arsenic impact on the xylem sap metabolite profile and its production during short term exposure has not been reported in detail. To investigate this, cucumbers were grown hydroponically and arsenate (AsV) and DMA were used for plant treatment for 24 h. Total arsenic and arsenic speciation in xylem sap was analyzed including a metabolite profiling under AsV stress. Produced xylem sap was quantified and absolute arsenic transported was determined. AsV exposure had a significant impact on the metabolite profile of xylem sap. Four m/z values corresponding to four compounds were up-regulated, one compound down-regulated by AsV exposure. The compound down-regulated was identified to be isoleucine. Furthermore, AsV exposure had a significant influence on sap production, leading to a reduction of up to 96% sap production when plants were exposed to 1000 μg kg−1 AsV. No difference to control plants was observed when plants were exposed to 1000 μg kg−1 DMA. Absolute arsenic amount in xylem sap was the lowest at high AsV exposure. These results show that AsV has a significant impact on the production and metabolite profile of xylem sap. The physiological importance of isoleucine needs further attention. PMID:22536187

Human arsenic poisoning issues in central-east Indian locations: biomarkers and biochemical monitoring.

PubMed

Pandey, Piyush Kant; Yadav, Sushma; Pandey, Madhurima

2007-03-01

The study reports the use of three biomarkers i.e. total arsenic in hair and nails, total arsenic in blood, and total arsenic in urine to identify or quantify arsenic exposure and concomitant health effects. The main source of arsenic was inorganic exposure through drinking water. The arsenic levels and the health effects were analyzed closely in a family having maximum symptoms of arsenic. Based on the result of this study it is reported that there exist a correlation between the clinically observable symptoms, the blood and urine arsenic level, and the arsenic intake through drinking water. An intensive study on the urinary arsenic levels was carried out in which the urine levels of arsenic and the urine sufficiency tests were performed. A composite picture of body burden of arsenic has been obtained by carrying out a complete biochemical analysis of a maximum affected family. This confirms pronounced chronic exposure of the arsenic to these people. A combined correlation study on the arsenic levels measured in whole blood, urine, hair, nails and age present a remarkable outcome. Accordingly, the arsenic levels in blood are negatively correlated with the urine arsenic levels, which indicate either the inadequacy of the renal system in cleaning the blood arsenic or a continuous recirculation of the accumulated arsenic. This is an important conclusion about arsenical metabolism in humans. The study also raises the issues of the prospects of complete elimination of the accumulated arsenic and the reversibility of the health effects. Based on the work in Kourikasa village we report that there are very remote chances of complete purging of arsenic and thus reversibility of the health effects owing to various factors. The paper also discusses the various issues concerning the chronic arsenic poisoning management in the affected locations.

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1.

PubMed

Cárdenas-González, M; Osorio-Yáñez, C; Gaspar-Ramírez, O; Pavković, M; Ochoa-Martínez, A; López-Ventura, D; Medeiros, M; Barbier, O C; Pérez-Maldonado, I N; Sabbisetti, V S; Bonventre, J V; Vaidya, V S

2016-10-01

Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. Copyright © 2016 Elsevier Inc. All rights reserved.

Dose-dependent urinary phenotype of inorganic arsenic methylation in mice with a focus on trivalent methylated metabolites.

PubMed

García-Montalvo, Eliud A; Valenzuela, Olga L; Sánchez-Peña, Luz C; Albores, Arnulfo; Del Razo, Luz M

2011-11-01

Inorganic arsenic (iAs) exposure has been associated with the increased risk of various forms of cancer and of non-cancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. However, in vivo research involving the production of MAsIII and DMAsIII remains an area of ongoing investigation and debate. The results of metabolic and toxicity studies using mice have been entirely applicable to other species including humans. The goal of this study was to investigate the phenotype for the trivalent and pentavalent arsenic metabolites in relation to arsenite dose via immediate analysis of fresh urine samples, while preventing the oxidation of unstable methylated AsIII-containing metabolites. Female mice (C57BL/6) received sodium arsenite by gavage at doses of 0, 3, 6 or 10 mg As/kg/day for 9 days, after which trivalent methylated arsenicals were detected in 100% of urine samples; these arsenicals were not detected in the urine of control mice. The amount of DMAsIII detected in urine depended on the dose of arsenite administered and was determined to be 50.2%, 31.4% and 16.5% of the total urinary arsenic in mice exposed to 3, 6, or 10 mg/kg/day, respectively. This relationship is consistent with the hypothesis of inhibition or saturation of iAs methylation. Understanding the in vivo production of MAsIII and DMAsIII in mice exposed to iAs could aid in developing a biologically based dose-response model for iAs.

Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico

PubMed Central

Gomez-Rubio, Paulina; Klimentidis, Yann C.; Cantu-Soto, Ernesto; Meza-Montenegro, Maria M.; Billheimer, Dean; Lu, Zhenqiang; Chen, Zhao; Klimecki, Walter T.

2013-01-01

Many studies provide evidence relating lower human arsenic (As) methylation efficiency, represented by high % urinary monomethylarsonic acid (MMA(V)), with several arsenic-induced diseases, possibly due to the fact that MMA(V) serves as a proxy for MMA(III), the most toxic arsenic metabolite. Some epidemiological studies have suggested that indigenous Americans (AME) methylate As more efficiently, however data supporting this have been equivocal. The aim of this study was to characterize the association between AME ancestry and arsenic methylation efficiency using a panel of ancestry informative genetic markers to determine individual ancestry proportions in an admixed population (composed of two or more isolated ancestral populations) of 746 individuals environmentally exposed to arsenic in northwest Mexico. Total urinary As (TAs) mean and range were 170.4 and 2.3–1053.5 μg/L, while %AME mean and range were 72.4 and 23–100. Adjusted (gender, age, AS3MT 7388/M287T haplotypes, body mass index (BMI), and TAs) multiple regression model showed that higher AME ancestry is associated with lower %uMMA excretion in this population (p <0.01). The data also showed a significant interaction between BMI and gender indicating negative association between BMI and %uMMA, stronger in women than men (p <0.01). Moreover age and the AS3MT variants 7388 (intronic) and M287T (non-synonymous) were also significantly associated with As methylation efficiency (p = 0.01). This study highlights the importance of BMI and indigenous American ancestry in some of the observed variability in As methylation efficiency, underscoring the need to be considered in epidemiology studies, particularly those carried out in admixed populations. PMID:22047162

Environmental Exposure to Arsenic and Chromium in Children is Associated with Kidney Injury Molecule-1

PubMed Central

Cárdenas-González, M; Osorio-Yáñez, C; Gaspar-Ramírez, O; Pavković, M; Ochoa-Martínez, A; López-Ventura, D; Medeiros, M; Barbier, OC; Pérez-Maldonado, IN; Sabbisetti, VS; Bonventre, JV; Vaidya, VS

2016-01-01

Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of environmental kidney toxicants exposure and kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6 ppb) and chromium (61.7 ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467 pg/mL; T3: 615 pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μL) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372 pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker for environmental exposure risk assessment and kidney toxicity in children. PMID:27431456

Specific histone modification responds to arsenic-induced oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Lu

To explore whether specific histone modifications are associated with arsenic-induced oxidative damage, we recruited 138 arsenic-exposed and arsenicosis subjects from Jiaole Village, Xinren County of Guizhou province, China where the residents were exposed to arsenic from indoor coal burning. 77 villagers from Shang Batian Village that were not exposed to high arsenic coal served as the control group. The concentrations of urine and hair arsenic in the arsenic-exposure group were 2.4-fold and 2.1-fold (all P < 0.001) higher, respectively, than those of the control group. Global histone modifications in human peripheral lymphocytes (PBLCs) were examined by ELISA. The results showedmore » that altered global levels of H3K18ac, H3K9me2, and H3K36me3 correlated with both urinary and hair-arsenic levels of the subjects. Notably, H3K36me3 and H3K18ac modifications were associated with urinary 8-OHdG (H3K36me3: β = 0.16; P = 0.042, H3K18ac: β = − 0.24; P = 0.001). We also found that the modifications of H3K18ac and H3K36me3 were enriched in the promoters of oxidative stress response (OSR) genes in human embryonic kidney (HEK) cells and HaCaT cells, providing evidence that H3K18ac and H3K36me3 modifications mediate transcriptional regulation of OSR genes in response to NaAsO{sub 2} treatment. Particularly, we found that reduced H3K18ac modification correlated with suppressed expression of OSR genes in HEK cells with long term arsenic treatment and in PBLCs of all the subjects. Taken together, we reveal a critical role for specific histone modification in response to arsenic-induced oxidative damage. - Highlights: • H3K18ac, H3K9me2 and H3K36me3 were associated with arsenic exposed levels. • H3K18ac and H3K36me3 were correlated with oxidative damage induced by arsenic. • H3K18ac and H3K36me3 might involve in transcriptional regulation of OSR genes. • Dysregulation of H3K18ac and H3K36me3 might be biomarkers of arsenic toxicity.« less

Speciation of arsenic in exfoliated urinary bladder epithelial cells from individuals exposed to arsenic in drinking water.

PubMed

Hernández-Zavala, Araceli; Valenzuela, Olga L; Matousek, Tomás; Drobná, Zuzana; Dĕdina, Jirí; García-Vargas, Gonzalo G; Thomas, David J; Del Razo, Luz M; Stýblo, Miroslav

2008-12-01

The concentration of arsenic in urine has been used as a marker of exposure to inorganic As (iAs). Relative proportions of urinary metabolites of iAs have been identified as potential biomarkers of susceptibility to iAs toxicity. However, the adverse effects of iAs exposure are ultimately determined by the concentrations of iAs metabolites in target tissues. In this study we examined the feasibility of analyzing As species in cells that originate in the urinary bladder, a target organ for As-induced cancer in humans. Exfoliated bladder epithelial cells (BECs) were collected from urine of 21 residents of Zimapan, Mexico, who were exposed to iAs in drinking water. We determined concentrations of iAs, methyl-As (MAs), and dimethyl-As (DMAs) in urine using conventional hydride generation-cryotrapping-atomic absorption spectrometry (HG-CT-AAS). We used an optimized HG-CT-AAS technique with detection limits of 12-17 pg As for analysis of As species in BECs. All urine samples and 20 of 21 BEC samples contained detectable concentrations of iAs, MAs, and DMAs. Sums of concentrations of these As species in BECs ranged from 0.18 to 11.4 ng As/mg protein and in urine from 4.8 to 1,947 ng As/mL. We found no correlations between the concentrations or ratios of As species in BECs and in urine. These results suggest that urinary levels of iAs metabolites do not necessarily reflect levels of these metabolites in the bladder epithelium. Thus, analysis of As species in BECs may provide a more effective tool for risk assessment of bladder cancer and other urothelial diseases associated with exposures to iAs.

Bioaccessibility and excretion of arsenic in Niu Huang Jie Du Pian pills

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koch, Iris; Sylvester, Steven; Lai, Vivian W.-M.

2007-08-01

Traditional Chinese medicines (TCMs) often contain significant levels of potentially toxic elements, including arsenic. Niu Huang Jie Du Pian pills were analyzed to determine the concentration, bioaccessibility (arsenic fraction soluble in the human gastrointestinal system) and chemical form (speciation) of arsenic. Arsenic excretion in urine (including speciation) and facial hair were studied after a one-time ingestion. The pills contained arsenic in the form of realgar, and although the total arsenic that was present in a single pill was high (28 mg), the low bioaccessibility of this form of arsenic predicted that only 4% of it was available for absorption intomore » the bloodstream (1 mg of arsenic per pill). The species of arsenic that were solubilized were inorganic arsenate (As(V)) and arsenite (As(III)) but DMAA and MMAA were detected in urine. Two urinary arsenic excretion peaks were observed: an initial peak several (4-8) hours after ingestion corresponding to the excretion of predominantly As(III), and a larger peak at 14 h corresponding predominantly to DMAA and MMAA. No methylated As(III) species were observed. Facial hair analysis revealed that arsenic concentrations did not increase significantly as a result of the ingestion. Arsenic is incompletely soluble under human gastrointestinal conditions, and is metabolized from the inorganic to organic forms found in urine. Bioaccessible arsenic is comparable to the quantity excreted. Facial hair as a bio-indicator should be further tested.« less

Relationship between arsenic skin lesions and the age of natural menopause.

PubMed

Yunus, Fakir Md; Rahman, Musarrat Jabeen; Alam, Md Zahidul; Hore, Samar Kumar; Rahman, Mahfuzar

2014-05-02

Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women's reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh. We compared menopausal age in two groups of women--with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies--participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women. Women with arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups' age at menopause was 2.1 years earlier (p <0.001) for respondents with arsenic skin lesions. The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure.

The Investigation of Unexpected Arsenic Compounds Observed in Routine Biological Monitoring Urinary Speciation Analysis

PubMed Central

Leese, Elizabeth; Clench, Malcolm; Morton, Jackie; Gardiner, Philip H.E.; Carolan, Vikki A.

2017-01-01

This study investigates the identity of two unexpected arsenic species found separately in a number of urine samples sent to the Health and Safety Executive’s Health and Safety Laboratory for arsenic speciation (arsenobetaine, AB; arsenite, As3+; arsenate, As5+; monomethylarsonic acid, MMA5+; and dimethylarsinic acid, DMA5+). Micro liquid chromatography coupled to inductively coupled plasma mass spectrometry (µLC-ICP-MS) and electrospray time of flight tandem mass spectrometry (ESI-QqTOF-MS/MS) were used to identify the two arsenic peaks by comparison to several characterized arsenicals: arsenocholine, AC; trimethyl arsine oxide, TMAO; dimethylarsenoacetate, DMAA; dimethylarsenoethanol, DMAE; thio-dimethylarsinate, thio-DMA; thio-dimethylarsenoacetate, thio-DMAA and thio-dimethylarsenoethanol, thio-DMAE. The results from both the ICP-MS and ESI-QqTOF-MS/MS investigations indicate that the unexpected arsenic species termed peak 1 was thio-DMA. While the unexpected arsenic species termed peak 2 has yet to be identified, this investigation shows that it was not AC, TMAO, DMAA, DMAE, thio-DMA, thio-DMAA or thio-DMAE. This study demonstrates the incidence of unexpected arsenic species in both routine and non-routine urine samples from both workers and hospital patients. PMID:29051444

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

PubMed Central

Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Alba, Cesar Gonzalez-De; Froines, John R.; Espinosa-Fematt, Jorge A.

2016-01-01

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero is associated with an increase in respiratory symptoms and diseases in adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that exposure to arsenic during early childhood or in utero was associated with impairment in the lung function in children and suggested that this adverse effect could be due to a chronic inflammatory response to the metalloid. Therefore, a cross-sectional study was designed in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their As levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the Soluble Receptor for Advanced Glycation Endproducts (sRAGE) sputum level was significantly lower and Matrix Metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsenic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/Tissue Inhibitor of Metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. PMID:26048584

Low-to-Moderate Arsenic Exposure and Respiratory Health in American Indian Communities.

PubMed

Powers, Martha; Sanchez, Tiffany R; Grau-Perez, Maria; Yeh, Fawn; Francesconi, Kevin; Goessler, Walter; George, Christine M; Heaney, Christopher; Best, Lyle G; Umans, Jason; Brown, Robert H; Navas-Acien, Ana

2018-04-01

Exposure to inorganic arsenic, through drinking naturally-contaminated water, is an established cause of lung cancer. Evidence on the impact of arsenic exposure on lung function, however, is less conclusive. The evidence available, mostly from populations exposed to water arsenic levels >100 μg/L, suggests that arsenic exposure is associated with lower lung function. Prospective studies and studies examining low-to-moderate levels of water arsenic exposure (<50 μg/L) the level relevant for U.S. populations, are very limited. We evaluated the association between chronic low-to-moderate arsenic exposure with lung function and disease in an American Indian population. The Strong Heart Study is a multicenter prospective study of cardiovascular disease and its risk factors among American Indian adults. The present analysis, in 2,166 adults, used urinary arsenic measurements at baseline (1989-1991) and lung symptoms and function assessment by standardized spirometry at the second examination (1993-1995). We evaluated associations between arsenic exposure and airflow obstruction, defined as ratio of forced expiratory volume in 1 second (FEV 1 ) to forced vital capacity (FVC) of less than 0.70, and restrictive pattern, defined as FEV 1 /FVC ratio greater than 0.70 and FVC less than 80% predicted; respiratory symptoms; and self-reported physician diagnosis of nonmalignant respiratory disease. The prevalence of airflow obstruction between 1993 and 1995 was 21.4% (463/2,166); restrictive pattern was 14.5% (314/2,166). Median urinary arsenic concentrations were higher in participants with airflow obstruction (11.0 μg/g creatinine) compared to those without obstruction (9.8 μg/g creatinine), and higher in those with restrictive pattern (12.0 μg/g) compared to those without restrictive pattern (9.4 μg/g). The odds ratio (95% confidence interval) for obstructive and restrictive patterns comparing the 75th to 25th percentile of arsenic was 1.13 (0.96-1.32) and 1.27 (1.01-1.60), respectively, after adjustment for age, sex, education, study site, smoking status, smoking pack-year, estimated glomerular filtration rate, tuberculosis, and body mass index. Emphysema, cough 4-6 times a day, phlegm, and stopping for breath were also positively associated with arsenic. In this American Indian population, exposure to low-to-moderate levels of inorganic arsenic, as measured in urine, was positively associated with restrictive pattern as measured by spirometry, self-reported emphysema diagnosis, self-reported shortness of breath, and more frequent cough and phlegm among those with cough, independent of smoking status. These findings suggest that low-to-moderate arsenic exposure can contribute to nonmalignant lung disease, and may be associated with restrictive lung disease.

Concentration-and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to twelve weeks

EPA Science Inventory

Inorganic arsenic (AsD is a known human bladder carcinogen. The objective of this study was to examine the concentration dependence of the genomic response to ASi in the urinary bladders of mice. C57BL/6J mice were exposed for 1 or 12 weeks to arsenate in drinking water at concen...

Dimethylarsinic acid in drinking water changed the morphology of urinary bladder but not the expression of DNA repair genes of bladder transitional epithelium in F344 rats.

PubMed

Wang, Amy; Wolf, Douglas C; Sen, Banalata; Knapp, Geremy W; Holladay, Steven D; Huckle, William R; Caceci, Thomas; Robertson, John L

2009-06-01

Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In F344 rats, dimethylarsinic acid (DMA[V]) increases transitional cell carcinoma. Arsenic-induced inhibition of DNA repair has been reported in cultured cell lines and in lymphocytes of arsenic-exposed humans, but it has not been studied in urinary bladder. Should inhibition of DNA damage repair in transitional epithelium occur, it may contribute to carcinogenesis or cocarcinogenesis. We investigated morphology and expression of DNA repair genes in F344 rat transitional cells following up to 100 ppm DMA(V) in drinking water for four weeks. Mitochondria were very sensitive to DMA(V), and swollen mitochondria appeared to be the main source of vacuoles in the transitional epithelium. Real-time reverse transcriptase polymerase chain reaction (Real-Time RT PCR) showed the mRNA levels of tested DNA repair genes, ataxia telangectasia mutant (ATM), X-ray repair cross-complementing group 1 (XRCC1), excision repair cross-complementing group 3/xeroderma pigmentosum B (ERCC3/XPB), and DNA polymerase beta (Polbeta), were not altered by DMA(V). These data suggested that either DMA(V) does not affect DNA repair in the bladder or DMA(V) affects DNA repair without affecting baseline mRNA levels of repair genes. The possibility remains that DMA(V) may lower damage-induced increases in repair gene expression or cause post-translational modification of repair enzymes.

The factors influencing urinary arsenic excretion and metabolism of workers in steel and iron smelting foundry.

PubMed

Shuhua, Xi; Qingshan, Sun; Fei, Wang; Shengnan, Liu; Ling, Yan; Lin, Zhang; Yingli, Song; Nan, Yan; Guifan, Sun

2014-01-01

In order to evaluate the degree of arsenic (As) exposure and the factors influencing urinary As excretion and metabolism, 192 workers from a steel and iron smelting plant, with different type of work in production such as roller, steel smelting, iron smelting and metallic charge preparation, were recruited. Information about characteristics of each subject was obtained by questionnaire and inorganic As (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) in urine were determined. The results showed that steel smelters had significantly higher concentrations of DMA and total As (TAs) than rollers and metallic charge preparation workers, and iron and steel smelters had a higher value of primary methylation index and lower proportion of the iAs (iAs%) than rollers and metallic charge preparation workers. In steel smelters, urinary As level exceeded the biological exposure index (BEI) limit for urinary As of 35 μg/l by 65.52%, and higher than metallic charge preparation workers (35.14%). The individuals consumed seafood in recent 3 days had a higher TAs than the individuals without seafood consumption. Multivariate logistic regression analysis showed that different jobs, taken Chinese medicine of bezoar and seafood consumption in recent 3 days were significantly associated with urinary TAs exceeded BEI limit value 35 μg/l. Our results suggest that workers in steel and iron smelting plant had a lower level of As exposure, and seafood consumption and taking Chinese medicine of bezoar also could increase the risk of urinary TAs exceeded BEI limit value.

Whole-house arsenic water treatment provided more effective arsenic exposure reduction than point-of-use water treatment at New Jersey homes with arsenic in well water

PubMed Central

Spayd, Steven E.; Robson, Mark G.; Buckley, Brian T.

2014-01-01

A comparison of the effectiveness of whole house (point-of-entry) and point-of-use arsenic water treatment systems in reducing arsenic exposure from well water was conducted. The non-randomized observational study recruited 49 subjects having elevated arsenic in their residential home well water in New Jersey. The subjects obtained either point-of-entry or point-of-use arsenic water treatment. Prior ingestion exposure to arsenic in well water was calculated by measuring arsenic concentrations in the well water and obtaining water-use histories for each subject, including years of residence with the current well and amount of water consumed from the well per day. A series of urine samples were collected from the subjects, some starting before water treatment was installed and continuing for at least nine months after treatment had begun. Urine samples were analyzed and speciated for inorganic-related arsenic concentrations. A two-phase clearance of inorganic-related arsenic from urine and the likelihood of a significant body burden from chronic exposure to arsenic in drinking water were identified. After nine months of water treatment the adjusted mean of the urinary inorganic-related arsenic concentrations were significantly lower (p < 0.0005) in the point-of-entry treatment group (2.5 μg/g creatinine) than in the point-of-use treatment group (7.2 μg/g creatinine). The results suggest that whole house arsenic water treatment systems provide a more effective reduction of arsenic exposure from well water than that obtained by point-of-use treatment. PMID:24975493

Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer

PubMed Central

Rager, Julia E.; Miller, Sloane; Tulenko, Samantha E.; Smeester, Lisa; Ray, Paul D.; Yosim, Andrew; Currier, Jenna M.; Ishida, María C.; González-Horta, Maria del Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Gutiérrez-Torres, Daniela S.; Drobná, Zuzana; Del Razo, Luz M.; García-Vargas, Gonzalo G.; Kim, William Y.; Zhou, Yi-Hui; Wright, Fred A.; Stýblo, Miroslav; Fry, Rebecca C.

2016-01-01

There is strong epidemiologic evidence linking chronic exposure to inorganic arsenic (iAs) to a myriad of adverse health effects, including cancer of the bladder. The present study set out to identify DNA methylation patterns associated with iAs and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic (As)-induced carcinogenesis. Genome-wide, gene-specific promoter DNA methylation levels were assessed in EUCs from 46 residents of Chihuahua, Mexico, and the relationship was examined between promoter methylation profiles and the intracellular concentrations of total As (tAs) and As species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 As-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas repository. Both the As- and cancer-associated genes are enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer. PMID:26039340

Relationship between arsenic skin lesions and the age of natural menopause

PubMed Central

2014-01-01

Background Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women’s reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh. Methods We compared menopausal age in two groups of women – with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies— participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women. Results Women with arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups’ age at menopause was 2.1 years earlier (p <0.001) for respondents with arsenic skin lesions. Conclusions The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure. PMID:24886424

Influence of dietary selenium on the disposition of arsenate in the female B6C3F{sub 1} mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kenyon, E.M.; Hughes, M.F.; Levander, O.A.

1997-06-27

Interactions between arsenic (As) and selenium (Se) at the metabolic level are multifaceted and complex. These interactions are of practical significance because populations in various parts of the world are simultaneously exposed to inorganic As in drinking water and Se mainly in the diet at varying levels. The primary goal of this study was to investigate whether differing dietary Se status would alter the profile of urinary metabolites or their time course for elimination after exposure to arsenate [As(V)]. Weanling female 86C3F, mice were maintained for 28 d on either a control diet of powdered rodent meal sufficient in Semore » (A 0.2 ppm) or Torula yeast-based (TYB) diets deficient (B, 0.02 ppm Se), sufficient (C, 0.2 ppm Se), or excessive (D, 2.0 ppm Se) in Se; mice then received by oral gavage 5 mg (As)/kg as sodium [{sup 73}As] arsenate. The time course for elimination of total arsenic and metabolites in urine was measured over a 48-h period, and total arsenic was determined in feces and tissues at 48 h. Mice on the Se excess diet excreted a significantly higher percentage of urinary As as inorganic As, with a significantly decreased ratio of organic to inorganic As compared to Se-sufficient mice, suggesting that As methylation was decreased. Mice on the Se-deficient diet appeared to eliminate As(V), arsenite, and dimethylarsinic acid (DMA) in urine more slowly than Se-sufficient mice; however, further studies are required to confirm this finding. Mice on the Se-sufficient meal diet (A) excreted significantly less (by percent) arsenate-derived radioactivity in urine and more in feces compared to mice on the Se-sufficient TYB diet (C), with total elimination being similar for both groups. This indicates that mice on the meal diet absorbed significantly less As(V) than mice on the TYB diet, and this may be due to more fiber or {open_quotes}bulk{close_quotes} in the meal diet. 35 refs., 6 figs., 6 tabs.« less

Sex differences in the reduction of arsenic methylation capacity as a function of urinary total and inorganic arsenic in Mexican children.

PubMed

Torres-Sánchez, Luisa; López-Carrillo, Lizbeth; Rosado, Jorge L; Rodriguez, Valentina M; Vera-Aguilar, Eunice; Kordas, Katarzyna; García-Vargas, Gonzalo G; Cebrian, Mariano E

2016-11-01

Chronic arsenic (As) exposure decreases adult and children's ability to methylate inorganic As (iAs); however, few studies have examined children's sex differences. We measured urinary concentrations of iAs, monomethylarsonic (MMA), and dimethylarsinic (DMA) acids, and calculated the primary (PMI: MMA/iAs) and secondary (SMI: DMA/MMA) methylation capacity indexes in 591 children 6-8 years in Torreón, Mexico. We determined iAs, MMA, and DMA by hydride generation cryotrapping AAS. Lineal regression models estimated associations between methylation capacity and total As (TAs) or iAs. Interactions with sex were tested at p<0.10. Boys had significantly higher TAs levels, (58.4µg/L) than girls (46.2µg/L). We observed negative associations between TAs and PMI (β=-0.039; p<0.18) and SMI (β=-0.08; p=0.002) with significant sex differences; PMI reduction was significant in boys (β=-0.09; p=0.02) but not in girls (β=0.021; p=0.63), p for interaction=0.06. In contrast, SMI reduction was significantly more pronounced in girls. Furthermore, negative associations PMI (β=-0.19; p<0.001) and SMI (β=-0.35; p<0.001) were a function of urinary iAs levels, independently of TAs; however, the reduction in PMI was more pronounced in boys (β=-0.24; p<0.001; girls β=-0.15; p<0.001), p for interaction=0.04. A significant negative association was observed between SMI and iAs levels without significant sex differences. TAs and iAs associations with metabolite percentages were in good agreement with those observed with methylation indexes. Our results suggest that iAs plays an important role in reducing As methylation ability and that significant sex differences are present in As metabolism. These differences merit further investigation to confirm our findings and their potential implications for arsenic toxicity in children. Copyright © 2016 Elsevier Inc. All rights reserved.

Polymorphisms in arsenic(+III oxidation state) methyltransferase (AS3MT) predict gene expression of AS3MT as well as arsenic metabolism.

PubMed

Engström, Karin; Vahter, Marie; Mlakar, Simona Jurkovic; Concha, Gabriela; Nermell, Barbro; Raqib, Rubhana; Cardozo, Alejandro; Broberg, Karin

2011-02-01

Arsenic (As) occurs as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in humans, and the methylation pattern demonstrates large interindividual differences. The fraction of urinary MMA is a marker for susceptibility to As-related diseases. We evaluated the impact of polymorphisms in five methyltransferase genes on As metabolism in two populations, one in South America and one in Southeast Asia. The methyltransferase genes were arsenic(+III oxidation state) methyltransferase (AS3MT), DNA-methyltransferase 1a and 3b (DNMT1a and DNMT3b, respectively), phosphatidylethanolamine N-methyltransferase (PEMT), and betaine-homocysteine methyltransferase (BHMT). AS3MT expression was analyzed in peripheral blood. Subjects were women exposed to As in drinking water in the Argentinean Andes [n = 172; median total urinary As (U-As), 200 µg/L] and in rural Bangladesh (n = 361; U-As, 100 µg/L; all in early pregnancy). Urinary As metabolites were measured by high-pressure liquid chromatography/inductively coupled plasma mass spectrometry. Polymorphisms (n = 22) were genotyped with Sequenom, and AS3MT expression was measured by quantitative real-time polymerase chain reaction using TaqMan expression assays. Six AS3MT polymorphisms were significantly associated with As metabolite patterns in both populations (p ≤ 0.01). The most frequent AS3MT haplotype in Bangladesh was associated with a higher percentage of MMA (%MMA), and the most frequent haplotype in Argentina was associated with a lower %MMA and a higher percentage of DMA. Four polymorphisms in the DNMT genes were associated with metabolite patterns in Bangladesh. Noncoding AS3MT polymorphisms affected gene expression of AS3MT in peripheral blood, demonstrating that one functional impact of AS3MT polymorphisms may be altered levels of gene expression. Polymorphisms in AS3MT significantly predicted As metabolism across these two very different populations, suggesting that AS3MT may have an impact on As metabolite patterns in populations worldwide.

Environmental arsenic exposure of schoolchildren in a former tin mining and smelting community of southern Thailand.

PubMed

Vitayavirasak, Banjong; Rakwong, Kittiya; Chatchawej, Warangkana

2005-01-01

Risk behavior and environmental sources of exposure to arsenic for 10-year-old schoolchildren were studied in a high exposure area and a low exposure area of Ron Phibun Subdistrict, Ron Phibun District, Nakhon Si Thammarat Province and compared to those in a control area. Arsenic concentrations of surface soil, ambient air and drinking water to which subjects in the high exposure group, the low exposure group and the control group were exposed, were significantly different (p < 0.05). Similarly, urinary concentrations of total arsenic and the sum of inorganic arsenic and its metabolites were significantly higher in the study groups than the control group. The arsenic content of locally grown agricultural produce was small with the exception of freshwater snails (Sinotaia ingallsiana). Drinking water and surface soil were found to be the main sources of exposure. The exposure was mediated by the subjects' risk behavior, such as playing with soil and no hand-washing before eating. The estimated cancer risk from arsenic for the schoolchildren in the study area was between 10(-5)-10(-6) which meant that their risk of developing cancer was probable. Measures to reduce the cancer risk are recommended.

Environmental exposure to arsenic and chromium in an industrial area.

PubMed

Vimercati, Luigi; Gatti, Maria F; Gagliardi, Tommaso; Cuccaro, Francesco; De Maria, Luigi; Caputi, Antonio; Quarato, Marco; Baldassarre, Antonio

2017-04-01

Arsenic and chromium are widespread environmental contaminants that affect global health due to their toxicity and carcinogenicity. To date, few studies have investigated exposure to arsenic and chromium in a population residing in a high-risk environmental area. The aim of this study is to evaluate the exposure to arsenic and chromium in the general population with no occupational exposure to these metals, resident in the industrial area of Taranto, Southern Italy, through biological monitoring techniques. We measured the levels of chromium, inorganic arsenic, and methylated metabolites, in the urine samples of 279 subjects residing in Taranto and neighboring areas. Qualified health staff administered a standardized structured questionnaire investigating lifestyle habits and controlling for confounding factors. The biological monitoring data showed high urinary concentrations of both the heavy metals investigated, particularly Cr. On this basis, it will be necessary to carry out an organized environmental monitoring program, taking into consideration all exposure routes so as to correlate the environmental concentrations of these metals with the biomonitoring results.

Association of urinary metal profiles with altered glucose levels and diabetes risk: a population-based study in China.

PubMed

Feng, Wei; Cui, Xiuqing; Liu, Bing; Liu, Chuanyao; Xiao, Yang; Lu, Wei; Guo, Huan; He, Meian; Zhang, Xiaomin; Yuan, Jing; Chen, Weihong; Wu, Tangchun

2015-01-01

Elevated heavy metals and fasting plasma glucose (FPG) levels were both associated with increased risk of cardiovascular diseases. However, studies on the associations of heavy metals and essential elements with altered FPG and diabetes risk were limited or conflicting. The objective of this study was to evaluate the potential associations of heavy metals and essential trace elements with FPG and diabetes risk among general Chinese population. We conducted a cross-sectional study to investigate the associations of urinary concentrations of 23 metals with FPG, impaired fasting glucose (IFG) and diabetes among 2242 community-based Chinese adults in Wuhan. We used the false discovery rate (FDR) method to correct for multiple hypothesis tests. After adjusting for potential confounders, urinary aluminum, titanium, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, antimony, barium, tungsten and lead were associated with altered FPG, IFG or diabetes risk (all P< 0.05); arsenic was only dose-dependently related to diabetes (P< 0.05). After additional adjustment for multiple testing, titanium, copper, zinc, selenium, rubidium, tungsten and lead were still significantly associated with one or more outcomes (all FDR-adjusted P< 0.05). Our results suggest that multiple metals in urine are associated with FPG, IFG or diabetes risk. Because the cross-sectional design precludes inferences about causality, further prospective studies are warranted to validate our findings.

Urinary Arsenic in Human Samples from Areas Characterized by Natural or Anthropogenic Pollution in Italy.

PubMed

Minichilli, Fabrizio; Bianchi, Fabrizio; Ronchi, Anna Maria; Gorini, Francesca; Bustaffa, Elisa

2018-02-09

Arsenic is ubiquitous and has a potentially adverse impact on human health. We compared the distribution of concentrations of urinary inorganic arsenic plus methylated forms (uc(iAs+MMA+DMA)) in four Italian areas with other international studies, and we assessed the relationship between uc(iAs+MMA+DMA) and various exposure factors. We conducted a human biomonitoring study on 271 subjects (132 men) aged 20-44, randomly sampled and stratified by area, gender, and age. Data on environmental and occupational exposure and dietary habits were collected through a questionnaire. Arsenic was speciated using chromatographic separation and inductively coupled mass spectrometry. Associations between uc(iAs+MMA+DMA) and exposure factors were evaluated using the geometric mean ratio (GMR) with a 90% confidence interval by stepwise multiple regression analysis. The 95th percentile value of uc(iAs+MMA+DMA) for the whole sample (86.28 µg/L) was higher than other national studies worldwide. A statistical significant correlation was found between uc(iAs+MMA+DMA) and occupational exposure (GMR: 2.68 [1.79-4.00]), GSTT gene (GMR: 0.68 [0.52-0.80]), consumption of tap water (GMR: 1.35 [1.02-1.77]), seafood (GMR: 1.44 [1.11-1.88]), whole milk (GMR: 1.34 [1.04-1.73]), and fruit/vegetables (GMR: 1.37 [1.03-1.82]). This study demonstrated the utility of uc(iAs+MMA+DMA) as a biomarker to assess environmental exposure. In a public health context, this information could be used to support remedial action, to prevent individuals from being further exposed to environmental arsenic sources.

Urinary Arsenic in Human Samples from Areas Characterized by Natural or Anthropogenic Pollution in Italy

PubMed Central

Minichilli, Fabrizio; Bianchi, Fabrizio; Ronchi, Anna Maria; Gorini, Francesca; Bustaffa, Elisa

2018-01-01

Arsenic is ubiquitous and has a potentially adverse impact on human health. We compared the distribution of concentrations of urinary inorganic arsenic plus methylated forms (uc(iAs+MMA+DMA)) in four Italian areas with other international studies, and we assessed the relationship between uc(iAs+MMA+DMA) and various exposure factors. We conducted a human biomonitoring study on 271 subjects (132 men) aged 20–44, randomly sampled and stratified by area, gender, and age. Data on environmental and occupational exposure and dietary habits were collected through a questionnaire. Arsenic was speciated using chromatographic separation and inductively coupled mass spectrometry. Associations between uc(iAs+MMA+DMA) and exposure factors were evaluated using the geometric mean ratio (GMR) with a 90% confidence interval by stepwise multiple regression analysis. The 95th percentile value of uc(iAs+MMA+DMA) for the whole sample (86.28 µg/L) was higher than other national studies worldwide. A statistical significant correlation was found between uc(iAs+MMA+DMA) and occupational exposure (GMR: 2.68 [1.79–4.00]), GSTT gene (GMR: 0.68 [0.52–0.80]), consumption of tap water (GMR: 1.35 [1.02–1.77]), seafood (GMR: 1.44 [1.11–1.88]), whole milk (GMR: 1.34 [1.04–1.73]), and fruit/vegetables (GMR: 1.37 [1.03–1.82]). This study demonstrated the utility of uc(iAs+MMA+DMA) as a biomarker to assess environmental exposure. In a public health context, this information could be used to support remedial action, to prevent individuals from being further exposed to environmental arsenic sources. PMID:29425136

Changes in Serum Adiponectin in Mice Chronically Exposed to Inorganic Arsenic in Drinking Water.

PubMed

Song, Xuanbo; Li, Ying; Liu, Junqiu; Ji, Xiaohong; Zhao, Lijun; Wei, Yudan

2017-09-01

Cardiovascular disease and diabetes mellitus are prominent features of glucose and lipid metabolism disorders. Adiponectin is a key adipokine that is largely involved in glucose and lipid metabolism processes. A growing body of evidence suggests that chronic exposure to inorganic arsenic is associated with cardiovascular disease and diabetes mellitus. We hypothesized that arsenic exposure may increase the risk of cardiovascular disease and diabetes mellitus by affecting the level of adiponectin. In this study, we examined serum adiponectin levels, as well as serum levels of metabolic measures (including fasting blood glucose, insulin, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol) in C57BL/6 mice exposed to inorganic arsenic in drinking water (5 and 50 ppm NaAsO 2 ) for 18 weeks. Body mass and adiposity were monitored throughout the study. We found no significant changes in serum insulin and glucose levels in mice treated with arsenic for 18 weeks. However, arsenic exposure decreased serum levels of adiponectin, triglyceride, and HDL-cholesterol. Further, an inverse relationship was observed between urinary concentrations of total arsenic and serum levels of adiponectin. This study suggests that arsenic exposure could disturb the metabolism of lipids and increase the risk of cardiovascular disease by reducing the level of adiponectin.

Treating chronic arsenic toxicity with high selenium lentil diets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sah, Shweta; Vandenberg, Albert; Smits, Judit, E-mail: judit.smits@ucalgary.ca

2013-10-01

Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we comparemore » diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell response.« less

GENE EXPRESSION PROFILING OF NORMAL HUMAN BRONCHIAL EPITHELIAL CELLS EXPOSED TO TRIVALENT ARSENICALS AND DIMETHYLTHIOARSINIC ACID

EPA Science Inventory

Lung is a major target for arsenic carcinogenesis in humans. However, the carcinogenic mode of action of arsenicals is unknown. We investigated, in human bronchial epithelial (BEAS2B) cells, the effects of inorganic arsenic (iAsIII), monomethylarsonous acid (MMAIII), dimethylarsi...

PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENIC EXPOSURES

EPA Science Inventory

Chronic exposure to arsenic has been associated with human cancers of the bladder, kidney, lung, liver, and skin. Inorganic arsenic is biotransformed in a stepwise manner via both a reduction and then an oxidative methylation step in which arsenic cycles between +5 and +3 oxidati...

PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENICAL EXPOSURES (SOT 2008)

EPA Science Inventory

Chronic exposure to arsenic has been associated with human cancers of the bladder, kidney, lung, liver, and skin. Inorganic arsenic is biotransformed in a stepwise manner via both a reduction and then an oxidative methylation step in which arsenic cycles between +5 and +3 oxidati...

PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENICAL EXPOSURES

EPA Science Inventory

Chronic exposure to arsenic has been associated with human cancers of the bladder, kidney, lung, liver, and skin. Inorganic arsenic is biotransformed in a stepwise manner via both a reduction and then an oxidative methylation step in which arsenic cycles between +5 and +3 oxidati...

Arsenic metabolism efficiency has a causal role in arsenic toxicity: Mendelian randomization and gene-environment interaction.

PubMed

Pierce, Brandon L; Tong, Lin; Argos, Maria; Gao, Jianjun; Farzana, Jasmine; Roy, Shantanu; Paul-Brutus, Rachelle; Rahaman, Ronald; Rakibuz-Zaman, Muhammad; Parvez, Faruque; Ahmed, Alauddin; Quasem, Iftekhar; Hore, Samar K; Alam, Shafiul; Islam, Tariqul; Harjes, Judith; Sarwar, Golam; Slavkovich, Vesna; Gamble, Mary V; Chen, Yu; Yunus, Mohammad; Rahman, Mahfuzar; Baron, John A; Graziano, Joseph H; Ahsan, Habibul

2013-12-01

Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal. Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid(MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls. Causal odds ratios for skin lesions were 0.90 (95% confidence interval[CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36)for a one standard deviation increase in DMA%, MMA% and iAs%,respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62). We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions.exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.

Impaired arsenic metabolism in children during weaning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faengstroem, Britta; Hamadani, Jena; Nermell, Barbro

2009-09-01

Background: Methylation of inorganic arsenic (iAs) via one-carbon metabolism is a susceptibility factor for a range of arsenic-related health effects, but there is no data on the importance of arsenic metabolism for effects on child development. Aim: To elucidate the development of arsenic metabolism in early childhood. Methods: We measured iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA), the metabolites of iAs, in spot urine samples of 2400 children at 18 months of age. The children were born to women participating in a population-based longitudinal study of arsenic effects on pregnancy outcomes and child development, carried out in Matlab, amore » rural area in Bangladesh with a wide range of arsenic concentrations in drinking water. Arsenic metabolism was evaluated in relation to age, sex, anthropometry, socio-economic status and arsenic exposure. Results: Arsenic concentrations in child urine (median 34 {mu}g/L, range 2.4-940 {mu}g/L), adjusted to average specific gravity of 1.009 g/mL, were considerably higher than that measured at 3 months of age, but lower than that in maternal urine. Child urine contained on average 12% iAs, 9.4% MA and 78% DMA, which implies a marked change in metabolite pattern since infancy. In particular, there was a marked increase in urinary %MA, which has been associated with increased risk of health effects. Conclusion: The arsenic metabolite pattern in urine of children at 18 months of age in rural Bangladesh indicates a marked decrease in arsenic methylation efficiency during weaning.« less

Urinary excretion of platinum, arsenic and selenium of cancer patients from the Antofagasta region in Chile treated with platinum-based drugs

PubMed Central

2012-01-01

Background Arsenic exposure increases the risk of non-cancerous and cancerous diseases. In the Antofagasta region in Chile, an established relationship exists between arsenic exposure and the risk of cancer of the bladder, lung and skin. Platinum-based drugs are first-line treatments, and many works recognise selenium as a cancer-fighting nutrient. We characterised the short-term urinary excretion amounts of arsenic, selenium and platinum in 24-h urine samples from patients with lung cancer and those with cancer other than lung treated with cisplatin or/and carboplatin. As - Se - Pt inter-element relationships were also investigated. Results The amounts of platinum excreted in urine were not significantly different between patients with lung cancer and those with other cancers treated with cisplatin, despite the significant variation in platinum amounts supplied from platinum-based drugs. In general, the analytical amounts of excreted selenium were greater than those for arsenic, which could imply that platinum favours the excretion of selenium. For other types of cancers treated with drugs without platinum, excretion of selenium was also greater than that of arsenic, suggesting an antagonist selenium-anti-cancer drug relationship. Conclusions Regards the baseline status of patients, the analytical amounts of excreted Se is greater than those for As, particularly, for cisplatin chemotherapy. This finding could imply that for over the As displacement Pt favours the excretion of Se. The analytical amounts of excreted Se were greater than those for As, either with and without Pt-containing drugs, suggesting an antagonist Se-anti-cancer drug relationship. However, it seemed that differences existed between As - Se - Pt inter-element associations in patients treated for lung cancer in comparison with those treated for cancer other than lung. Therefore, knowledge obtained in this work, can contribute to understanding the arsenic cancer mechanism and the As - Se - Pt inter-element association for lung cancer and other types of cancer, which in some cases respond at a linear mathematical model. PMID:22546077

Containing arsenic-enriched groundwater tracing lead isotopic compositions of common arsenical pesticides in a coastal Maine watershed

USGS Publications Warehouse

Ayuso, Robert A.; Foley, Nora K.; Robinson, Glipin R.; Colvin, A.S.; Lipfert, G.; Reeve, A.S.

2006-01-01

Arsenical pesticides and herbicides were extensively used on apple, blueberry, and potato crops in New England during the first half of the twentieth century. Lead arsenate was the most heavily used arsenical pesticide until it was officially banned. Lead arsenate, calcium arsenate, and sodium arsenate have similar Pb isotope compositions: 208Pb207Pb = 2.3839-2.4722, and 206Pb207Pb = 1.1035-1.2010. Other arsenical pesticides such as copper acetoarsenite (Paris green), methyl arsonic acid and methane arsonic acid, as well as arsanilic acid are widely variable in isotope composition. Although a complete understanding of the effects of historical use of arsenical pesticides is not available, initial studies indicate that arsenic and lead concentrations in stream sediments in New England are higher in agricultural areas that intensely used arsenical pesticides than in other areas. The Pb isotope compositions of pesticides partially overlap values of stream sediments from areas with the most extensive agricultural use. The lingering effects of arsenical pesticide use were tested in a detailed geochemical and isotopic study of soil profiles from a watershed containing arsenic-enriched ground water in coastal Maine. Acid-leach compositions of the soils represent lead adsorbed to mineral surfaces or held in soluble minerals (Fe- and Mn-hydroxides, carbonate, and some micaceous minerals), whereas residue compositions likely reflect bedrock compositions. The soil profiles contain labile Pb (acid-leach) showing a moderate range in 206Pb 207Pb (1.1870-1.2069), and 208Pb207Pb (2.4519-2.4876). Isotope values vary as a function of depth: the lowest Pb isotope ratios (e.g.,208Pb206Pb) representing labile lead are in the uppermost soil horizons. Lead contents decrease with depth in the soil profiles. Arsenic contents show no clear trend with depth. A multi-component mixing scheme that included lead from the local parent rock (Penobscot Formation), lead derived from combustion of fossil fuels, and possibly lead from other anthropogenic sources (e.g., pesticides), could account for Pb isotope variations in the soil profiles. In agricultural regions, our preliminary data show that the extensive use of arsenical pesticides and herbicides can be a significant anthropogenic source of arsenic and lead to stream sediments and soils.

Metals exposure and risk of small-for-gestational age birth in a Canadian birth cohort: The MIREC study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, Shari; Arbuckle, Tye E., E-mail: Tye.Arbuckle@hc-sc.gc.ca; Fisher, Mandy

Background: Lead, mercury, cadmium and arsenic are some of the most common toxic metals to which Canadians are exposed. The effect of exposure to current low levels of toxic metals on fetal growth restriction is unknown. Objective: The aim of this study was to examine relationships between exposure to lead, mercury, cadmium and arsenic during pregnancy, and risk of small for gestational age (SGA) birth. Methods: Lead, mercury, cadmium and arsenic levels were measured in blood samples from the first and third trimesters in 1835 pregnant women from across Canada. Arsenic species in first trimester urine were also assessed. Relativemore » risks and 95% confidence intervals were estimated using log binomial multivariate regression. Important covariates including maternal age, parity, pre-pregnancy BMI, and smoking, were considered in the analysis. An exploratory analysis was performed to examine potential effect modification of these relationships by single nucleotide polymorphisms (SNPs) in GSTP1 and GSTO1 genes. Results: No association was found between blood lead, cadmium or arsenic and risk for SGA. We observed an increased risk for SGA for the highest compared to the lowest tertile of exposure for mercury (>1.6 µg/L, RR=1.56.; 95% CI=1.04–2.58) and arsenobetaine (>2.25 µg/L, RR=1.65; 95% CI=1.10–2.47) after adjustment for the effects of parity and smoking. A statistically significant interaction was observed in the relationship between dimethylarsinic acid (DMA) levels in urinary arsenic and SGA between strata of GSTO1 A104A (p for interaction=0.02). A marginally significant interaction was observed in the relationship between blood lead and SGA between strata of GSTP1 A114V (p for interaction=0.06). Conclusions: These results suggest a small increase in risk for SGA in infants born to women exposed to mercury and arsenic. Given the conflicting evidence in the literature this warrants further investigation in other pregnant populations. - Highlights: • Metals measured in blood or urine of pregnant women. • No association between blood lead, cadmium or arsenic and SGA. • Small increased risk for highest tertile of blood mercury. • Small increased risk for highest tertile of urinary arsenobetaine. • Further research needed to confirm observed associations.« less

The effect of association between inefficient arsenic methylation capacity and demographic characteristics on the risk of skin lesions.

PubMed

Rasheed, Hifza; Kay, Paul; Slack, Rebecca; Gong, Yun Yun

2018-01-15

This study was conducted in rural Pakistan to assess the dose-response relationship between skin lesions and arsenic exposure and their variation by demographic characteristics. The study included 398 participants (66 participants with skin lesions and 332 without) residing in six previously unstudied villages exposed to ground water arsenic in the range of <1 to 3090μgL -1 . The skin lesions identification process involved interview and physical examinations of participants followed by confirmation by a physician according to UNICEF criteria. Urinary inorganic arsenic (iAs), total arsenic (tAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analysed to determine methylation capacity, methylation efficiency and the dose-response relationship with skin lesions. Study participants with skin lesions were found to be exposed to arsenic >10μgL -1 with a daily arsenic intake of 3.23±3.75mgday -1 from household ground water sources for an exposure duration of 10-20years. The participants with skin lesions compared to those without skin lesions showed higher levels of urinary iAs (133.40±242.48 vs. 44.24±86.48μgg -1 Cr), MMA (106.38±135.04 vs. 35.43±39.97μgg -1 Cr), MMA% (15.26±6.31 vs.12.11±4.68) and lower levels of DMA% (66.99±13.59 vs. 73.39±10.44) and secondary methylation index (SMI) (0.81±0.11 vs. 0.86±0.07). Study participants carrying a lower methylation capacity characterized by higher MMA% (OR 5.06, 95% CI: 2.09-12.27), lower DMA% (OR 0.64, 95% CI: 0.33-1.26), primary methylation index (PMI) (OR 0.56, 95% CI: 0.28-1.12) and SMI (OR 0.43, 95% CI: 0.21-0.88) had a significantly higher risk of skin lesions compared to their corresponding references after adjusting for occupation categories. The findings confirmed that inefficient arsenic methylation capacity was significantly associated with increased skin lesion risks and the effect might be modified by labour intensive occupations. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Human exposure to arsenic from drinking water in Vietnam.

PubMed

Agusa, Tetsuro; Trang, Pham Thi Kim; Lan, Vi Mai; Anh, Duong Hong; Tanabe, Shinsuke; Viet, Pham Hung; Berg, Michael

2014-08-01

Vietnam is an agricultural country with a population of about 88 million, with some 18 million inhabitants living in the Red River Delta in Northern Vietnam. The present study reports the chemical analyses of 68 water and 213 biological (human hair and urine) samples conducted to investigate arsenic contamination in tube well water and human arsenic exposure in four districts (Tu Liem, Dan Phuong, Ly Nhan, and Hoai Duc) in the Red River Delta. Arsenic concentrations in groundwater in these areas were in the range of <1 to 632 μg/L, with severe contamination found in the communities Ly Nhan, Hoai Duc, and Dan Phuong. Arsenic concentrations were markedly lowered in water treated with sand filters, except for groundwater from Hoai Duc. Human hair samples had arsenic levels in the range of 0.07-7.51 μg/g, and among residents exposed to arsenic levels ≥50 μg/L, 64% of them had hair arsenic concentrations higher than 1 μg/g, which is a level that can cause skin lesions. Urinary arsenic concentrations were 4-435 μg/g creatinine. Concentrations of arsenic in hair and urine increased significantly with increasing arsenic content in drinking water, indicating that drinking water is a significant source of arsenic exposure for these residents. The percentage of inorganic arsenic (IA) in urine decreased with age, whereas the opposite trend was observed for monomethylarsonic acid (MMA) in urine. Significant co-interactions of age and arsenic exposure status were also detected for concentrations of arsenic in hair and the sum of IA, MMA, and dimethylarsinic acid (DMA) in urine and %MMA. In summary, this study demonstrates that a considerable proportion of the Vietnamese population is exposed to arsenic levels of chronic toxicity, even if sand filters reduce exposure in many households. Health problems caused by arsenic ingestion through drinking water are increasingly reported in Vietnam. © 2013 Elsevier B.V. All rights reserved.

Lead isotopic compositions of soil and near-surface till profiles from a watershed containing arsenic-enriched groundwater in coastal Maine

USGS Publications Warehouse

Ayuso, Robert; Foley, Nora; Wandless, Gregory; Dillingham, Jeremy; Colvin, Anna

2005-01-01

Lead isotope compositions of soils and near-surface tills from an area of coastal Maine known to have groundwater with anomalously high arsenic contents were measured in order to determine the source of the lead and, by inference, possible sources of arsenic. Five soil and till sites were selected for detailed chemical and isotopic analysis. To construct profiles of the soil and till horizons, five samples were collected at 10-cm intervals from the surface to the base of each horizon. Total lead and arsenic concentrations and lead isotopic compositions were measured for 48 leaches and bulk residues. The soils and tills are underlain by sulfidic schists of the Penobscot Formation. Several generations of minerals containing arsenic and lead exist in the regional bedrock, including rock-forming silicates (feldspar and micas), sulfide minerals formed during diagenesis (for example, arsenic-rich pyrite), and sulfide and oxide minerals that formed as a result of Silurian metamorphic and igneous events (for example, arsenopyrite, galena, iron-oxides, and arsenic-sulfides). A young group of secondary minerals (for example, iron-hydroxides, arsenic-hydroxides, lead-sulfate, and arsenic-jarosite) formed from recent weathering and pedogenic processes.

Seasonal perspective of dietary arsenic consumption and urine arsenic in an endemic population.

PubMed

Biswas, Anirban; Deb, Debasree; Ghose, Aloke; Santra, Subhas Chandra; Guha Mazumder, Debendra Nath

2014-07-01

Exposure to arsenic in arsenic endemic areas is most remarkable environmental health challenges. Although effects of arsenic contamination are well established, reports are unavailable on probable seasonal variation due to changes of food habit depending on winter and summer seasons, especially for endemic regions of Nadia district, West Bengal. Complete 24-h diets, drinking-cooking water, first morning voided urine samples, and diet history were analyzed on 25 volunteers in arsenic endemic Chakdah block of Nadia district, once in summer followed by once in winter from the same participants. Results depicted no seasonal variation of body weight and body mass index. Arsenic concentration of source drinking and cooking water decreased (p = 0.04) from 26 μg L(-1) in summer to 6 μg L(-1) in winter season. We recorded a seasonal decrease of water intake in male (3.8 and 2.5 L day (-1)) and female (2.6 and 1.2 L day(-1)) participants from summer to winter. Arsenic intake through drinking water decreased (p = 0.04) in winter (29 μg day(-1)) than in summer (100 μg day(-1)), and urinary arsenic concentration decreased (p = 0.018) in winter (41 μg L(-1)) than in summer (69 μg L(-1)). Dietary arsenic intake remained unchanged (p = 0.24) over the seasons. Hence, we can infer that human health risk assessment from arsenic needs an insight over temporal scale.

Multiple metals exposure in a small-scale artisanal gold mining community.

PubMed

Basu, Niladri; Nam, Dong-Ha; Kwansaa-Ansah, Edward; Renne, Elisha P; Nriagu, Jerome O

2011-04-01

Urinary metals were characterized in 57 male residents of a small-scale gold mining community in Ghana. Chromium and arsenic exceeded health guideline values for 52% and 34%, respectively, of all participants. About 10-40% of the participants had urinary levels of aluminum, copper, manganese, nickel, selenium, and zinc that fell outside the U.S. reference range. Exposures appear ubiquitous across the community as none of the elements were associated with occupation, age, and diet. Copyright © 2011 Elsevier Inc. All rights reserved.

Strain differences in arsenic-induced oxidative lesion via arsenic biomethylation between C57BL/6J and 129X1/SvJ mice

NASA Astrophysics Data System (ADS)

Wu, Ruirui; Wu, Xiafang; Wang, Huihui; Fang, Xin; Li, Yongfang; Gao, Lanyue; Sun, Guifan; Pi, Jingbo; Xu, Yuanyuan

2017-03-01

Arsenic is a common environmental and occupational toxicant with dramatic species differences in its susceptibility and metabolism. Mouse strain variability may provide a better understanding of the arsenic pathological profile but is largely unknown. Here we investigated oxidative lesion induced by acute arsenic exposure in the two frequently used mouse strains C57BL/6J and 129X1/SvJ in classical gene targeting technique. A dose of 5 mg/kg body weight arsenic led to a significant alteration of blood glutathione towards oxidized redox potential and increased hepatic malondialdehyde content in C57BL/6J mice, but not in 129X1/SvJ mice. Hepatic antioxidant enzymes were induced by arsenic in transcription in both strains and many were higher in C57BL/6J than 129X1/SvJ mice. Arsenic profiles in the liver, blood and urine and transcription of genes encoding enzymes involved in arsenic biomethylation all indicate a higher arsenic methylation capacity, which contributes to a faster hepatic arsenic excretion, in 129X1/SvJ mice than C57BL/6J mice. Taken together, C57BL/6J mice are more susceptible to oxidative hepatic injury compared with 129X1/SvJ mice after acute arsenic exposure, which is closely associated with arsenic methylation pattern of the two strains.

Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, Xuefeng, E-mail: xuefengr@buffalo.edu; Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214; Gaile, Daniel P.

Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenicmore » exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is independent to Nfe2l2-signaling pathway. • Expression of several miRNAs predicted to target GCL changed after arsenic exposure.« less

Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima-media thickness in Bangladesh

PubMed Central

Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G.; Liu, Mengling; Cheng, Xin; Parvez, Faruque; Paul-Brutus, Rachelle; Islam, Tariqul; Paul, Rina Rani; Sarwar, Golam; Ahmed, Alauddin; Jiang, Jieying; Islam, Tariqul; Slavkovich, Vesna; Rundek, Tatjana; Demmer, Ryan T.; Desvarieux, Moise; Ahsan, Habibul; Chen, Yu

2014-01-01

Epidemiologic studies that evaluated genetic susceptibility to the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1,078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-medial thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = -5.1 μm, 95% CI = -31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = -3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings. PMID:24593923

Serum levels of the extracellular domain of the epidermal growth factor receptor in individuals exposed to arsenic in drinking water in Bangladesh.

PubMed

Li, Y; Chen, Y; Slavkovic, V; Ahsan, H; Parvez, F; Graziano, J H; Brandt-Rauf, P W

2007-01-01

Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (p

Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima-media thickness in Bangladesh.

PubMed

Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G; Liu, Mengling; Cheng, Xin; Parvez, Faruque; Paul-Brutus, Rachelle; Paul, Rina Rani; Sarwar, Golam; Ahmed, Alauddin; Jiang, Jieying; Islam, Tariqul; Slavkovich, Vesna; Rundek, Tatjana; Demmer, Ryan T; Desvarieux, Moise; Ahsan, Habibul; Chen, Yu

2014-05-01

Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = -5.1 μm, 95% CI = -31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = -3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings. Copyright © 2014 Elsevier Inc. All rights reserved.

High-Resolution Computed Tomography and Pulmonary Function Findings of Occupational Arsenic Exposure in Workers.

PubMed

Ergün, Recai; Evcik, Ender; Ergün, Dilek; Ergan, Begüm; Özkan, Esin; Gündüz, Özge

2017-05-05

The number of studies where non-malignant pulmonary diseases are evaluated after occupational arsenic exposure is very few. To investigate the effects of occupational arsenic exposure on the lung by high-resolution computed tomography and pulmonary function tests. Retrospective cross-sectional study. In this study, 256 workers with suspected respiratory occupational arsenic exposure were included, with an average age of 32.9±7.8 years and an average of 3.5±2.7 working years. Hair and urinary arsenic levels were analysed. High-resolution computed tomography and pulmonary function tests were done. In workers with occupational arsenic exposure, high-resolution computed tomography showed 18.8% pulmonary involvement. In pulmonary involvement, pulmonary nodule was the most frequently seen lesion (64.5%). The other findings of pulmonary involvement were 18.8% diffuse interstitial lung disease, 12.5% bronchiectasis, and 27.1% bullae-emphysema. The mean age of patients with pulmonary involvement was higher and as they smoked more. The pulmonary involvement was 5.2 times higher in patients with skin lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was significantly lower in patients with pulmonary involvement. Besides lung cancer, chronic occupational inhalation of arsenic exposure may cause non-malignant pulmonary findings such as bronchiectasis, pulmonary nodules and diffuse interstitial lung disease. So, in order to detect pulmonary involvement in the early stages, workers who experience occupational arsenic exposure should be followed by diffusion test and high-resolution computed tomography.

[Exploration of Epigenetic Changes and DNA Methylation Markers Associated with Liver Tumors Induced by Inorganic Arsenite Exposure in Mice].

PubMed

Suzuki, Takehiro; Nohara, Keiko

2015-01-01

Naturally occurring inorganic arsenic is known to increase the risk of cancers of the skin and several other organs, including the urinary bladder, lung, and liver. Epidemiological studies have also indicated that gestational arsenic exposure is associated with increased incidences of cancers in several organs, including the bladder and liver, in adulthood. Previous studies have shown that epigenetic changes are involved in arsenic-induced carcinogenesis. Among epigenetic changes, DNA methylation changes that are specific to arsenic-induced tumors would be useful for distinguishing such tumors from tumors induced by other factors and for clarifying arsenic carcinogenesis. It has been reported that gestational arsenic exposure of C3H mice, whose males tend to spontaneously develop liver tumors, increases the incidence of tumors in the male offspring. Using the same experimental protocol, we found a number of regions where the DNA methylation status was altered in the liver tumors compared with the normal liver tissues by the methylated DNA immunoprecipitation (MeDIP)-CpG island microarray method. Among such regions, we demonstrated using real-time methylation-specific PCR and bisulfite sequencing that a gene body region of the oncogene Fosb underwent alteration in DNA methylation following gestational arsenic exposure. We also showed that the Fosb expression level significantly increased following gestational arsenic exposure. These findings suggest that the DNA methylation status of the Fosb region is implicated in tumor augmentation and can also be utilized for characterizing tumors induced by gestational arsenic exposure.

Polymorphic trial in oxidative damage of arsenic exposed Vietnamese.

PubMed

Fujihara, Junko; Soejima, Mikiko; Yasuda, Toshihiro; Koda, Yoshiro; Kunito, Takashi; Iwata, Hisato; Tanabe, Shinsuke; Takeshita, Haruo

2011-10-15

Arsenic causes DNA damage and changes the cellular capacity for DNA repair. Genes in the base excision repair (BER) pathway influence the generation and repair of oxidative lesions. Single nucleotide polymorphisms (SNPs) in human 8-oxoguanine DNA glycosylase (hOGG1) Ser326Cys; apurinic/apyrimidinic endonuclease (APE1) Asp148Glu; X-ray and repair and cross-complementing group 1 (XRCC1) Arg280His and Arg399Gln in the BER genes were analyzed, and the relationship between these 4 SNPs and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations of 100 Vietnamese population exposed to arsenic was investigated. Individuals with hOGG1 326Cys/Cys showed significantly higher urinary 8-OHdG concentrations than did those with 326 Ser/Cys and Ser/Ser. As for APE1 Asp148Glu, heterozygous subjects showed significantly higher urinary 8-OHdG concentrations than did those homozygous for Asp/Asp. Moreover, global ethnic comparison of the allelic frequencies of the 4SNPs was performed in 10 population and previous reported data. The mutant allele frequencies of hOGG1 Ser326Cys in the Asian populations were higher than those in the African and Caucasian populations. As for APE1 Asp148Glu, Caucasians showed higher mutant frequencies than those shown by African and Asian populations. Among Asian populations, the Bangladeshi population showed relatively higher mutant allele frequencies of the APE1 Asp148Glu polymorphism. This study is the first to demonstrate the existence of genetic heterogeneity in a worldwide distribution of SNPs (hOGG1 Ser326Cys, APE1 Asp148Glu, XRCC1 Arg280His, and XRCC1 Arg399Gln) in the BER genes. Published by Elsevier Inc.

Interaction of plasma glutathione redox and folate deficiency on arsenic methylation capacity in Bangladeshi adults

PubMed Central

Niedzwiecki, Megan M.; Hall, Megan N.; Liu, Xinhua; Slavkovich, Vesna; Ilievski, Vesna; Levy, Diane; Alam, Shafiul; Siddique, Abu B.; Parvez, Faruque; Graziano, Joseph H.; Gamble, Mary V.

2014-01-01

Inorganic arsenic (InAs) is metabolized through a series of methylation reactions catalyzed by arsenic(III)-methyltransferase (AS3MT), resulting in the generation of monomethylarsonic (MMAs) and dimethylarsinic acids (DMAs). AS3MT activity requires the presence of the methyl donor S-adenosylmethionine (SAM), a product of folate-dependent one-carbon metabolism, and a reductant. Although glutathione (GSH), the primary endogenous antioxidant, is not required for As methylation, GSH stimulates As methylation rates in vitro. However, the relationship between GSH redox and As methylation capacity in humans is unknown. We wished to test the hypothesis that a more oxidized plasma GSH redox status is associated with decreased As methylation capacity, and examine whether these associations are modified by folate nutritional status. Concentrations of plasma GSH and GSSG, plasma folate, total blood As (bAs), total urinary As (uAs), and uAs metabolites were assessed in a cross-sectional study of n = 376 Bangladeshi adults who were chronically exposed to As in drinking water. We observed that a decreased plasma GSH/GSSG ratio (reflecting a more oxidized redox state) was significantly associated with increased urinary %MMA, decreased urinary %DMA, and increased total bAs in folate-deficient individuals (plasma folate ≤ 9.0 nmol/L). Concentrations of plasma GSH and GSSG were independently associated with increased and decreased As methylation capacity, respectively. No significant associations were observed in folate-sufficient individuals, and interactions by folate status were statistically significant. Our findings suggest that GSH/GSSG redox regulation might contribute to the large interindividual variation in As methylation capacity observed in human populations. PMID:24726863

GENE EXPRESSION PROFILES IN ARSENIC-TREATED MCF-7 BREAST CANCER CELLS EXPRESSING DIFFERENT LEVELS OF HSP70

EPA Science Inventory

Gene expression profiles in arsenic-treated MCF-7 breast cancer cells expressing different levels of HSP70

Gail Nelson, Susan Hester, Ernest Winkfield, Jill Barnes, James Allen
Environmental Carcinogenesis Division, NHEERL, ORD, US Environmental Protection Agency, Rese...

DNA methylation of extracellular matrix remodeling genes in children exposed to arsenic.

PubMed

Gonzalez-Cortes, Tania; Recio-Vega, Rogelio; Lantz, Robert Clark; Chau, Binh T

2017-08-15

Several novel mechanistic findings regarding to arsenic's pathogenesis has been reported and some of them suggest that the etiology of some arsenic induced diseases are due in part to heritable changes to the genome via epigenetic processes such as DNA methylation, histone maintenance, and mRNA expression. Recently, we reported that arsenic exposure during in utero and early life was associated with impairment in the lung function and abnormal receptor for advanced glycation endproducts (RAGE), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) sputum levels. Based on our results and the reported arsenic impacts on DNA methylation, we designed this study in our cohort of children exposed in utero and early childhood to arsenic with the aim to associate DNA methylation of MMP9, TIMP1 and RAGE genes with its protein sputum levels and with urinary and toenail arsenic levels. The results disclosed hypermethylation in MMP9 promotor region in the most exposed children; and an increase in the RAGE sputum levels among children with the mid methylation level; there were also positive associations between MMP9 DNA methylation with arsenic toenail concentrations; RAGE DNA methylation with iAs, and %DMA; and finally between TIMP1 DNA methylation with the first arsenic methylation. A negative correlation between MMP9 sputum levels with its DNA methylation was registered. In conclusion, arsenic levels were positive associated with the DNA methylation of extracellular matrix remodeling genes;, which in turn could modifies the biological process in which they are involved causing or predisposing to lung diseases. Copyright © 2017. Published by Elsevier Inc.

Availability of arsenic in human milk in women and its correlation with arsenic in urine of breastfed children living in arsenic contaminated areas in Bangladesh.

PubMed

Islam, Md Rafiqul; Attia, John; Alauddin, Mohammad; McEvoy, Mark; McElduff, Patrick; Slater, Christine; Islam, Md Monirul; Akhter, Ayesha; d'Este, Catherine; Peel, Roseanne; Akter, Shahnaz; Smith, Wayne; Begg, Stephen; Milton, Abul Hasnat

2014-12-04

Early life exposure to inorganic arsenic may be related to adverse health effects in later life. However, there are few data on postnatal arsenic exposure via human milk. In this study, we aimed to determine arsenic levels in human milk and the correlation between arsenic in human milk and arsenic in mothers and infants urine. Between March 2011 and March 2012, this prospective study identified a total of 120 new mother-baby pairs from Kashiani (subdistrict), Bangladesh. Of these, 30 mothers were randomly selected for human milk samples at 1, 6 and 9 months post-natally; the same mother baby pairs were selected for urine sampling at 1 and 6 months. Twelve urine samples from these 30 mother baby pairs were randomly selected for arsenic speciation. Arsenic concentration in human milk was low and non-normally distributed. The median arsenic concentration in human milk at all three time points remained at 0.5 μg/L. In the mixed model estimates, arsenic concentration in human milk was non-significantly reduced by -0.035 μg/L (95% CI: -0.09 to 0.02) between 1 and 6 months and between 6 and 9 months. With the progression of time, arsenic concentration in infant's urine increased non-significantly by 0.13 μg/L (95% CI: -1.27 to 1.53). Arsenic in human milk at 1 and 6 months was not correlated with arsenic in the infant's urine at the same time points (r = -0.13 at 1 month and r = -0.09 at 6 month). Arsenite (AsIII), arsenate (AsV), monomethyl arsonic acid (MMA), dimethyl arsinic acid (DMA) and arsenobetaine (AsB) were the constituents of total urinary arsenic; DMA was the predominant arsenic metabolite in infant urine. We observed a low arsenic concentration in human milk. The concentration was lower than the World Health Organization's maximum permissible limit (WHO Permissible Limit 15 μg/kg-bw/week). Our findings support the safety of breastfeeding even in arsenic contaminated areas.

Urinary inorganic arsenic concentrations and semen quality of male partners of subfertile couples in Tokyo.

PubMed

Oguri, Tomoko; Yoshinaga, Jun; Toshima, Hiroki; Mizumoto, Yoshifumi; Hatakeyama, Shota; Tokuoka, Susumu

2016-01-01

Inorganic arsenic (iAs) has been known as a testicular toxicant in experimental rodents. Possible association between iAs exposure and semen quality (semen volume, sperm concentration, and sperm motility) was explored in male partners of couples (n = 42) who visited a gynecology clinic in Tokyo for infertility consultation. Semen parameters were measured according to WHO guideline at the clinic, and urinary iAs and methylarsonic acid (MMA), and dimethylarsinic acid concentrations were determined by liquid chromatography-hydride generation-ICP mass spectrometry. Biological attributes, dietary habits, and exposure levels to other chemicals with known effects on semen parameters were taken into consideration as covariates. Multiple regression analyses and logistic regression analyses did not find iAs exposure as significant contributor to semen parameters. Lower exposure level of subjects (estimated to be 0.5 μg kg(-1) day(-1)) was considered a reason of the absence of adverse effects on semen parameters, which were seen in rodents dosed with 4-7.5 mg kg(-1).

Population-Based Case–Control Study of Chinese Herbal Products Containing Aristolochic Acid and Urinary Tract Cancer Risk

PubMed Central

Lai, Ming-Nan; Chen, Pau-Chung; Chen, Ya-Yin

2010-01-01

Background Consumption of Chinese herbs that contain aristolochic acid (eg, Mu Tong) has been associated with an increased risk of urinary tract cancer. Methods We conducted a population-based case–control study in Taiwan to examine the association between prescribed Chinese herbal products that contain aristolochic acid and urinary tract cancer. All patients newly diagnosed with urinary tract cancer (case subjects) from January 1, 2001, to December 31, 2002, and a random sample of the entire insured population from January 1, 1997, to December 31, 2002 (control subjects), were selected from the National Health Insurance reimbursement database. Subjects who were ever prescribed more than 500 pills of nonsteroidal anti-inflammatory drugs and/or acetaminophen were excluded, leaving 4594 case patients and 174 701 control subjects in the final analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multivariable logistic regression models for the association between prescribed Chinese herbs containing aristolochic acid and the occurrence of urinary tract cancer. Models were adjusted for age, sex, residence in a township where black foot disease was endemic (an indicator of chronic arsenic exposure from drinking water [a risk factor for urinary tract cancer]), and history of chronic urinary tract infection. Statistical tests were two-sided. Results Having been prescribed more than 60 g of Mu Tong and an estimated consumption of more than 150 mg of aristolochic acid were independently associated with an increased risk for urinary tract cancer in multivariable analyses (Mu Tong: at 61–100 g, OR = 1.6, 95% CI = 1.3 to 2.1, and at >200 g, OR = 2.1, 95% CI = 1.3 to 3.4; aristolochic acid: at 151–250 mg, OR = 1.4, 95% CI = 1.1 to 1.8, and at >500 mg, OR = 2.0, 95% CI = 1.4 to 2.9). A statistically significant linear dose–response relationship was observed between the prescribed dose of Mu Tong or the estimated cumulative dose of aristolochic acid and the risk of urinary tract cancer (P < .001 for both). Conclusions Consumption of aristolochic acid–containing Chinese herbal products is associated with an increased risk of cancer of the urinary tract in a dose-dependent manner that is independent of arsenic exposure. PMID:20026811

Polymorphisms in Arsenic(+III Oxidation State) Methyltransferase (AS3MT) Predict Gene Expression of AS3MT as Well as Arsenic Metabolism

PubMed Central

Engström, Karin; Vahter, Marie; Mlakar, Simona Jurkovic; Concha, Gabriela; Nermell, Barbro; Raqib, Rubhana; Cardozo, Alejandro; Broberg, Karin

2011-01-01

Background Arsenic (As) occurs as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in humans, and the methylation pattern demonstrates large interindividual differences. The fraction of urinary MMA is a marker for susceptibility to As-related diseases. Objectives We evaluated the impact of polymorphisms in five methyltransferase genes on As metabolism in two populations, one in South America and one in Southeast Asia. The methyltransferase genes were arsenic(+III oxidation state) methyltransferase (AS3MT), DNA-methyltransferase 1a and 3b (DNMT1a and DNMT3b, respectively), phosphatidylethanolamine N-methyltransferase (PEMT), and betaine-homocysteine methyltransferase (BHMT). AS3MT expression was analyzed in peripheral blood. Methods Subjects were women exposed to As in drinking water in the Argentinean Andes [n = 172; median total urinary As (U-As), 200 μg/L] and in rural Bangladesh (n = 361; U-As, 100 μg/L; all in early pregnancy). Urinary As metabolites were measured by high-pressure liquid chromatography/inductively coupled plasma mass spectrometry. Polymorphisms (n = 22) were genotyped with Sequenom, and AS3MT expression was measured by quantitative real-time polymerase chain reaction using TaqMan expression assays. Results Six AS3MT polymorphisms were significantly associated with As metabolite patterns in both populations (p ≤ 0.01). The most frequent AS3MT haplotype in Bangladesh was associated with a higher percentage of MMA (%MMA), and the most frequent haplotype in Argentina was associated with a lower %MMA and a higher percentage of DMA. Four polymorphisms in the DNMT genes were associated with metabolite patterns in Bangladesh. Noncoding AS3MT polymorphisms affected gene expression of AS3MT in peripheral blood, demonstrating that one functional impact of AS3MT polymorphisms may be altered levels of gene expression. Conclusions Polymorphisms in AS3MT significantly predicted As metabolism across these two very different populations, suggesting that AS3MT may have an impact on As metabolite patterns in populations worldwide. PMID:21247820

Arsenic levels in ground water and cancer incidence in Idaho: an ecologic study.

PubMed

Han, Yueh-Ying; Weissfeld, Joel L; Davis, Devra L; Talbott, Evelyn O

2009-07-01

Long-term exposure to arsenic above 50 microg/L in drinking water has been related to multiple types of cancers. Few epidemiologic studies conducted in the US have detected an association between regional exposures below this level in drinking water and corresponding cancer occurrence rates. This county-level ecologic study evaluates arsenic levels in ground water and its association with targeted cancer incidence in Idaho, where some regions have been found to contain higher arsenic levels. Using cancer incidence data (1991-2005) from the Cancer Data Registry of Idaho and arsenic data (1991-2005) from the Idaho Department of Environmental Quality, we calculated the age-adjusted incidence rate for cancers of the urinary bladder, kidney and renal pelvis, liver and bile duct, lung and bronchus, non-Hodgkin's lymphoma (NHL), and all malignant cancers according to arsenic levels in ground water. Multivariate regression analysis was applied to evaluate the relationship between arsenic levels in ground water and cancer incidence. For males, but not for females, age-adjusted incidence for lung cancer and all malignant cancers was significantly higher in the intermediate arsenic counties (2-9 microg/L, n = 16) and the high arsenic counties (>or=10 microg/L, n = 5) compared to the low arsenic counties (<2.0 microg/L, n = 23). When adjusted for race, gender, population density, smoking and body mass index (BMI), no relationship was found between arsenic levels in ground water and cancer incidence. In this ecological design, exposure to low-level arsenic in ground water is not associated with cancer incidence when adjusting for salient variables. For populations residing in southwestern Idaho, where arsenic has been found to exceed 10 microg/L in ground water, individual risk assessment is required in order to determine whether there is a link between long-term arsenic exposure at these levels and cancer risk.

Poultry Consumption and Arsenic Exposure in the U.S. Population

PubMed Central

Nigra, Anne E.; Nachman, Keeve E.; Love, David C.; Grau-Perez, Maria; Navas-Acien, Ana

2016-01-01

Background: Arsenicals (roxarsone and nitarsone) used in poultry production likely increase inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and roxarsone or nitarsone concentrations in poultry meat. However, the association between poultry intake and exposure to these arsenic species, as reflected in elevated urinary arsenic concentrations, is unknown. Objectives: Our aim was to evaluate the association between 24-hr dietary recall of poultry consumption and arsenic exposure in the U.S. population. We hypothesized first, that poultry intake would be associated with higher urine arsenic concentrations and second, that the association between turkey intake and increased urine arsenic concentrations would be modified by season, reflecting seasonal use of nitarsone. Methods: We evaluated 3,329 participants ≥ 6 years old from the 2003–2010 National Health and Nutrition Examination Survey (NHANES) with urine arsenic available and undetectable urine arsenobetaine levels. Geometric mean ratios (GMR) of urine total arsenic and DMA were compared across increasing levels of poultry intake. Results: After adjustment, participants in the highest quartile of poultry consumption had urine total arsenic 1.12 (95% CI: 1.04, 1.22) and DMA 1.13 (95% CI: 1.06, 1.20) times higher than nonconsumers. During the fall/winter, participants in the highest quartile of turkey intake had urine total arsenic and DMA 1.17 (95% CI: 0.99, 1.39; p-trend = 0.02) and 1.13 (95% CI: 0.99, 1.30; p-trend = 0.03) times higher, respectively, than nonconsumers. Consumption of turkey during the past 24 hr was not associated with total arsenic or DMA during the spring/summer. Conclusions: Poultry intake was associated with increased urine total arsenic and DMA in NHANES 2003–2010, reflecting arsenic exposure. Seasonally stratified analyses by poultry type provide strong suggestive evidence that the historical use of arsenic-based poultry drugs contributed to arsenic exposure in the U.S. population. Citation: Nigra AE, Nachman KE, Love DC, Grau-Perez M, Navas-Acien A. 2017. Poultry consumption and arsenic exposure in the U.S. population. Environ Health Perspect 125:370–377; http://dx.doi.org/10.1289/EHP351 PMID:27735790

Poultry Consumption and Arsenic Exposure in the U.S. Population.

PubMed

Nigra, Anne E; Nachman, Keeve E; Love, David C; Grau-Perez, Maria; Navas-Acien, Ana

2017-03-01

Arsenicals (roxarsone and nitarsone) used in poultry production likely increase inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and roxarsone or nitarsone concentrations in poultry meat. However, the association between poultry intake and exposure to these arsenic species, as reflected in elevated urinary arsenic concentrations, is unknown. Our aim was to evaluate the association between 24-hr dietary recall of poultry consumption and arsenic exposure in the U.S. population. We hypothesized first, that poultry intake would be associated with higher urine arsenic concentrations and second, that the association between turkey intake and increased urine arsenic concentrations would be modified by season, reflecting seasonal use of nitarsone. We evaluated 3,329 participants ≥ 6 years old from the 2003-2010 National Health and Nutrition Examination Survey (NHANES) with urine arsenic available and undetectable urine arsenobetaine levels. Geometric mean ratios (GMR) of urine total arsenic and DMA were compared across increasing levels of poultry intake. After adjustment, participants in the highest quartile of poultry consumption had urine total arsenic 1.12 (95% CI: 1.04, 1.22) and DMA 1.13 (95% CI: 1.06, 1.20) times higher than nonconsumers. During the fall/winter, participants in the highest quartile of turkey intake had urine total arsenic and DMA 1.17 (95% CI: 0.99, 1.39; p -trend = 0.02) and 1.13 (95% CI: 0.99, 1.30; p -trend = 0.03) times higher, respectively, than nonconsumers. Consumption of turkey during the past 24 hr was not associated with total arsenic or DMA during the spring/summer. Poultry intake was associated with increased urine total arsenic and DMA in NHANES 2003-2010, reflecting arsenic exposure. Seasonally stratified analyses by poultry type provide strong suggestive evidence that the historical use of arsenic-based poultry drugs contributed to arsenic exposure in the U.S. Nigra AE, Nachman KE, Love DC, Grau-Perez M, Navas-Acien A. 2017. Poultry consumption and arsenic exposure in the U.S. Environ Health Perspect 125:370-377; http://dx.doi.org/10.1289/EHP351.

Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ameer, Syeda Shegufta

Background: Exposure to inorganic arsenic increases the risk of cancer and non-malignant diseases. Inefficient arsenic metabolism is a marker for susceptibility to arsenic toxicity. Arsenic may alter gene expression, possibly by altering DNA methylation. Objectives: To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism. Methods: The study participants, women from the Andes, Argentina, were exposed to arsenic via drinking water. Arsenic exposure was assessed as the sum of arsenic metabolites in urine (U-As), using high performance liquid-chromatography hydride-generation inductively-coupled-plasma-mass-spectrometry, and arsenic metabolism efficiency was assessed by themore » urinary fractions (%) of the individual metabolites. Genome-wide gene expression (N = 80 women) and DNA methylation (N = 93; 80 overlapping with gene expression) in peripheral blood were measured using Illumina DirectHyb HumanHT-12 v4.0 and Infinium Human-Methylation 450K BeadChip, respectively. Results: U-As concentrations, ranging 10–1251 μg/L, was associated with decreased gene expression: 64% of the top 1000 differentially expressed genes were down-regulated with increasing U-As. U-As was also associated with hypermethylation: 87% of the top 1000 CpGs were hypermethylated with increasing U-As. The expression of six genes and six individual CpG sites were significantly associated with increased U-As concentration. Pathway analyses revealed enrichment of genes related to cell death and cancer. The pathways differed somewhat depending on arsenic metabolism efficiency. We found no overlap between arsenic-related gene expression and DNA methylation for individual genes. Conclusions: Increased arsenic exposure was associated with lower gene expression and hypermethylation in peripheral blood, but with no evident overlap. - Highlights: • Women exposed to inorganic arsenic were studied for molecular responses in blood. • Arsenic is associated with decreased gene expression and increased DNA methylation. • Arsenic related pathways differed to some extent due to arsenic metabolism efficiency.« less

Walk-through survey report: Control technology for integrated circuit fabrication, Xerox Corporation, El Segundo, California

NASA Astrophysics Data System (ADS)

Mihlan, G. J.; Ungers, L. J.; Smith, R. K.; Mitchell, R. I.; Jones, J. H.

1983-05-01

A preliminary control technology assessment survey was conducted at the facility which manufactures N-channel metal oxide semiconductor (NMOS) integrated circuits. The facility has industrial hygiene review procedures for evaluating all new and existing process equipment. Employees are trained in safety, use of personal protective equipment, and emergency response. Workers potentially exposed to arsenic are monitored for urinary arsenic levels. The facility should be considered a candidate for detailed study based on the diversity of process operations encountered and the use of state-of-the-art technology and process equipment.

The possible role of direct ingestion on the overall absorption of cadmium or arsenic in workers exposed to CdO or As2O3 dust.

PubMed

Roels, H; Buchet, J P; Truc, J; Croquet, F; Lauwerys, R

1982-01-01

Six volunteers (two office and four cadmium (Cd)-exposed workers, all nonsmokers) from an electric condenser factory participated in a study involving the measurement of cadmium in air and in dust, the evaluation of hand and mouth contamination by cadmium, and the determination of fecal cadmium. The mean levels of total airborne cadmium measured with static and personal samplers were for the exposed workers 9.5 and 16.7 microgram/m3, respectively, and for the office workers 0.3 and 0.5 microgram/m3, respectively. In the office workers, hand contamination by Cd hardly changes over the workday (less than 10 microgram/hand), whereas in the exposed workers important hand contamination by Cd was observed (up to 1,200 microgram/hand during the workday and up to 300 microgram/hand before lunch or before leaving the factory). Mouth contamination by Cd is rather similar in both groups on Monday morning, but increases 20- to 50-fold on Friday afternoon in the Cd workers against a slight increase for the office workers. The concentration of Cd in the feces was not much different between Sunday and Friday in the office workers, whereas in the exposed workers it was higher on Friday than on Sunday. There is suggestive evidence from a comparative study of fecal cadmium in two Cd-exposed volunteers who carried out their jobs with and without gloves that direct cadmium intake from hand contamination may contribute to the overall Cd absorption. A limited study in a glassware factory (As2O3 exposure) involving the measurement of total airborne arsenic, the determination of urinary arsenic, and the evaluation of hand and mouth contamination by arsenic before and after the workshift suggests that the high urinary arsenic levels (300 microgram/g creatinine) are likely to be more related to an increased oral intake from contaminated hands than to an increased absorption from the lungs.

Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muñoz, Alexandra; Chervona, Yana; Hall, Megan

Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung and bladder cancers, and cardiovascular disease. Recent research indicates that arsenic may be an endocrine disruptor. This study was conducted to evaluate the nature of gene expression changes among males and females exposed to arsenic contaminated water in Bangladesh at high and low doses. Twenty-nine (55% male) Bangladeshi adults with water arsenic exposure ranging from 50 to 1000 μg/L were selected from the Folic Acid Creatinine Trial. RNA was extracted from peripheral blood mononuclear cells for gene expression profiling using Affymetrix 1.0 ST arrays.more » Differentially expressed genes were assessed between high and low exposure groups for males and females separately and findings were validated using quantitative real-time PCR. There were 534 and 645 differentially expressed genes (p < 0.05) in the peripheral blood mononuclear cells of males and females, respectively, when high and low water arsenic exposure groups were compared. Only 43 genes overlapped between the two sexes, with 29 changing in opposite directions. Despite the difference in gene sets both males and females exhibited common biological changes including deregulation of 17β-hydroxysteroid dehydrogenase enzymes, deregulation of genes downstream of Sp1 (specificity protein 1) transcription factor, and prediction of estrogen receptor alpha as a key hub in cardiovascular networks. Arsenic-exposed adults exhibit sex-specific gene expression profiles that implicate involvement of the endocrine system. Due to arsenic's possible role as an endocrine disruptor, exposure thresholds for arsenic may require different parameters for males and females. - Highlights: • Males and females exhibit unique gene expression changes in response to arsenic. • Only 23 genes are common among the differentially expressed genes for the sexes. • Male and female gene lists exhibit common biological implications. • Both sexes exhibit deregulation of cardiovascular and endocrine pathways.« less

Ultra-Shallow Depth Profiling of Arsenic Implants in Silicon by Hydride Generation-Inductively Coupled Plasma Atomic Emission Spectrometry

NASA Astrophysics Data System (ADS)

Matsubara, Atsuko; Kojima, Hisao; Itoga, Toshihiko; Kanehori, Keiichi

1995-08-01

High resolution depth profiling of arsenic (As) implanted into silicon wafers by a chemical technique is described. Silicon wafers are precisely etched through repeated oxidation by hydrogen peroxide solution and dissolution of the oxide by hydrofluoric acid solution. The etched silicon thickness is determined by inductively-coupled plasma atomic emission spectrometry (ICP-AES). Arsenic concentration is determined by hydride generation ICP-AES (HG-ICP-AES) with prereduction using potassium iodide. The detection limit of As in a 4-inch silicon wafer is 2.4×1018 atoms/cm3. The etched silicon thickness is controlled to less than 4±2 atomic layers. Depth profiling of an ultra-shallow As diffusion layer with the proposed method shows good agreement with profiling using the four-probe method or secondary ion mass spectrometry.

[Health risk for the vulnerable population exposed to arsenic in the province of Buenos Aires, Argentina].

PubMed

Navoni, Julio A; De Pietri, Diana; Garcia, Susana; Villaamil Lepori, Edda C

2012-01-01

To analyze the concentration of arsenic in water collected in localities of the province of Buenos Aires, Argentina, and the epidemiological relationship of that concentration to factors of susceptibility and associated pathologies. In 152 samples from 52 localities of Buenos Aires from 2003-2008, the concentration of arsenic was quantified through the generation of hydride spectrophotometry of atomic absorption. A composite index of health (CIH) was constructed using the content of arsenic and the percentages of households with unmet basic needs and dwellings without access to the potable water. Through the CIH, risk areas associated with mortality from malignant neoplasms related to arsenic were defined. Concentrations of arsenic spanned a broad range from 0.3 to 187 mg/L, with a median of 40 mg/L. Of the samples, 82% presented levels of arsenic higher than the acceptable limit of 10 mg/L, and more than half of those came from households with potable water connections. In the departments studied, the average mortality (deaths/100 000 inhabitants) from tumors was greater in men than in women: respiratory tract (310 versus 76), urinary tract (44 versus 11), and skin (21 versus 11), respectively. The regions with greater concentrations of arsenic and of poverty, together with the lack of potable water connections, had a two-to-four times greater risk. The findings from the composite index of health summarized the health risk from exposure to arsenic for lower socioeconomic levels of the population for a broad area of the province of Buenos Aires.

Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality.

PubMed

Shih, Yu-Hsuan; Islam, Tariqul; Hore, Samar Kumar; Sarwar, Golam; Shahriar, Mohammad Hasan; Yunus, Mohammad; Graziano, Joseph H; Harjes, Judith; Baron, John A; Parvez, Faruque; Ahsan, Habibul; Argos, Maria

2017-10-01

Chronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established. We evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh. Creatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality. We observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure. Prospective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age. Copyright © 2017 Elsevier Inc. All rights reserved.

Field Evaluation Of Arsenic Transport Across The Ground Water/Surface Water Interface: Speciation In Sediment Material

EPA Science Inventory

The solubility and mobility of arsenic in ground water are influenced by a variety of processes in the northeastern US subjective to geogenic and anthropogenic sources. This presentation will discuss the speciation of arsenic in sediment profiles resulting from ground water disc...

Health hazards and mitigation of chronic poisoning from arsenic in drinking water: Taiwan experiences.

PubMed

Chen, Chien-Jen

2014-01-01

There are two endemic areas of long-term exposure to arsenic from drinking water in Taiwan. Residents in the southwestern and northeastern endemic areas started using high-arsenic artesian well water in the early 1910s and late 1940s, respectively. Public water supply system using surface water was implemented in southwestern and northeastern endemic areas in the 1970s and 1990s, respectively. Systemic health hazards of long-term exposure to arsenic in drinking water have been intensively investigated since the 1960s, especially after 1985 in Taiwan. Several diseases have been well documented to be associated with chronic arsenic poisoning from drinking water showing a dose-response relation. They include characteristic skin lesions like hyperpigmentation or depigmentation, hyperkeratosis in palms and soles, and Bowen disease, peripheral vascular disease (specifically blackfoot disease), ischemic heart disease, cerebral infarction, microvascular diseases, abnormal peripheral microcirculation, carotid atherosclerosis, QT prolongation and increased dispersion in electrocardiography, hypertension, goiter, diabetes mellitus, cataract (specifically posterior subcapsular lens opacity), pterygium, slow neural conduction, retarded neurobehavioral development, erectile dysfunction, and cancers of the skin, lung, urinary bladder, kidney, and liver. The method of choice to mitigate arsenic poisoning through drinking water is to use safe drinking water from uncontaminated sources.

Association of hypothyroidism with low-level arsenic exposure in rural West Texas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gong, Gordon, E-mail: gordon.gong@ttuhsc.edu; Basom, Janet; Department of Family and Community Medicine, Texas Tech University Health Sciences Center, Lubbock, TX

It has been reported recently that a higher airborne arsenic level was correlated with higher urinary arsenic concentration and lower serum thyroxin level among urban policemen and rural highway workmen in Italy. The current study was to determine whether exposure to low-level arsenic groundwater (2–22 µg/L) is associated with hypothyroidism among 723 participants (118 male and 267 female Hispanics; 108 male and 230 female non-Hispanic whites, NHW) living in rural West Texas counties. Arsenic and iodine levels in their groundwater used for drinking and or cooking were estimated by the inverse distance weighted (IDW) interpolation technique. Groundwater arsenic was ≥8more » µg/L in 36% of the subjects' wells while iodine concentration was <1 µg/L in 91% of their wells. Logistic regression analysis showed that arsenic in groundwater ≥8 µg/L and cumulative arsenic exposure (groundwater arsenic concentration multiplied by the number of years living in the current address) but not groundwater iodine concentration were significant predictors for hypothyroidism among Hispanics (p<0.05) but not NHW after adjusting for covariates such as age, gender, annual household income and health insurance coverage. The ethnic difference may be due to a marginally higher percentage of Hispanics (p=0.0622) who lived in areas with groundwater arsenic ≥8 µg/L compared with NHW. The prevalence of hypothyroidism was significantly higher in Hispanics or NHW of this rural cohort than the national prevalence. Measures should be taken to reduce arsenic in drinking water in order to prevent hypothyroidism in rural areas. - Highlights: • We determined if arsenic exposure is associated with hypothyroidism in rural Texas. • Groundwater arsenic level is associated with hypothyroidism among Hispanics only. • The rate of hypothyroidism in rural Texas was higher than the US general population.« less

Association between lifetime exposure to inorganic arsenic in drinking water and coronary heart disease in Colorado residents.

PubMed

James, Katherine A; Byers, Tim; Hokanson, John E; Meliker, Jaymie R; Zerbe, Gary O; Marshall, Julie A

2015-02-01

Chronic diseases, including coronary heart disease (CHD), have been associated with ingestion of drinking water with high levels of inorganic arsenic (> 1,000 μg/L). However, associations have been inconclusive in populations with lower levels (< 100 μg/L) of inorganic arsenic exposure. We conducted a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of CHD. This study included 555 participants with 96 CHD events diagnosed between 1984 and 1998 for which individual lifetime arsenic exposure estimates were determined using data from structured interviews and secondary data sources to determine lifetime residence, which was linked to a geospatial model of arsenic concentrations in drinking water. These lifetime arsenic exposure estimates were correlated with historically collected urinary arsenic concentrations. A Cox proportional-hazards model with time-dependent CHD risk factors was used to assess the association between time-weighted average (TWA) lifetime exposure to low-level inorganic arsenic in drinking water and incident CHD. We estimated a positive association between low-level inorganic arsenic exposure and CHD risk [hazard ratio (HR): = 1.38, 95% CI: 1.09, 1.78] per 15 μg/L while adjusting for age, sex, first-degree family history of CHD, and serum low-density lipoprotein levels. The risk of CHD increased monotonically with increasing TWAs for inorganic arsenic exposure in water relative to < 20 μg/L (HR = 1.2, 95% CI: 0.6, 2.2 for 20-30 μg/L; HR = 2.2; 95% CI: 1.2, 4.0 for 30-45 μg/L; and HR = 3, 95% CI: 1.1, 9.1 for 45-88 μg/L). Lifetime exposure to low-level inorganic arsenic in drinking water was associated with increased risk for CHD in this population.

DNA damage in Mexican children living in high-risk contaminated scenarios.

PubMed

Jasso-Pineda, Yolanda; Díaz-Barriga, Fernando; Yáñez-Estrada, Leticia; Pérez-Vázquez, Francisco Javier; Pérez-Maldonado, Ivan Nelinho

2015-06-15

The aim of this study was to evaluate the deoxyribonucleic acid (DNA) damage (as a biomarker of biological effects) in children living in areas at high risk of contamination in Mexico using the comet assay. The alkaline comet assay was performed in order to assess DNA damage levels in blood cells of 276 children living in eleven communities in four states of Mexico. Moreover, levels of arsenic and 1-hydroxypyrene (1-OHP) in urine and lead and total DDT [sum of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT)] in blood were quantified. We found urinary 1-OHP levels between

Histopathology of Cervical Cancer and Arsenic Concentration in Well Water: An Ecological Analysis.

PubMed

Mostafa, Mohammad Golam; Queen, Zarat Jahin; Cherry, Nicola

2017-10-06

Arsenic in drinking water is causally linked with cancer of the skin, lung, and urinary bladder, but there is very little data on a possible role for arsenic in the etiology of cervical cancer, a disease in which human papilloma virus is held to be a necessary but not sufficient cause. All histopathology results from cervical specimens from the National Institute of Cancer Research and Hospital (NICRH), Dhaka (1997-2015), and the Anowara Medical Services (2003-2015), both serving the whole of Bangladesh, were classified by cell type. Arsenic concentrations in well water in the thana of residence were estimated from systematic sampling carried out by the British Geological Survey. In a case-referent analysis arsenic estimates for cases of cervical cancer were compared with those found to have benign lesions. In this study, 3464 NICRH (CH) cervical specimens and 30,050 community medical service (CMS) specimens were available: 3329 (CH) and 899 (CMS) were recorded as malignant. Most were squamous cell carcinoma, of which 4.9% were poorly differentiated. Overall, there was no increase in cervical cancer with increasing arsenic concentration. Among those with squamous cell histology, a strong dose response was seen for poorly differentiated cancer with increasing arsenic exposure. The odds ratio increased monotonically, compared with exposure <10 μg/L, from 1.58 at 10 < 50 μg/L to 8.11 at >200 μg/L (p < 0.001). Given the high proportion of Bangladeshis using drinking water containing >50 μg/L of arsenic, the evidence that arsenic is implicated in cancer grade suggests a need for further investigation and the introduction of cervical screening in high arsenic areas.

A concurrent exposure to arsenic and fluoride from drinking water in Chihuahua, Mexico.

PubMed

González-Horta, Carmen; Ballinas-Casarrubias, Lourdes; Sánchez-Ramírez, Blanca; Ishida, María C; Barrera-Hernández, Angel; Gutiérrez-Torres, Daniela; Zacarias, Olga L; Saunders, R Jesse; Drobná, Zuzana; Mendez, Michelle A; García-Vargas, Gonzalo; Loomis, Dana; Stýblo, Miroslav; Del Razo, Luz M

2015-04-24

Inorganic arsenic (iAs) and fluoride (F-) are naturally occurring drinking water contaminants. However, co-exposure to these contaminants and its effects on human health are understudied. The goal of this study was examined exposures to iAs and F- in Chihuahua, Mexico, where exposure to iAs in drinking water has been associated with adverse health effects. All 1119 eligible Chihuahua residents (>18 years) provided a sample of drinking water and spot urine samples. iAs and F- concentrations in water samples ranged from 0.1 to 419.8 µg As/L and from 0.05 to 11.8 mg F-/L. Urinary arsenic (U-tAs) and urinary F- (U-F-) levels ranged from 0.5 to 467.9 ng As/mL and from 0.1 to 14.4 µg F-/mL. A strong positive correlation was found between iAs and F- concentrations in drinking water (rs = 0.741). Similarly, U-tAs levels correlated positively with U-F- concentrations (rs = 0.633). These results show that Chihuahua residents exposed to high iAs concentrations in drinking water are also exposed to high levels of F-, raising questions about possible contribution of F- exposure to the adverse effects that have so far been attributed only to iAs exposure. Thus, investigation of possible interactions between iAs and F- exposures and its related health risks deserves immediate attention.

Prolonged environmental exposure of arsenic through drinking water on the risk of hypertension and type 2 diabetes.

PubMed

Li, Xin; Li, Bing; Xi, Shuhua; Zheng, Quanmei; Lv, Xiuqiang; Sun, Guifan

2013-11-01

Prolonged exposure to inorganic arsenic has been a severe environmental public health issue worldwide in the recent decades. Increasing evidence has suggested a possible role of prolonged arsenic exposure through drinking water in the development of arsenic-induced chronic noncancer diseases, among which hypertension and type 2 diabetes (T2D) are the focus of concern. Although exposure to high levels of arsenic has been reported to be associated with excess risk of hypertension or T2D in a dose-dependent manner, the association has yet to be established, especially low-level exposure. This cross-sectional study was designed to evaluate the potential association between prolonged environmental arsenic exposure through drinking water and the prevalence of hypertension and T2D in Inner Mongolia, China, with emphasis on the assessment of low-level exposure. In this study (a total of 669 men and women), we found that the blood pressure levels were significantly correlated with cumulative arsenic exposure and that the systolic blood pressure of the subjects with arsenic exposure>50 μg/L was significantly higher than those of the subjects with <10 and 10-50 μg/L exposure. Significant prevalence of hypertension was found in the subjects of the >50 μg/L group both before and after adjustment for confounders. In addition, a significant negative relationship was found between urinary arsenic percentage of dimethylated arsenic (DMA%) and the prevalence of hypertension in the >50 μg/L group. However, low-level arsenic exposure (10-50 μg/L) was not statistically associated with hypertension. No significant difference of blood glucose was found among the groups with different arsenic exposure levels. No statistical association was found between arsenic exposure and T2D. Our findings suggested that prolonged arsenic exposure might play a role in the development of hypertension; however, only high-level arsenic was associated with the risk of hypertension. Our findings also indicated that lower DMA% might be related with the increased susceptibility of arsenic-induced hypertension.

Inorganic arsenic exposure increased expression of Fas and Bax gene in vivo and vitro.

PubMed

He, Yuefeng; Zhang, Ruobing; Xiaoxiao, Song; Li, Shang; Xinan, Wu; Huang, Dahai

2018-06-01

Accumulating evidences have shown that apoptosis plays an important role in mediating the therapeutic effects and toxicity of arsenic. Fas and Bax genes are critical regulatory genes for apoptosis. In this study, we investigated the association between levels of Fas and Bax expression and the three arsenic species (inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in vivo and vitro. Three arsenic species in urine were measured and levels of Fas and Bax expression were examined by the quantitative real-time PCR (qPCR) for all subjects. We found that Fas and Bax mRNA expression in the exposed group were significantly higher than that in the control group. The levels of gene expression were positively correlated with the concentrations of urinary iAs, MMA and DMA in all subjects. Sodium arsenite induced Fas and Bax mRNA expression, then MMA and DMA did not induce mRNA expression in MDA-MB-231 and XWLC-05 cells. The findings of the present study indicated that iAs, MMA, and DMA had different effects on expression of Bax and Fas gene. Copyright © 2017. Published by Elsevier B.V.

GENE EXPRESSION PROFILING OF HYPERKERATOTIC SKIN FROM INNER MONGOLIANS CHRONICALLY EXPOSED TO ARSENIC

EPA Science Inventory

Millions of people worldwide have been chronically exposed to arsenic levels in drinking water that greatly exceed the current World Health Organization¿s recommended limit of 10 µg/ml. The skin is a major target of arsenic toxicity, and some of the first clinical signs of chroni...

Low-level arsenic exposure: nutritional and dietary predictors in first-grade Uruguayan children

PubMed Central

Kordas, Katarzyna; Queirolo, Elena I; Mañay, Nelly; Peregalli, Fabiana; Hsiao, Pao Ying; Lu, Ying; Vahter, Marie

2016-01-01

Arsenic exposure in children is a public health concern but is understudied in relation to the predictors, and effects of low-level exposure. We examined the extent and dietary predictors of exposure to inorganic arsenic in 5–8 year old children from Montevideo, Uruguay. Children were recruited at school; 357 were enrolled, 328 collected morning urine samples, and 317 had two 24-hour dietary recalls. Urinary arsenic metabolites, i.e. inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA), were measured using high-performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICP-MS), and the sum concentration (U-As) used for exposure assessment. Proportions of arsenic metabolites (%iAs, %MMA and %DMA) in urine were modelled in OLS regressions as functions of food groups, dietary patterns, nutrient intake, and nutritional status. Exposure to arsenic was low (median U-As: 9.9 µg/L) and household water (water As: median 0.45 µg/L) was not a major contributor to exposure. Children with higher consumption of rice had higher U-As but lower %iAs, %MMA, and higher %DMA. Children with higher meat consumption had lower %iAs and higher %DMA. Higher scores on ”nutrient dense” dietary pattern were related to lower %iAs and %MMA, and higher %DMA. Higher intake of dietary folate was associated with lower %MMA and higher %DMA. Overweight children had lower %MMA and higher %DMA than normal-weight children. In summary, rice was an important predictor of exposure to inorganic arsenic and DMA. Higher meat and folate consumption, diet rich in green leafy and red-orange vegetables and eggs, and higher BMI contributed to higher arsenic methylation capacity. PMID:26828624

Low-level arsenic exposure: Nutritional and dietary predictors in first-grade Uruguayan children.

PubMed

Kordas, Katarzyna; Queirolo, Elena I; Mañay, Nelly; Peregalli, Fabiana; Hsiao, Pao Ying; Lu, Ying; Vahter, Marie

2016-05-01

Arsenic exposure in children is a public health concern but is understudied in relation to the predictors, and effects of low-level exposure. We examined the extent and dietary predictors of exposure to inorganic arsenic in 5-8 year old children from Montevideo, Uruguay. Children were recruited at school; 357 were enrolled, 328 collected morning urine samples, and 317 had two 24-h dietary recalls. Urinary arsenic metabolites, i.e. inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA), were measured using high-performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICP-MS), and the sum concentration (U-As) used for exposure assessment. Proportions of arsenic metabolites (%iAs, %MMA and %DMA) in urine were modelled in OLS regressions as functions of food groups, dietary patterns, nutrient intake, and nutritional status. Exposure to arsenic was low (median U-As: 9.9µg/L) and household water (water As: median 0.45µg/L) was not a major contributor to exposure. Children with higher consumption of rice had higher U-As but lower %iAs, %MMA, and higher %DMA. Children with higher meat consumption had lower %iAs and higher %DMA. Higher scores on "nutrient dense" dietary pattern were related to lower %iAs and %MMA, and higher %DMA. Higher intake of dietary folate was associated with lower %MMA and higher %DMA. Overweight children had lower %MMA and higher %DMA than normal-weight children. In summary, rice was an important predictor of exposure to inorganic arsenic and DMA. Higher meat and folate consumption, diet rich in green leafy and red-orange vegetables and eggs, and higher BMI contributed to higher arsenic methylation capacity. Copyright © 2016 Elsevier Inc. All rights reserved.

Prenatal Arsenic Exposure and DNA Methylation in Maternal and Umbilical Cord Blood Leukocytes

PubMed Central

Baccarelli, Andrea; Hoffman, Elaine; Tarantini, Letizia; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Hsueh, Yu-Mei; Wright, Robert O.; Christiani, David C.

2012-01-01

Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming. Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes. Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure. Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: < 1–230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation. Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects. PMID:22466225

Biologically based modeling of multimedia, multipathway, multiroute population exposures to arsenic

PubMed Central

Georgopoulos, Panos G.; Wang, Sheng-Wei; Yang, Yu-Ching; Xue, Jianping; Zartarian, Valerie G.; Mccurdy, Thomas; Özkaynak, Halûk

2011-01-01

This article presents an integrated, biologically based, source-to-dose assessment framework for modeling multimedia/multipathway/multiroute exposures to arsenic. Case studies demonstrating this framework are presented for three US counties (Hunderton County, NJ; Pima County, AZ; and Franklin County, OH), representing substantially different conditions of exposure. The approach taken utilizes the Modeling ENvironment for TOtal Risk studies (MENTOR) in an implementation that incorporates and extends the approach pioneered by Stochastic Human Exposure and Dose Simulation (SHEDS), in conjunction with a number of available databases, including NATA, NHEXAS, CSFII, and CHAD, and extends modeling techniques that have been developed in recent years. Model results indicate that, in most cases, the food intake pathway is the dominant contributor to total exposure and dose to arsenic. Model predictions are evaluated qualitatively by comparing distributions of predicted total arsenic amounts in urine with those derived using biomarker measurements from the NHEXAS — Region V study: the population distributions of urinary total arsenic levels calculated through MENTOR and from the NHEXAS measurements are in general qualitative agreement. Observed differences are due to various factors, such as interindividual variation in arsenic metabolism in humans, that are not fully accounted for in the current model implementation but can be incorporated in the future, in the open framework of MENTOR. The present study demonstrates that integrated source-to-dose modeling for arsenic can not only provide estimates of the relative contributions of multipathway exposure routes to the total exposure estimates, but can also estimate internal target tissue doses for speciated organic and inorganic arsenic, which can eventually be used to improve evaluation of health risks associated with exposures to arsenic from multiple sources, routes, and pathways. PMID:18073786

Contribution of inorganic arsenic sources to population exposure risk on a regional scale.

PubMed

Chou, Wei-Chun; Chen, Jein-Wen; Liao, Chung-Min

2016-07-01

Chronic exposure to inorganic arsenic (iAs) in the human population is associated with various internal cancers and other adverse outcomes. The purpose of this study was to estimate a population-scale exposure risk attributable to iAs consumptions by linking a stochastic physiological-based pharmacokinetic (PBPK) model and biomonitoring data of iAs in urine. The urinary As concentrations were obtained from a total of 1,043 subjects living in an industrial area of Taiwan. The results showed that the study subjects had an iAs exposure risk of 27 % (the daily iAs intake for 27 % study subjects exceeded the WHO-recommended value, 2.1 μg iAs day(-1) kg(-1) body weight). Moreover, drinking water and cooked rice contributed to the iAs exposure risk by 10 and 41 %, respectively. The predicted risks in the current study were 4.82, 27.21, 34.69, and 64.17 %, respectively, among the mid-range of Mexico, Taiwan (this study), Korea, and Bangladesh reported in the literature. In conclusion, we developed a population-scale-based risk model that covered the broad range of iAS exposure by integrating stochastic PBPK modeling and reverse dosimetry to generate probabilistic distribution of As intake corresponding to urinary As measured from the cohort study. The model can also be updated as new urinary As information becomes available.

Comparison of the Health Implications on the Use of As and Cd Contaminated Water Supply between Urban and Rural Communities

PubMed Central

Zailina, H.; Najibah, H.; Nadia Aiezzati, A.; Praveena, S. M.; Patimah, I.

2014-01-01

A cross-sectional study was carried out to determine the arsenic (As) and cadmium (Cd) concentrations in blood, urine, and drinking water as well as the health implications on 100 residents in an urban and a rural community. Results showed the blood As, urinary Cd, DNA damage, and water As and Cs were significantly (P < 0.001) higher in the rural community. Findings showed significant (P < 0.005) correlations between blood As and DNA damage with household income, years of residence, and total glasses of daily water consumption among the rural residents. The urinary NAG concentrations, years of residence, milk powder intake (glass/week), and seafood intake (per week) were significantly correlated (P < 0.005) with urinary Cd concentrations among respondents. In addition, urinary Cd level significantly influenced the urinary NAG concentrations (P < 0.001). The rural respondents experienced significantly higher lymphocyte DNA damage and blood As influenced by their years of residence and water consumption. The Cd in drinking water also resulted in the rural respondents having significantly higher urinary NAG which had a significant relationship with urinary Cd. PMID:25530970

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agusa, Tetsuro; Department of Legal Medicine, Shimane University Faculty of Medicine, Enya 89-1, Izumo 693-8501; Iwata, Hisato

To elucidate the role of genetic factors in arsenic (As) metabolism, we studied associations of single nucleotide polymorphisms (SNPs) in As (+ 3 oxidation state) methyltransferase (AS3MT) with the As concentrations in hair and urine, and urinary As profile in residents in the Red River Delta, Vietnam. Concentrations of total As in groundwater were 0.7-502 {mu}g/l. Total As levels in groundwater drastically decreased by using sand filter, indicating that the filter could be effective to remove As from raw groundwater. Concentrations of inorganic As (IAs) in urine and total As in hair of males were higher than those of females.more » A significant positive correlation between monomethylarsonic acid (MMA)/IAs and age in females indicates that older females have higher methylation capacity from IAs to MMA. Body mass index negatively correlated with urinary As concentrations in males. Homozygote for SNPs 4602AA, 35991GG, and 37853GG, which showed strong linkage disequilibrium (LD), had higher percentage (%) of dimethylarsinic acid (DMA) in urine. SNPs 4740 and 12590 had strong LD and associated with urinary %DMA. Although SNPs 6144, 12390, 14215, and 35587 comprised LD cluster, homozygotes in SNPs 12390GG and 35587CC had lower DMA/MMA in urine, suggesting low methylation capacity from MMA to DMA in homo types for these SNPs. SNPs 5913 and 8973 correlated with %MMA and %DMA, respectively. Heterozygote for SNP 14458TC had higher MMA/IAs in urine than TT homozygote, indicating that the heterozygote may have stronger methylation ability of IAs. To our knowledge, this is the first study on the association of genetic factors with As metabolism in Vietnamese.« less

Folate and Cobalamin Modify Associations between S-adenosylmethionine and Methylated Arsenic Metabolites in Arsenic-Exposed Bangladeshi Adults123

PubMed Central

Howe, Caitlin G.; Niedzwiecki, Megan M.; Hall, Megan N.; Liu, Xinhua; Ilievski, Vesna; Slavkovich, Vesna; Alam, Shafiul; Siddique, Abu B.; Graziano, Joseph H.; Gamble, Mary V.

2014-01-01

Chronic exposure to inorganic arsenic (InAs) through drinking water is a major problem worldwide. InAs undergoes hepatic methylation to form mono- and dimethyl arsenical species (MMA and DMA, respectively), facilitating arsenic elimination. Both reactions are catalyzed by arsenic (+3 oxidation state) methyltransferase (AS3MT) using S-adenosylmethionine (SAM) as the methyl donor, yielding the methylated product and S-adenosylhomocysteine (SAH), a potent product-inhibitor of AS3MT. SAM biosynthesis depends on folate- and cobalamin-dependent one-carbon metabolism. With the use of samples from 353 participants in the Folate and Oxidative Stress Study, our objective was to test the hypotheses that blood SAM and SAH concentrations are associated with arsenic methylation and that these associations differ by folate and cobalamin nutritional status. Blood SAM and SAH were measured by HPLC. Arsenic metabolites in blood and urine were measured by HPLC coupled to dynamic reaction cell inductively coupled plasma MS. In linear regression analyses, SAH was not associated with any of the arsenic metabolites. However, log(SAM) was negatively associated with log(% urinary InAs) (β: −0.11; 95% CI: −0.19, −0.02; P = 0.01), and folate and cobalamin nutritional status significantly modified associations between SAM and percentage of blood MMA (%bMMA) and percentage of blood DMA (%bDMA) (P = 0.02 and P = 0.01, respectively). In folate- and cobalamin-deficient individuals, log(SAM) was positively associated with %bMMA (β: 6.96; 95% CI: 1.86, 12.05; P < 0.01) and negatively associated with %bDMA (β: −6.19; 95% CI: −12.71, 0.32; P = 0.06). These findings suggest that when exposure to InAs is high, and methyl groups are limiting, SAM is used primarily for MMA synthesis rather than for DMA synthesis, contributing additional evidence that nutritional status may explain some of the interindividual differences in arsenic metabolism and, consequently, susceptibility to arsenic toxicity. PMID:24598884

An investigation of the health effects caused by exposure to arsenic from drinking water and coal combustion: arsenic exposure and metabolism.

PubMed

Wei, Binggan; Yu, Jiangping; Kong, Chang; Li, Hairong; Yang, Linsheng; Guo, Zhiwei; Cui, Na; Xia, Yajuan; Wu, Kegong

2017-11-01

Few studies have been conducted to compare arsenic exposure, metabolism, and methylation in populations exposed to arsenic in drinking water and from coal combustion. Therefore, arsenic concentrations in the environment and arsenic speciation in the urine of subjects exposed to arsenic as a consequence of coal combustion in a rural area in Shaanxi province (CCA) and in drinking water in a rural area in Inner Mongolia (DWA) were investigated. The mean arsenic concentrations in drinking water, indoor air, and soil in CCA were 4.52 μg/L, 0.03 mg/m 3 , and 14.93 mg/kg, respectively. The mean arsenic concentrations in drinking water and soil in DWA were 144.71 μg/L and 10.19 mg/kg, respectively, while the level in indoor air was lower than the limit of detection. The total daily intakes of arsenic in DWA and CCA were 4.47 and 3.13 μg/day·kg, respectively. The mean urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsenic acid (DMA), and total arsenic (TAs) for subjects with skin lesions in DWA were 50.41, 47.01, 202.66, and 300.08 μg/L. The concentrations for subjects without skin lesions were 49.76, 44.20, 195.60, and 289.56 μg/L, respectively. The %iAs, %MMA, and %DMA in the TAs in the urine of subjects from CCA were 12.24, 14.73, and 73.03%, while the corresponding values from DWA were 17.54, 15.57, and 66.89%, respectively. The subjects in DWA typically had a higher %iAs and %MMA, and a lower %DMA, and primary and secondary methylation index (PMI and SMI) than the subjects in CCA. It was concluded that the arsenic methylation efficiency of subjects in DWA and CCA was significantly influenced by chronic exposure to high levels of arsenic in the environment. The lower PMI and SMI values in DWA revealed lower arsenic methylation capacity due to ingestion of arsenic in drinking water. However, it remained unclear if the differences in arsenic metabolism between the two groups were due to differences in exposure levels or in exposure route.

Association of Arsenic Methylation Capacity with Developmental Delays and Health Status in Children: A Prospective Case-Control Trial

NASA Astrophysics Data System (ADS)

Hsueh, Yu-Mei; Chen, Wei-Jen; Lee, Chih-Ying; Chien, Ssu-Ning; Shiue, Horng-Sheng; Huang, Shiau-Rung; Lin, Ming-I.; Mu, Shu-Chi; Hsieh, Ru-Lan

2016-11-01

This case-control study identified the association between the arsenic methylation capacity and developmental delays and explored the association of this capacity with the health status of children. We recruited 120 children with developmental delays and 120 age- and sex-matched children without developmental delays. The health status of the children was assessed using the Pediatric Quality of Life Inventory (PedsQL) and Pediatric Outcomes Data Collection Instrument (PODCI). The arsenic methylation capacity was determined by the percentages of inorganic arsenic (InAs%), monomethylarsonic acid (MMAV%), and dimethylarsinic acid (DMAV%) through liquid chromatography and hydride generation atomic absorption spectrometry. Developmental delays were significantly positively associated with the total urinary arsenic concentration, InAs%, and MMAV%, and was significantly negatively associated with DMAV% in a dose-dependent manner. MMAV% was negatively associated with the health-related quality of life (HRQOL; -1.19 to -1.46, P < 0.01) and functional performance (-0.82 to -1.14, P < 0.01), whereas DMAV% was positively associated with HRQOL (0.33-0.35, P < 0.05) and functional performance (0.21-0.39, P < 0.01-0.05) in all children and in those with developmental delays. The arsenic methylation capacity is dose-dependently associated with developmental delays and with the health status of children, particularly those with developmental delays.

A Concurrent Exposure to Arsenic and Fluoride from Drinking Water in Chihuahua, Mexico

PubMed Central

González-Horta, Carmen; Ballinas-Casarrubias, Lourdes; Sánchez-Ramírez, Blanca; Ishida, María C.; Barrera-Hernández, Angel; Gutiérrez-Torres, Daniela; Zacarias, Olga L.; Saunders, R. Jesse; Drobná, Zuzana; Mendez, Michelle A.; García-Vargas, Gonzalo; Loomis, Dana; Stýblo, Miroslav; Del Razo, Luz M.

2015-01-01

Inorganic arsenic (iAs) and fluoride (F−) are naturally occurring drinking water contaminants. However, co-exposure to these contaminants and its effects on human health are understudied. The goal of this study was examined exposures to iAs and F− in Chihuahua, Mexico, where exposure to iAs in drinking water has been associated with adverse health effects. All 1119 eligible Chihuahua residents (>18 years) provided a sample of drinking water and spot urine samples. iAs and F− concentrations in water samples ranged from 0.1 to 419.8 µg As/L and from 0.05 to 11.8 mg F−/L. Urinary arsenic (U-tAs) and urinary F− (U-F−) levels ranged from 0.5 to 467.9 ng As/mL and from 0.1 to 14.4 µg F−/mL. A strong positive correlation was found between iAs and F− concentrations in drinking water (rs = 0.741). Similarly, U-tAs levels correlated positively with U-F− concentrations (rs = 0.633). These results show that Chihuahua residents exposed to high iAs concentrations in drinking water are also exposed to high levels of F−, raising questions about possible contribution of F− exposure to the adverse effects that have so far been attributed only to iAs exposure. Thus, investigation of possible interactions between iAs and F− exposures and its related health risks deserves immediate attention. PMID:25918912

Arsenic microdistribution and speciation in toenail clippings of children living in a historic gold mining area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pearce, Dora C.; Dowling, Kim; Gerson, Andrea R.

2010-05-04

Arsenic is naturally associated with gold mineralization and elevated in some soils and mine waste around historical gold mining activity in Victoria, Australia. To explore uptake, arsenic concentrations in children's toenail clippings and household soils were measured, and the microdistribution and speciation of arsenic in situ in toenail clipping thin sections investigated using synchrotron-based X-ray microprobe techniques. The ability to differentiate exogenous arsenic was explored by investigating surface contamination on cleaned clippings using depth profiling, and direct diffusion of arsenic into incubated clippings. Total arsenic concentrations ranged from 0.15 to 2.1 {micro}g/g (n = 29) in clipping samples and frommore » 3.3 to 130 {micro}g/g (n = 22) in household soils, with significant correlation between transformed arsenic concentrations (Pearson's r = 0.42, P = 0.023) when household soil was treated as independent. In clipping thin sections (n = 2), X-ray fluorescence (XRF) mapping showed discrete layering of arsenic consistent with nail structure, and irregular arsenic incorporation along the nail growth axis. Arsenic concentrations were heterogeneous at 10 x 10 {micro}m microprobe spot locations investigated (< 0.1 to 13.3 {micro}g/g). X-ray absorption near-edge structure (XANES) spectra suggested the presence of two distinct arsenic species: a lower oxidation state species, possibly with mixed sulphur and methyl coordination (denoted As{sub (-S, -ch3)}{sup {approx}III}); and a higher oxidation state species (denoted As{sub (-O)}{sup {approx}V}). Depth profiling suggested that surface contamination was unlikely (n = 4), and XRF and XANES analyses of thin sections of clippings incubated in dry or wet mine waste, or untreated, suggested direct diffusion of arsenic occurred under moist conditions. These findings suggest that arsenic in soil contributes to some systemic absorption associated with periodic exposures among children resident in areas of historic gold mining activity in Victoria, Australia. Future studies are required to ascertain if adverse health effects are associated with current levels of arsenic uptake.« less

Health assessment for Anaconda Smelter Site, Anaconda, Deer Lodge County, Montana, Region 8. CERCLIS No. MTD093291656. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1987-02-05

The Environmental Protection Agency (EPA,) Region VIII has requested that the Agency for Toxic Substances and Disease Registry (ATSDR) evaluate the Remedial Investigation and Feasibility Study (RI/FS) Reports for the Mill Creek, Montana Anaconda Swelter Site. Extensive environmental sampling by EPA, urinary arsenic surveys conducted by the Centers for Disease Control, the Endangerment Assessment (EA,) and the RI have consistently shown extensive contamination of soils and house dust by arsenic, cadmium, and lead, and episodic contamination of drinking water with arsenic above the EPA Maximal Contaminant Level (MCL). The RI presents results of calculations showing, potentially, an elevated excess lifetimemore » risk of skin cancer for males from chronic exposure to arsenic by ingestion. The calculations were performed only for males, the most sensitive subpopulation; however, the female subpopulation would also be expected to have a lesser but elevated excess skin cancer risk from ingestion of arsenic. The long-term health effects of cadmium and lead are additional concerns. When EPA makes a Record of Decision (ROD) for the Mill Creek site, ATSDR can more readily make a definitive statement about the adequacy of the chosen Alternative for reducing the public health risk at Mill Creek.« less

Chronic arsenic exposure and risk of carotid artery disease: The Strong Heart Study.

PubMed

Mateen, Farrah J; Grau-Perez, Maria; Pollak, Jonathan S; Moon, Katherine A; Howard, Barbara V; Umans, Jason G; Best, Lyle G; Francesconi, Kevin A; Goessler, Walter; Crainiceanu, Ciprian; Guallar, Eliseo; Devereux, Richard B; Roman, Mary J; Navas-Acien, Ana

2017-08-01

Inorganic arsenic exposure from naturally contaminated groundwater is related to vascular disease. No prospective studies have evaluated the association between arsenic and carotid atherosclerosis at low-moderate levels. We examined the association of long-term, low-moderate inorganic arsenic exposure with carotid arterial disease. American Indians, 45-74 years old, in Arizona, Oklahoma, and North and South Dakota had arsenic concentrations (sum of inorganic and methylated species, μg/g urine creatinine) measured from baseline urine samples (1989-1991). Carotid artery ultrasound was performed in 1998-1999. Vascular disease was assessed by the carotid intima media thickness (CIMT), the presence of atherosclerotic plaque in the carotid, and by the number of segments containing plaque (plaque score). 2402 participants (mean age 55.3 years, 63.1% female, mean body mass index 31.0kg/m 2 , diabetes 45.7%, hypertension 34.2%) had a median (interquintile range) urine arsenic concentration of 9.2 (5.00, 17.06) µg/g creatinine. The mean CIMT was 0.75mm. 64.7% had carotid artery plaque (3% with >50% stenosis). In fully adjusted models comparing participants in the 80th vs. 20th percentile in arsenic concentrations, the mean difference in CIMT was 0.01 (95% confidence interval (95%CI): 0.00, 0.02) mm, the relative risk of plaque presence was 1.04 (95%CI: 0.99, 1.09), and the geometric mean ratio of plaque score was 1.05 (95%CI: 1.01, 1.09). Urine arsenic was positively associated with CIMT and increased plaque score later in life although the association was small. The relationship between urinary arsenic and the presence of plaque was not statistically significant when adjusted for other risk factors. Arsenic exposure may play a role in increasing the severity of carotid vascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Peripheral Arterial Disease and Its Association With Arsenic Exposure and Metabolism in the Strong Heart Study

PubMed Central

Newman, Jonathan D.; Navas-Acien, Ana; Kuo, Chin-Chi; Guallar, Eliseo; Howard, Barbara V.; Fabsitz, Richard R.; Devereux, Richard B.; Umans, Jason G.; Francesconi, Kevin A.; Goessler, Walter; Best, Lyle T.; Tellez-Plaza, Maria

2016-01-01

At high levels, inorganic arsenic exposure is linked to peripheral arterial disease (PAD) and cardiovascular disease. To our knowledge, no prior study has evaluated the association between low-to-moderate arsenic exposure and incident PAD by ankle brachial index (ABI). We evaluated this relationship in the Strong Heart Study, a large population-based cohort study of American Indian communities. A total of 2,977 and 2,966 PAD-free participants who were aged 45–74 years in 1989–1991 were reexamined in 1993–1995 and 1997–1999, respectively, for incident PAD defined as either ABI <0.9 or ABI >1.4. A total of 286 and 206 incident PAD cases were identified for ABI <0.9 and ABI >1.4, respectively. The sum of inorganic and methylated urinary arsenic species (∑As) at baseline was used as a biomarker of long-term exposure. Comparing the highest tertile of ∑As with the lowest, the adjusted hazard ratios were 0.57 (95% confidence interval (CI): 0.32, 1.01) for ABI <0.9 and 2.24 (95% CI: 1.01, 4.32) for ABI >1.4. Increased arsenic methylation (as percent dimethylarsinate) was associated with a 2-fold increased risk of ABI >1.4 (hazard ratio = 2.04, 95% CI: 1.02, 3.41). Long-term low-to-moderate ∑As and increased arsenic methylation were associated with ABI >1.4 but not with ABI <0.9. Further studies are needed to clarify whether diabetes and enhanced arsenic metabolism increase susceptibility to the vasculotoxic effects of arsenic exposure. PMID:27810857

Characterization of intracellular inclusions in the urothelium of mice exposed to inorganic arsenic.

PubMed

Dodmane, Puttappa R; Arnold, Lora L; Muirhead, David E; Suzuki, Shugo; Yokohira, Masanao; Pennington, Karen L; Dave, Bhavana J; Lu, Xiufen; Le, X Chris; Cohen, Samuel M

2014-01-01

Inorganic arsenic (iAs) is a known human carcinogen at high exposures, increasing the incidences of urinary bladder, skin, and lung cancers. In most mammalian species, ingested iAs is excreted mainly through urine primarily as dimethylarsinic acid (DMA(V)). In wild-type (WT) mice, iAs, DMA(V), and dimethylarsinous acid (DMA(III)) exposures induce formation of intramitochondrial urothelial inclusions. Arsenite (iAs(III)) also induced intranuclear inclusions in arsenic (+3 oxidation state) methyltransferase knockout (As3mt KO) mice. The arsenic-induced formation of inclusions in the mouse urothelium was dose and time dependent. The inclusions do not occur in iAs-treated rats and do not appear to be related to arsenic-induced urothelial cytotoxicity. Similar inclusions in exfoliated urothelial cells from humans exposed to iAs have been incorrectly identified as micronuclei. We have characterized the urothelial inclusions using transmission electron microscopy (TEM), DNA-specific 4',6-diamidino-2-phenylindole (DAPI), and non-DNA-specific Giemsa staining and determined the arsenical content. The mouse inclusions stained with Giemsa but not with the DAPI stain. Analysis of urothelial mitochondrial- and nuclear-enriched fractions isolated from WT (C57BL/6) and As3mt KO mice exposed to arsenate (iAs(V)) for 4 weeks showed higher levels of iAs(V) in the treated groups. iAs(III) was the major arsenical present in the enriched nuclear fraction from iAs(V)-treated As3mt KO mice. In conclusion, the urothelial cell inclusions induced by arsenicals appear to serve as a detoxifying sequestration mechanism similar to other metals, and they do not represent micronuclei.

TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ACUTE ORAL ADMINISTRATION OF ARSENATE

EPA Science Inventory

ABSTRACT The relationship of exposure dose and tissue concentration of parent chemical and metabolites is a critical issue in cases where toxicity may be mediated by a metabolite or parent chemical and metabolite acting together. This has emerged as an issue for inorganic ars...

Association of glutathione S-transferase Ω 1-1 polymorphisms (A140D and E208K) with the expression of interleukin-8 (IL-8), transforming growth factor beta (TGF-β), and apoptotic protease-activating factor 1 (Apaf-1) in humans chronically exposed to arsenic in drinking water.

PubMed

Escobar-García, D M; Del Razo, L M; Sanchez-Peña, L C; Mandeville, P B; Lopez-Campos, C; Escudero-Lourdes, Claudia

2012-06-01

Human exposure to arsenicals is associated with inflammatory-related diseases including different kinds of cancer as well as non-cancerous diseases like neuro-degenerative diseases, atherosclerosis, hypertension, and diabetes. Interindividual susceptibility has been mainly addressed by evaluating the role of genetic polymorphism in metabolic enzymes in inorganic arsenic (iAs) metabolism. Glutathione S-transferase omega 1-1 (GSTO1-1), which had been associated with iAs metabolism, is also known to participate in inflammatory and apoptotic cellular responses. The polymorphism A140D of GSTO1-1 has been not only associated with distinct urinary profile of arsenic metabolites in populations chronically exposed to iAs in drinking water, but also with higher risk of childhood leukemia and lung disease in non-exposed populations, suggesting that GSTO1-1 involvement in other physiologic processes different from toxics metabolism could be more relevant than is thought. We evaluated the association of the presence of A140D and E208K polymorphisms of GSTO1-1 gene with the expression of genes codifying for proteins involved in the inflammatory and apoptotic response in a human population chronically exposed to iAs through drinking water. A140D polymorphism was associated with higher expression of genes codifying for IL-8 and Apaf-1 mainly in heterozygous individuals, while E208K was associated with higher expression of IL-8 and TGF- gene, in both cases, the association was independently of iAs exposure level; however, the exposure to iAs increased slightly but significantly the influence of A140D and E208K polymorphisms on such genes expression. These results suggest an important role of GSTO1-1 in the inflammatory response and the apoptotic process and indicate that A140D and E208K polymorphisms could increase the risk of developing inflammatory and apoptosis-related diseases in As-exposed populations.

Toxic effects of arsenic on semen and hormonal profile and their amelioration with vitamin E in Teddy goat bucks.

PubMed

Zubair, M; Ahmad, M; Jamil, H; Deeba, F

2016-12-01

The present environmental study has been planned to investigate the toxic effects of arsenic on reproductive functions of Teddy bucks as well as to examine whether these toxic effects are ameliorated by vitamin E. Sixteen adult Teddy bucks were divided randomly into four equal groups A, B, C and D with following treatment: A (control), B (sodium arsenite 5 mg kg -1 BW day -1 ), C (vit E 200 mg kg -1 BW day -1  + Arsenic 5 mg kg -1 BW day -1 ) and D (vit E 200 mg kg -1 BW day -1 ). This treatment was continued for 84 days. Semen quality parameters were evaluated weekly. Male testosterone, luteinising hormone (LH), follicle-stimulating hormone (FSH) and cortisol levels were measured through enzyme-linked immunosorbent assay (ELISA) after every 2 weeks. The data were subjected to two-way analysis of variance followed by Duncan test for multiple comparisons. Semen evaluation parameters were reduced significantly (P < 0.05) in arsenic-treated animals. The serum hormonal profile of testosterone, LH and FSH was reduced significantly (P < 0.05) in arsenic group, while the serum level of cortisol was increased. Vitamin E alleviated the toxic effects of arsenic on semen and hormonal parameters. It may be concluded from this study that sodium arsenite causes major toxicity changes in semen and hormonal profile in Teddy goat bucks and vitamin E has ameliorative effects on these toxic changes. © 2016 Blackwell Verlag GmbH.

Arsenic Speciation of Terrestrial Invertebrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moriarty, M.M.; Koch, I.; Gordon, R.A.

2009-07-01

The distribution and chemical form (speciation) of arsenic in terrestrial food chains determines both the amount of arsenic available to higher organisms, and the toxicity of this metalloid in affected ecosystems. Invertebrates are part of complex terrestrial food webs. This paper provides arsenic concentrations and arsenic speciation profiles for eight orders of terrestrial invertebrates collected at three historical gold mine sites and one background site in Nova Scotia, Canada. Total arsenic concentrations, determined by inductively coupled plasma mass spectrometry (ICP-MS), were dependent upon the classification of invertebrate. Arsenic species were determined by high-performance liquid chromatography (HPLC) ICP-MS and X-ray absorptionmore » spectroscopy (XAS). Invertebrates were found by HPLC ICP-MS to contain predominantly arsenite and arsenate in methanol/water extracts, while XAS revealed that most arsenic is bound to sulfur in vivo. Examination of the spatial distribution of arsenic within an ant tissue highlighted the differences between exogenous and endogenous arsenic, as well as the extent to which arsenic is transformed upon ingestion. Similar arsenic speciation patterns for invertebrate groups were observed across sites. Trace amounts of arsenobetaine and arsenocholine were identified in slugs, ants, and spiders.« less

Methylation of inorganic arsenic in different mammalian species and population groups.

PubMed

Vahter, M

1999-01-01

Thousands of people in different parts of the world are exposed to arsenic via drinking water or contaminated soil or food. The high general toxic of arsenic has been known for centuries, and research during the last decades has shown that arsenic is a potent human carcinogen. However, most experimental cancer studies have failed to demonstrate carcinogenicity in experimental animals, indicating marked variation in sensitivity towards arsenic toxicity between species. It has also been suggested that there is a variation in susceptibility among human individuals. One reason for such variability in toxic response may be variation in metabolism. Inorganic arsenic is methylated in humans as well as animals and micro-organisms, but there are considerable differences between species and individuals. In many, but not all, mammalian species, inorganic arsenic is methylated to methylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are more rapidly excreted in urine than is the inorganic arsenic, especially the trivalent form (AsIII, arsenite) which is highly reactive with tissue components. Absorbed arsenate (AsV) is reduced to trivalent arsenic (AsIII) before the methyl groups are attached. It has been estimated that as much as 50-70% of absorbed AsV is rapidly reduced to AsIII, a reaction which seems to be common for most species. In most experimental animal species, DMA is the main metabolite excreted in urine. Compared to human subjects, very little MMA is produced. However, the rate of methylation varies considerably between species, and several species, e.g. the marmoset monkey and the chimpanzee have been shown not to methylate inorganic arsenic at all. In addition, the marmoset monkey accumulates arsenic in the liver. The rat, on the other hand, has an efficient methylation of arsenic but the formed DMA is to a large extent accumulated in the red blood cells. As a result, the rat shows a low rate of excretion of arsenic. In both human subjects and rodents exposed to DMA, about 5% of the dose is excreted in the urine as trimethylarsine oxide. It is obvious from studies on human volunteers exposed to specified doses of inorganic arsenic that the rate of excretion increases with the methylation efficiency, and there are large inter-individual variations in the methylation of arsenic. Recent studies on people exposed to arsenic via drinking water in northern Argentina have shown unusually low urinary excretion of MMA. Furthermore, children had a lower degree of methylation of arsenic than adults. Some studies indicate a lower degree of arsenic methylation in men than in women, especially during pregnancy. Whether the observed differences in methylation of arsenic are associated with variations in the susceptibility of arsenic remains to be investigated.

TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC AND ITS METHYLATED METABOLITES IN C57BL/6 MICE FOLLOWING SUBCHRONIC EXPOSURE TO ARSENATE (ASV) IN DRINKING WATER

EPA Science Inventory

The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for AsV because its trivalent metabolites hav...

Tissue Distribution And Urinary Excretion Of Inorganic Arsenic And Its Methylated Metabolites In C57BL6 Mice Following Subchronic Exposure To Arsenate In Drinking Water

EPA Science Inventory

The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for As^V because its trivalent meta...

Tissue Distribution and Urinary Excretion of Dimethylated Arsenic and Its Metabolites in Dimethylarsinic acid- or Arsenate-treated Rats - MCEARD

EPA Science Inventory

Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethy...

APPLICATION OF SAMPLE PRE-OXIDATION OF ARSENITE IN HUMAN URINE PRIOR TO SPECIATON VIA ON-LINE PHOTO-OXIDATION WITH MEMBRANE HYDRIDE GENRATION AND ICP-MS DETECTION

EPA Science Inventory

A pre-oxidation procedure which converts arsenite (AS(III)) to arsenate (As(VVV)) was investigated in urinary arsenic speciation prior to on-line photo-oxidation hydride-generation with ICP-MS detection. This sample pre-oxidation method eliminates As(III) and As(V) preservation c...

Urinary protein excretion profile: A contribution for subclinical renal damage identification among environmental heavy metals exposure in Southeast Brazil

NASA Astrophysics Data System (ADS)

Garlipp, C. R.; Bottini, P. V.; de Capitan, E. M.; Pinho, M. C.; Panzan, A. D. N.; Sakuma, A. M. A.; Paoliello, M. B.

2003-05-01

In Southeast Brazil. Ribeira Valley region has been a major public health concern due to he environmental heavy metals contamination indexes of vegetation, rocks and aquifers, caused by locai mining in the past. Human contamination low levels of heavy rnetals doesn't cause acute intoxication but ni chronic exposure, renal damage may occur with progressive tubuJointerstitial changes evolvil1g to glomemlar 1esiol1, ln this stndy we invesligated the relationship between thc profile of utillan, excreted proteins (glomerular or lubular origin) of arsenic and mercury and blood lead concentration in chiJdren and adults from highly e) qJosed regions of the Ribeira Valley. The subjects were classieed as GROUP 1 (GI; higher environmental risk n=333) and GROUP 2 (G2; lower risk of contamination. n=104). In order to determine the urinary excretion of total protein, albumin (MA, glomerular marker) and alpha i microglobulin (AIM, tubular marker) and the blood lead concentrations. random wine and blood samples were obtaiiied. Plasmatic lead levels were assessed by atomic absorption spectrometty with graphite fumace. Totai protein concentration (PROT) was assessed on a biochemical analyzer ,progallol red method). MA and AIM were determined by nephelometric method. Croup 1 showcd a higher frequency of altered urinary excretion of PROT (GI=3.4%; G2=1.0%), MA (Gl=9.0%; G2=5.1%) and AIM (Gt=7.5%, G2=3.8%), without significant differences between both groups. Elevated arscnic levels were more prevaient among subjects from Group 1 (2.8.8%) and demonstrated a significant corrolation with abiiormal iirinarv excretion of ilbumin and alpha-l-micrglobulin (p=0.019).Leadaand mercury levels showed no difference among the groups and no correlation will MAa and/or M. Oti-c dala suggests that abnormal itrinary protein excretion is relatively frequent in this population independently of the plasmatic or urinaryl heavy metal levels. The early detection of possible renal damage become necessary for effective measures can be taken to prevent clinical nephropathies.

Dose-Response Relationship between Inorganic Arsenic Exposure and Lung Cancer among Arseniasis Residents with Low Methylation Capacity.

PubMed

Hsu, Kuang-Hung; Tsui, Ke-Hung; Hsu, Ling-I; Chiou, Hung-Yi; Chen, Chien-Jen

2017-05-01

Background: Exposure to inorganic arsenic (InAs) has been documented as a risk factor for lung cancer. This study examined the association between InAs exposure, its metabolism, and lung cancer occurrence. Methods: We followed 1,300 residents from an arseniasis area in Taiwan, determined urinary InAs metabolites, and identified 39 lung cancer cases. Cox proportional hazards model was performed. Results: The results demonstrated that participants with either the primary methylation index [monomethylarsonic acid (MMA)/InAs] or the secondary methylation index [dimethylarsenic acid (DMA)/MMA] lower than their respective median values were at a higher risk of lung cancer (HRs from 3.41 to 4.66) than those with high methylation capacity. The incidence density of lung cancer increased from 79.9/100,000 (year -1 ) to 467.4/100,000 (year -1 ) for residents with low methylation capacity and from 0 to 158.5/100,000 (year -1 ) for residents with high methylation capacity when the arsenic exposure dose increased from 2 to 10 ppb to ≥200 ppb, respectively. The analyses revealed a dose-response relationship between lung cancer occurrence and increasing arsenic concentrations in drinking water as well as cumulative arsenic exposure (monotonic trend test; P < 0.05 and P < 0.05, respectively) among the residents with low methylation capacity. The relationship between arsenic exposure and lung cancer among high methylators was not statistically significant. Conclusions: Hypomethylation responses to InAs exposure may dose dependently increase lung cancer occurrence. Impact: The high-risk characteristics observed among those exposed should be considered in future preventive medicine and research on arsenic carcinogenesis. Cancer Epidemiol Biomarkers Prev; 26(5); 756-61. ©2016 AACR . ©2016 American Association for Cancer Research.

Global Gene Expression Profiling of Hyperkeratotic Skin Lesions from Inner Mongolians Chronically Exposed to Arsenic

EPA Science Inventory

The skin is an organ that is highly sensitive to chronic arsenic exposure. Skin lesions such as hyperkeratoses (HKs), which are characterized by hyperproliferation and aberrations in terminal epidermal differentiation, are common early manifestations of arsenicosis in humans. H...

Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

PubMed Central

Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

2012-01-01

Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a six month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. PMID:22521957

Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.

PubMed

Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin

2016-11-01

Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Glutathione-S-transferase-omega [MMA(V) reductase] knockout mice: Enzyme and arsenic species concentrations in tissues after arsenate administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chowdhury, Uttam K.; Zakharyan, Robert A.; Hernandez, Alba

Inorganic arsenic is a human carcinogen to which millions of people are exposed via their naturally contaminated drinking water. Its molecular mechanisms of carcinogenicity have remained an enigma, perhaps because arsenate is biochemically transformed to at least five other arsenic-containing metabolites. In the biotransformation of inorganic arsenic, GSTO1 catalyzes the reduction of arsenate, MMA(V), and DMA(V) to the more toxic + 3 arsenic species. MMA(V) reductase and human (hGSTO1-1) are identical proteins. The hypothesis that GST-Omega knockout mice biotransformed inorganic arsenic differently than wild-type mice has been tested. The livers of male knockout (KO) mice, in which 222 bp ofmore » Exon 3 of the GSTO1 gene were eliminated, were analyzed by PCR for mRNA. The level of transcripts of the GSTO1 gene in KO mice was 3.3-fold less than in DBA/1lacJ wild-type (WT) mice. The GSTO2 transcripts were about two-fold less in the KO mouse. When KO and WT mice were injected intramuscularly with Na arsenate (4.16 mg As/kg body weight); tissues removed at 0.5, 1, 2, 4, 8, and 12 h after arsenate injection; and the arsenic species measured by HPLC-ICP-MS, the results indicated that the highest concentration of the recently discovered and very toxic MMA(III), a key biotransformant, was in the kidneys of both KO and WT mice. The highest concentration of DMA(III) was in the urinary bladder tissue for both the KO and WT mice. The MMA(V) reducing activity of the liver cytosol of KO mice was only 20% of that found in wild-type mice. There appears to be another enzyme(s) other than GST-O able to reduce arsenic(V) species but to a lesser extent. This and other studies suggest that each step of the biotransformation of inorganic arsenic has an alternative enzyme to biotransform the arsenic substrate.« less

Urine biomarkers informative of human kidney allograft rejection and tolerance.

PubMed

Nissaisorakarn, Voravech; Lee, John Richard; Lubetzky, Michelle; Suthanthiran, Manikkam

2018-05-01

We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report. Copyright © 2018. Published by Elsevier Inc.

Environmental Exposure to Arsenic, Lead, and Cadmium in People Living near Janghang Copper Smelter in Korea.

PubMed

Kim, Yong-Dae; Eom, Sang-Yong; Yim, Dong-Hyuk; Kim, In-Soo; Won, Hee-Kwan; Park, Choong-Hee; Kim, Guen-Bae; Yu, Seung-Do; Choi, Byung-Sun; Park, Jung-Duck; Kim, Heon

2016-04-01

Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure.

Environmental exposure to human carcinogens in teenagers and the association with DNA damage.

PubMed

Franken, Carmen; Koppen, Gudrun; Lambrechts, Nathalie; Govarts, Eva; Bruckers, Liesbeth; Den Hond, Elly; Loots, Ilse; Nelen, Vera; Sioen, Isabelle; Nawrot, Tim S; Baeyens, Willy; Van Larebeke, Nicolas; Boonen, Francis; Ooms, Daniëlla; Wevers, Mai; Jacobs, Griet; Covaci, Adrian; Schettgen, Thomas; Schoeters, Greet

2017-01-01

We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Six hundred 14-15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel and t,t-muconic acid were inversely associated with the alkaline comet assay. This cross-sectional study found associations between current environmental exposure to (potential) human carcinogens in 14-15-year-old Flemish adolescents and short-term (oxidative) damage to DNA. Prospective follow-up will be required to investigate whether long-term effects may occur due to complex environmental exposures. Copyright © 2016 Elsevier Inc. All rights reserved.

Provision of well-water treatment units to 600 households in Bangladesh: A longitudinal analysis of urinary arsenic indicates fading utility.

PubMed

Sanchez, Tiffany R; Levy, Diane; Shahriar, Mohammad Hasan; Uddin, Mohammad Nasir; Siddique, Abu B; Graziano, Joseph H; Lomax-Luu, Angela; van Geen, Alexander; Gamble, Mary V

2016-09-01

Millions of villagers in Bangladesh remain exposed to high levels of arsenic (As) from drinking untreated well-water even though the scale of the problem was recognized 15years ago. Water treatment at the household-level has been promoted as a viable complement but few longitudinal studies of their efficacy using an objective measure of exposure have been conducted. Participants (N=622) of a nutrition trial in Araihazar, Bangladesh were each provided with READ-F filters at the beginning of the study and encouraged to use them over the 6month duration of the intervention. Well-water As, treated water As, and urinary As were monitored periodically during the trial and measured again one year after the trial ended. The READ-F filters were initially well received and median urinary As levels for participants declined from 117μg/L to 51μg/L within a single week. However, median urinary As levels gradually rose back to 126μg/L by the end of the trial. Fifty filters were replaced over the course of the trial because of insufficient As removal or reduced flow. With these exceptions, most of the treated water met the WHO guideline for As in drinking water of 10μg/L. One year after the nutritional trial ended, 95% of participants had abandoned their filter citing inconvenience as the primary reason. At that time, median urinary As levels for 10 participants who had switched to a nearby low-As well had declined to 63μg/L. Participants were probably no longer using the READ-F filter long before the 6month nutritional intervention ended despite claiming that they were using them. Household-level treatment is likely to continue to play a minor role in the effort to reduce As exposure in Bangladesh. Understanding the limitations of such expensive interventions is important for future policy regarding As mitigation. Copyright © 2016 Elsevier B.V. All rights reserved.

Exposure to arsenic and lead of children living near a copper-smelter in San Luis Potosi, Mexico: Importance of soil contamination for exposure of children.

PubMed

Carrizales, Leticia; Razo, Israel; Téllez-Hernández, Jesús I; Torres-Nerio, Rocío; Torres, Arturo; Batres, Lilia E; Cubillas, Ana-Cristina; Díaz-Barriga, Fernando

2006-05-01

The objective of this study was to assess the levels of soil contamination and child exposure in areas next to a primary smelter (arsenic-copper metallurgical) located in the community of Morales in San Luis Potosi, Mexico. In Morales, 90% of the soil samples studied in this work were above 400 mg/kg of lead, and above 100 mg/kg of arsenic, which are guidelines recommended by the United States Environmental Protection Agency (EPA). Bioaccessibility of these metals was studied in vitro in 10 soil samples; the median values of bioaccessibility obtained in these samples were 46.5% and 32.5% for arsenic and lead. Since the concentrations of arsenic and lead in soil were above normal values, and taking into account the bioaccessibility results, exposure to these metals was evaluated in children. Regarding lead, children aged 3-6 years had the highest mean blood lead levels; furthermore, 90% of them had concentrations above 10 microg/dl (CDC's action level). Total urinary arsenic was higher in children aged 8-9 yr; however, the percentage of children with concentrations above 50 microg/g creatinine (CDC's action level) or 100 microg/g creatinine (World Health Organization [WHO] action level) was similar among different age groups. Using the EPAs integrated exposure uptake biokinetic model for lead in children (IEUBK), we estimated that 87% of the total lead in blood is obtained from the soil/dust pathway. The exposure dose to arsenic, estimated for the children living in Morales using Monte Carlo analysis and the arsenic concentrations found in soil, was above the EPA's reference dose. With all these results, it is evident that studies are needed in order to identify adverse health effects in children living in Morales; nevertheless, it is more important to develop a risk reduction program as soon as possible.

Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan.

PubMed

Hsieh, Ru-Lan; Su, Chien-Tien; Shiue, Horng-Sheng; Chen, Wei-Jen; Huang, Shiau-Rung; Lin, Ying-Chin; Lin, Ming-I; Mu, Shu-Chi; Chen, Ray-Jade; Hsueh, Yu-Mei

2017-04-15

Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (As III ), arsenate (As V ), monomethylarsonic acid (MMA V ), and dimethylarsinic acid (DMA V ) were measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G+G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08-2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity. Copyright © 2017 Elsevier Inc. All rights reserved.

Proteomic Profiling of Bladders from Mice Exposed with Sodium Arsenite

EPA Science Inventory

Arsenic, an environmental contaminant, has been linked with cancer of the bladder in humans. To study the mode of action of arsenic, female CH3 mice were exposed to 85 ppm sodium arsenite in their drinking water for 30 days. Following the exposure a comparative proteomic analysis...

EXPRESSION OF AS3MT ALTERS TRANSCRIPTIONAL PROFILES IN HUMAN UROTHELIAL CELLS EXPOSED TO ARSENITE

EPA Science Inventory

Inorganic arsenic (iAs) is an environmental toxin and human carcinogen. The enzymatic methylation of iAs that is catalyzed by arsenic (+3 oxidation state)-methyltransferase (AS3MT) generates reactive methylated intermediates that contribute to the toxic and carcinogenic effects ...

Urinary tuberculosis is associated with the development of urothelial carcinoma but not renal cell carcinoma: a nationwide cohort study in Taiwan

PubMed Central

Lien, Y-C; Wang, J-Y; Lee, M-C; Shu, C-C; Chen, H-Y; Hsieh, C-H; Lee, C-H; Lee, L-N; Chao, K-M

2013-01-01

Background: Obstructive uropathy and chronic urinary tract infection increase the risk of urinary tract cancer. Urinary tuberculosis (UTB) can cause chronic urinary tract inflammation, lead to obstructive uropathy, and potentially contribute to the development of urinary tract cancer. However, the association between UTB and urinary tract cancer has not been studied. Methods: This study enrolled 135 142 tuberculosis (TB) cases (male, 69%) from a nationwide health insurance research database in Taiwan and investigated the risk factors for urinary tract cancer, with emphasis on a history of UTB. The incidence of urinary tract cancer in the general population without TB was also calculated for comparison. Results: The TB patients had a mean age of 57.5±19.5 years. Of the 1287 UTB and 133 855 non-UTB patients, 15 (1.2%) and 396 (0.3%) developed urothelial carcinoma, respectively (P<0.001); and 2 (0.2%) and 96 (0.1%) developed renal cell carcinoma, respectively (P=0.240). Cox regression analysis revealed that age, male sex, end-stage renal disease, obstructive uropathy, arsenic intoxication, organ transplantation, and UTB (hazard ratio: 3.38 (2.01–5.69)) were independent risk factors for urothelial carcinoma. The hazard ratio of UTB was higher among female patients (5.26 (2.12–13.06)) than that among male patients (2.96 (1.57–5.60)). Conclusion: Urinary tuberculosis had a strong association with urothelial carcinoma, but not with renal cell carcinoma. In TB endemic areas, the urinary tract of TB patients should be scrutinised. It is also imperative that these patients be followed-up carefully in the post-treatment period, and urinalysis, ultrasonography or endoscopy should be an integral part of the follow-up. PMID:24129236

Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast.

PubMed

Guo, Lan; Ganguly, Abantika; Sun, Lingling; Suo, Fang; Du, Li-Lin; Russell, Paul

2016-10-13

Heavy metals and metalloids such as cadmium [Cd(II)] and arsenic [As(III)] are widespread environmental toxicants responsible for multiple adverse health effects in humans. However, the molecular mechanisms underlying metal-induced cytotoxicity and carcinogenesis, as well as the detoxification and tolerance pathways, are incompletely understood. Here, we use global fitness profiling by barcode sequencing to quantitatively survey the Schizosaccharomyces pombe haploid deletome for genes that confer tolerance of cadmium or arsenic. We identified 106 genes required for cadmium resistance and 110 genes required for arsenic resistance, with a highly significant overlap of 36 genes. A subset of these 36 genes account for almost all proteins required for incorporating sulfur into the cysteine-rich glutathione and phytochelatin peptides that chelate cadmium and arsenic. A requirement for Mms19 is explained by its role in directing iron-sulfur cluster assembly into sulfite reductase as opposed to promoting DNA repair, as DNA damage response genes were not enriched among those required for cadmium or arsenic tolerance. Ubiquinone, siroheme, and pyridoxal 5'-phosphate biosynthesis were also identified as critical for Cd/As tolerance. Arsenic-specific pathways included prefoldin-mediated assembly of unfolded proteins and protein targeting to the peroxisome, whereas cadmium-specific pathways included plasma membrane and vacuolar transporters, as well as Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional coactivator that controls expression of key genes required for cadmium tolerance. Notable differences are apparent with corresponding screens in the budding yeast Saccharomyces cerevisiae, underscoring the utility of analyzing toxic metal defense mechanisms in both organisms. Copyright © 2016 Guo et al.

Selective Sensitization of Zinc Finger Protein Oxidation by Reactive Oxygen Species through Arsenic Binding*

PubMed Central

Zhou, Xixi; Cooper, Karen L.; Sun, Xi; Liu, Ke J.; Hudson, Laurie G.

2015-01-01

Cysteine oxidation induced by reactive oxygen species (ROS) on redox-sensitive targets such as zinc finger proteins plays a critical role in redox signaling and subsequent biological outcomes. We found that arsenic exposure led to oxidation of certain zinc finger proteins based on arsenic interaction with zinc finger motifs. Analysis of zinc finger proteins isolated from arsenic-exposed cells and zinc finger peptides by mass spectrometry demonstrated preferential oxidation of C3H1 and C4 zinc finger configurations. C2H2 zinc finger proteins that do not bind arsenic were not oxidized by arsenic-generated ROS in the cellular environment. The findings suggest that selectivity in arsenic binding to zinc fingers with three or more cysteines defines the target proteins for oxidation by ROS. This represents a novel mechanism of selective protein oxidation and demonstrates how an environmental factor may sensitize certain target proteins for oxidation, thus altering the oxidation profile and redox regulation. PMID:26063799

A retrospective review of the dermatologic manifestations of chronic arsenic poisoning in the Philippines.

PubMed

Sy, Sheena Maureen T; Salud-Gnilo, Charissa M; Yap-Silva, Claudine; Tababa, Erin Jane L

2017-07-01

The Section of Dermatology of the University of the Philippines, Philippine General Hospital, reported a case of chronic arsenic poisoning from a community in Luzon island to the Department of Health resulting in the conduct of two health and environmental assessment missions in December 2014. To describe the demographic profile and cutaneous manifestations of chronic arsenic poisoning among affected residents in Luzon, Philippines. A review of the medical records of 116 residents screened during the health assessment missions in December 2014 was conducted. Among the 116 residents screened, 81 (70%) had clinically confirmed arsenic keratoses and hyperpigmentation. Among them, 52 were males and 29 were females with age range of 4-82 years. Two cases of squamous cell carcinoma in situ were detected through skin biopsy. High levels of arsenic in the tap water and topsoil supported the occurrence of an epidemic of chronic arsenic poisoning. Specific dermatologic findings of arsenic keratoses and pigmentation were common among the residents screened. Significantly higher occurrence of arsenic keratoses was seen in adults. © 2017 The International Society of Dermatology.

Magnesium, zinc, arsenic, selenium and platinum urinary excretion from cancer patients of Antofagasta region, Chile: multi-metal approach

PubMed Central

Pizarro, I; Rivera, L; Ávila, J; Cortés, P

2016-01-01

Objectives To evaluate the short-term 24 h urinary excretion of platinum, arsenic, selenium, magnesium and zinc in patients with lung cancer and with cancer other than lungs treated with cisplatin or/and carboplatin from Antofagasta, Chile. Design Urine measurements of Pt and Se were made by inductively coupled plasma optical emission spectrometry, As by hydride-generation atomic absorption spectrometry and Mg and Zn by means of flame furnace atomic absorption spectrometry. Setting All samples were provided by the Oncological Centre of Antofagasta Regional Hospital (Region of Antofagasta, Chile). Participants Ninety 24-h urine samples from cancer patients after the infusion of Pt-base drugs and 10 24-h urine samples from cancer patients not treated with metal-base drugs. Main outcome measures Concentrations of Pt, Se, As, Zn and Mg coming from 24-h urine samples. Results Pt excreted was not significantly different between patients with lung and other cancers treated with cisplatin. The excretion of Mg, Zn and Se was greater than As. Then, Pt favours the excretion of essential elements. For lung and other types of cancers treated with drugs without Pt, excretion of Mg, Zn and Se was also greater than that of As, suggesting antagonism Mg-Zn-Se–anti-cancer drug relationship. Conclusions The amounts of Mg, Zn and Se excreted were greater than for As either with or without Pt-containing drugs, suggesting antagonist Mg-Zn-Se–anti-cancer drug relationships. The excretion of As, Mg, Zn and Se is induced by Pt. Knowledge obtained can contribute to understanding the arsenic cancer mechanism and the As-Mg-Zn-Se-Pt inter-element association for lung cancer and other types of cancer. PMID:27757244

Inorganic Arsenic and Basal Cell Carcinoma in Areas of Hungary, Romania, and Slovakia: A Case–Control Study

PubMed Central

Leonardi, Giovanni; Vahter, Marie; Clemens, Felicity; Goessler, Walter; Gurzau, Eugen; Hemminki, Kari; Hough, Rupert; Koppova, Kvetoslava; Kumar, Rajiv; Rudnai, Peter; Surdu, Simona

2012-01-01

Background: Inorganic arsenic (iAs) is a potent carcinogen, but there is a lack of information about cancer risk for concentrations < 100 μg/L in drinking water. Objectives: We aimed to quantify skin cancer relative risks in relation to iAs exposure < 100 μg/L and the modifying effects of iAs metabolism. Methods: The Arsenic Health Risk Assessment and Molecular Epidemiology (ASHRAM) study, a case–control study, was conducted in areas of Hungary, Romania, and Slovakia with reported presence of iAs in groundwater. Consecutively diagnosed cases of basal cell carcinoma (BCC) of the skin were histologically confirmed; controls were general surgery, orthopedic, and trauma patients who were frequency matched to cases by age, sex, and area of residence. Exposure indices were constructed based on information on iAs intake over the lifetime of participants. iAs metabolism status was classified based on urinary concentrations of methylarsonic acid (MA) and dimethylarsinic acid (DMA). Associations were estimated by multivariable logistic regression. Results: A total of 529 cases with BCC and 540 controls were recruited for the study. BCC was positively associated with three indices of iAs exposure: peak daily iAs dose rate, cumulative iAs dose, and lifetime average water iAs concentration. The adjusted odds ratio per 10-μg/L increase in average lifetime water iAs concentration was 1.18 (95% confidence interval: 1.08, 1.28). The estimated effect of iAs on cancer was stronger in participants with urinary markers indicating incomplete metabolism of iAs: higher percentage of MA in urine or a lower percentage of DMA. Conclusion: We found a positive association between BCC and exposure to iAs through drinking water with concentrations < 100 μg/L. PMID:22436128

Arsenic induced toxicity in broiler chicks and its alleviation with ascorbic acid: a toxico-patho-biochemical study

USGS Publications Warehouse

Khan, Ahrar; Sharaf, Rabia; Khan, Muhammad Zargham; Saleemi, Muhammad Kashif; Mahmood, Fazal

2013-01-01

To find out toxico-pathological effects of arsenic (As) and ameliorating effect of ascorbic acid (Vit C), broilers birds were administered 50 and 250 mg/kg arsenic and Vit C, respectively alone/in combination. As-treated birds exhibited severe signs of toxicity such as dullness, depression, increased thirst, open mouth breathing and watery diarrhea. All these signs were partially ameliorated with the treatment of Vit C. As-treated birds showed a significant decrease in serum total proteins while serum enzymes, urea and creatinine were significantly increased. Alkaline phosphatase and lactate dehydrogenase completely whereas proteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were partial ameliorated in birds treated with As+Vit C as compared to As-treated and control birds. Pale and hemorrhagic liver and swollen kidneys were observed in As-treated birds. Histopathologically, liver exhibited congestion and cytoplasmic vacuolation while in kidneys, condensation of tubular epithelium nuclei, epithelial necrosis, increased urinary spaces, sloughing of tubules from basement membrane and cast deposition were observed in As-treated birds. Pathological lesions were partially ameliorated with the treatment of Vit C. It can be concluded that arsenic induces biochemical and histopathological alterations in broiler birds; however, these toxic effects can be partially attenuated by Vit C.

Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence.

PubMed

Saint-Jacques, Nathalie; Parker, Louise; Brown, Patrick; Dummer, Trevor Jb

2014-06-02

Arsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework. Forty studies met the selection criteria. Seventeen provided point estimates of arsenic concentrations in drinking water and were used in a meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies) and kidney cancer mortality (2 studies). Risk estimates for incidence and mortality were analyzed separately using Generalized Linear Models. Predicted risks for bladder cancer incidence were estimated at 10, 50 and 150 μg/L arsenic in drinking water. Bootstrap randomizations were used to assess robustness of effect size. Twenty-eight studies observed an association between arsenic in drinking water and bladder cancer. Ten studies showed an association with kidney cancer, although of lower magnitude than that for bladder cancer. The meta-analyses showed the predicted risks for bladder cancer incidence were 2.7 [1.2-4.1]; 4.2 [2.1-6.3] and; 5.8 [2.9-8.7] for drinking water arsenic levels of 10, 50, and 150 μg/L, respectively. Bootstrapped randomizations confirmed this increased risk, but, lowering the effect size to 1.4 [0.35-4.0], 2.3 [0.59-6.4], and 3.1 [0.80-8.9]. The latter suggests that with exposures to 50 μg/L, there was an 83% probability for elevated incidence of bladder cancer; and a 74% probability for elevated mortality. For both bladder and kidney cancers, mortality rates at 150 ug/L were about 30% greater than those at 10 μg/L. Arsenic in drinking water is associated with an increased risk of bladder and kidney cancers, although at lower levels (<150 μg/L), there is uncertainty due to the increased likelihood of exposure misclassification at the lower end of the exposure curve. Meta-analyses suggest exposure to 10 μg/L of arsenic in drinking water may double the risk of bladder cancer, or at the very least, increase it by about 40%. With the large number of people exposed to these arsenic concentrations worldwide the public health consequences of arsenic in drinking water are substantial.

Associations between Blood and Urine Arsenic Concentrations and Global Levels of Post-Translational Histone Modifications in Bangladeshi Men and Women

PubMed Central

Howe, Caitlin G.; Liu, Xinhua; Hall, Megan N.; Slavkovich, Vesna; Ilievski, Vesna; Parvez, Faruque; Siddique, Abu B.; Shahriar, Hasan; Uddin, Mohammad N.; Islam, Tariqul; Graziano, Joseph H.; Costa, Max; Gamble, Mary V.

2016-01-01

Background: Exposure to inorganic arsenic is associated with numerous adverse health outcomes, with susceptibility differing by sex. Although evidence from in vitro studies suggests that arsenic alters post-translational histone modifications (PTHMs), evidence in humans is limited. Objectives: The objectives were to determine: a) if arsenic exposure is associated with global (percent) levels of PTHMs H3K36me2, H3K36me3, and H3K79me2 in a sex-dependent manner, and b) if %PTHMs are stable when arsenic exposure is reduced. Methods: We examined associations between arsenic, measured in blood and urine, and %PTHMs in peripheral blood mononuclear cells from 317 participants enrolled in the Bangladesh Folic Acid and Creatine Trial (FACT). We also examined the stability of %PTHMs after the use of arsenic-removal water filters (n = 60). Results: Associations between natural log–transformed (ln) urinary arsenic, adjusted for creatinine (uAsCr), and %H3K36me2 differed significantly between men and women (p = 0.01). ln(uAsCr) was positively associated with %H3K36me2 in men [β = 0.12; 95% confidence interval (CI): 0.01, 0.23, p = 0.03] but was negatively associated with %H3K36me2 in women (β = –0.05; 95% CI: –0.12, 0.02, p = 0.19). The patterns of associations with blood arsenic were similar. On average, water filter use was also associated with reductions in %H3K36me2 (p < 0.01), but this did not differ significantly by sex. Arsenic was not significantly associated with %H3K36me3 or %H3K79me2 in men or women. Conclusions: Arsenic exposure was associated with %H3K36me2 in a sex-specific manner but was not associated with %H3K36me3 or %H3K79me2. Additional studies are needed to assess changes in %H3K36me2 after arsenic removal. Citation: Howe CG, Liu X, Hall MN, Slavkovich V, Ilievski V, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Costa M, Gamble MV. 2016. Associations between blood and urine arsenic concentrations and global levels of post-translational histone modifications in Bangladeshi men and women. Environ Health Perspect 124:1234–1240; http://dx.doi.org/10.1289/ehp.1510412 PMID:26967670

Major urinary protein (MUP) profiles show dynamic changes rather than individual ‘barcode’ signatures

PubMed Central

Thoß, M.; Luzynski, K.C.; Ante, M.; Miller, I.; Penn, D.J.

2016-01-01

House mice (Mus musculus) produce a variable number of major urinary proteins (MUPs), and studies suggest that each individual produces a unique MUP profile that provides a distinctive odor signature controlling individual and kin recognition. This ‘barcode hypothesis’ requires that MUP urinary profiles show high individual variability within populations and also high individual consistency over time, but tests of these assumptions are lacking. We analyzed urinary MUP profiles of 66 wild-caught house mice from eight populations using isoelectric focusing. We found that MUP profiles of wild male house mice are not individually unique, and though they were highly variable, closer inspection revealed that the variation strongly depended on MUP band type. The prominent (‘major) bands were surprisingly homogenous (and hence most MUPs are not polymorphic), but we also found inconspicuous (‘minor’) bands that were highly variable and therefore potential candidates for individual fingerprints. We also examined changes in urinary MUP profiles of 58 males over time (from 6 to 24 weeks of age), and found that individual MUP profiles and MUP concentration were surprisingly dynamic, and showed significant changes after puberty and during adulthood. Contrary to what we expected, however, the minor bands were the most variable over time, thus no good candidates for individual fingerprints. Although MUP profiles do not provide individual fingerprints, we found that MUP profiles were more similar among siblings than non-kin despite considerable fluctuation. Our findings show that MUP profiles are not highly stable over time, they do not show strong individual clustering, and thus challenge the barcode hypothesis. Within-individual dynamics of MUP profiles indicate a different function of MUPs in individual recognition than previously assumed and advocate an alternative hypothesis (‘dynamic changes’ hypothesis). PMID:26973837

Major urinary protein (MUP) profiles show dynamic changes rather than individual 'barcode' signatures.

PubMed

Thoß, M; Luzynski, K C; Ante, M; Miller, I; Penn, D J

2015-06-30

House mice ( Mus musculus) produce a variable number of major urinary proteins (MUPs), and studies suggest that each individual produces a unique MUP profile that provides a distinctive odor signature controlling individual and kin recognition. This 'barcode hypothesis' requires that MUP urinary profiles show high individual variability within populations and also high individual consistency over time, but tests of these assumptions are lacking. We analyzed urinary MUP profiles of 66 wild-caught house mice from eight populations using isoelectric focusing. We found that MUP profiles of wild male house mice are not individually unique, and though they were highly variable, closer inspection revealed that the variation strongly depended on MUP band type. The prominent ('major) bands were surprisingly homogenous (and hence most MUPs are not polymorphic), but we also found inconspicuous ('minor') bands that were highly variable and therefore potential candidates for individual fingerprints. We also examined changes in urinary MUP profiles of 58 males over time (from 6 to 24 weeks of age), and found that individual MUP profiles and MUP concentration were surprisingly dynamic, and showed significant changes after puberty and during adulthood. Contrary to what we expected, however, the minor bands were the most variable over time, thus no good candidates for individual fingerprints. Although MUP profiles do not provide individual fingerprints, we found that MUP profiles were more similar among siblings than non-kin despite considerable fluctuation. Our findings show that MUP profiles are not highly stable over time, they do not show strong individual clustering, and thus challenge the barcode hypothesis. Within-individual dynamics of MUP profiles indicate a different function of MUPs in individual recognition than previously assumed and advocate an alternative hypothesis ('dynamic changes' hypothesis).

Arsenic-Based Life: An Active Learning Assignment for Teaching Scientific Discourse

ERIC Educational Resources Information Center

Johnson, R. Jeremy

2017-01-01

Among recent high profile scientific debates was the proposal that life could exist with arsenic in place of phosphorous in its nucleic acids and other biomolecules. Soon after its initial publication, scientists across diverse disciplines began to question this extraordinary claim. Using the original article, its claims, its scientific support,…

Toxicity of dimethylmonothioarsinic acid toward human epidermoid carcinoma A431 cells.

PubMed

Naranmandura, Hua; Ibata, Kenji; Suzuki, Kazuo T

2007-08-01

Chronic ingestion of arsenic-contaminated drinking water induces skin lesions and urinary bladder cancer in humans. It is now recognized that thioarsenicals such as dimethylmonothioarsinic acid (DMMTA (V)) are commonly excreted in the urine of humans and animals and that the production of DMMTA (V) may be a risk factor for the development of the diseases caused by arsenic. The toxicity of DMMTA (V) was compared with that of related nonthiolated arsenicals with respect to cell viability, uptake ability, generation of reactive oxygen species (ROS), and cell cycle progression of human epidermoid carcinoma A431 cells, arsenate (iAs (V)), arsenite (iAs (III)), dimethylarsinic acid (DMA (V)), and dimethylarsinous acid (DMA (III)) being used as reference nonthiolated arsenicals. DMMTA (V) (LC 50 = 10.7 microM) was shown to be much more cytotoxic than iAs (V) (LC 50 = 571 microM) and DMA (V) (LC 50 = 843 microM), and its potency was shown to be close to that of trivalent arsenicals iAs (III) (LC 50 = 5.49 microM) and DMA (III) (LC 50 = 2.16 microM). The greater cytotoxicity of DMMTA (V) was associated with greater cellular uptake and distribution, and the level of intracellular ROS remarkably increased in A431 cells upon exposure to DMMTA (V) compared to that after exposure to other trivalent arsenicals at the respective LC 50. Exposure of DMMTA (V) to cells for 24 h induced cell cycle perturbation. Namely, the percentage of cells residing in S and G2/M phases increased from 10.2 and 15.6% to 46.5 and 20.8%, respectively. These results suggest that although DMMTA (V) is a pentavalent arsenical, it is taken up efficiently by cells and causes various levels of toxicity, in a manner different from that of nonthiolated pentavalent arsenicals, demonstrating that DMMTA (V) is one of the most toxic arsenic metabolites. The high cytotoxicity of DMMTA (V) was explained and/or proposed by (1) efficient uptake by cells followed by (2) its transformation to DMA (V), (3) producing ROS in the redox equilibrium between DMA (V) and DMA (III) in the presence of glutathione.

Effect of the Aqueous Extract of Lantana grisebachii Stuck Against Bioaccumulated Arsenic-Induced Oxidative and Lipid Dysfunction in Rat Splenocytes.

PubMed

Ramos Elizagaray, Sabina I; Quiroga, Patricia L; Pérez, Roberto D; Sosa, Carlos; Pérez, Carlos A; Bongiovanni, Guillermina A; Soria, Elio A

2018-06-29

Arsenic (As) is a worldwide immunotoxic agent that is in contaminated waters and consumed by mammals. Phytotherapy may counteract its harmful effects. Lantana grisebachii Stuck (LG, Verbenaceae) and its extract are proposed as protective, given vvits in vitro bioactivity. The aim was to determine the protective capacity of the aqueous LG extract on splenocytes exposed in vivo to arsenic. Splenocytes were obtained from an arsenicosis model (Wistar rats consuming orally 0 [control; C] or 5 mg/Kg/d of As) that received 0-100 mg/Kg/d of LG extract for 30 days. As content (total reflection X-ray fluorescence), fatty acid profile (gas chromatography), γ-glutamyl transpeptidase activity (Szasz method), peroxides (xylenol orange-based assay), and nitrites (Griess reaction) were then assayed in viable splenocytes. Data were analyzed with ANOVA and the Tukey's test (p < .05). It was observed that the splenocytes contained 2.2 mg/Kg of this elemental arsenic. With γ-glutamyl transpeptidase inhibition and consequent triggering of hydroperoxides (p < .05), it was observed to increase saturated fatty acids and alter lipid profiles. LG treatment avoided damaging effects with values similar to unexposed C (p < .05), and cellular arsenic concentration (p < .0001). In conclusion, the aqueous extract of L. grisebachii counteracted arsenic toxicity in rat splenocytes by preventing its cellular accumulation and induction of lipid and redox disturbances, which may impair immune function.

Quantitative X-ray photoelectron spectroscopy-based depth profiling of bioleached arsenopyrite surface by Acidithiobacillus ferrooxidans

NASA Astrophysics Data System (ADS)

Zhu, Tingting; Lu, Xiancai; Liu, Huan; Li, Juan; Zhu, Xiangyu; Lu, Jianjun; Wang, Rucheng

2014-02-01

In supergene environments, microbial activities significantly enhance sulfide oxidation and result in the release of heavy metals, causing serious contamination of soils and waters. As the most commonly encountered arsenic mineral in nature, arsenopyrite (FeAsS) accounts for arsenic contaminants in various environments. In order to investigate the geochemical behavior of arsenic during microbial oxidation of arsenopyrite, (2 3 0) surfaces of arsenopyrite slices were characterized after acidic (pH 2.00) and oxidative decomposition with or without an acidophilic microorganism Acidithiobacillus ferrooxidans. The morphology as well as chemical and elemental depth profiles of the oxidized arsenopyrite surface were investigated by scanning electron microscopy and X-ray photoelectron spectroscopy. With the mediation of bacteria, cell-shaped and acicular pits were observed on the reacted arsenopyrite surface, and the concentration of released arsenic species in solution was 50 times as high as that of the abiotic reaction after 10 days reaction. Fine-scale XPS depth profiles of the reacted arsenopyrite surfaces after both microbial and abiotic oxidation provided insights into the changes in chemical states of the elements in arsenopyrite surface layers. Within the 450 nm surface layer of abiotically oxidized arsenopyrite, Fe(III)-oxides appeared and gradually increased towards the surface, and detectable sulfite and monovalent arsenic appeared above 50 nm. In comparison, higher contents of ferric sulfate, sulfite, and arsenite were found in the surface layer of approximately 3 μm of the microbially oxidized arsenopyrite. Intermediates, such as Fe(III)-AsS and S0, were detectable in the presence of bacteria. Changes of oxidative species derived from XPS depth profiles show the oxidation sequence is Fe > As = S in abiotic oxidation, and Fe > S > As in microbial oxidation. Based on these results, a possible reaction path of microbial oxidation was proposed in a concept model.

Effects of co-administration of dietary sodium arsenate and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) on the rat bladder epithelium.

PubMed

Suzuki, Shugo; Arnold, Lora L; Pennington, Karen L; Kakiuchi-Kiyota, Satoko; Chen, Baowei; Lu, Xiufen; Le, X Chris; Cohen, Samuel M

2012-09-28

Inorganic arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent, is capable of reducing pentavalent arsenicals to the trivalent state and binding to the trivalent species, and it has been used in the treatment of heavy metal poisoning in humans. Therefore, we investigated the ability of DMPS to inhibit the cytotoxicity and regenerative urothelial cell proliferation induced by arsenate administration in vivo. Female rats were treated for 4 weeks with 100 ppm As(V). DMPS (2800 ppm) co-administered in the diet significantly reduced the As(V)-induced cytotoxicity of superficial cells detected by scanning electron microscopy (SEM), and the incidence of simple hyperplasia observed by light microscopy and the bromodeoxyuridine (BrdU) labeling index. It also reduced the total concentration of arsenicals in the urine and the methylation of arsenic. There were no differences in oxidative stress as assessed by immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8OHdG) of the bladder urothelium. No differences were detected in urine sediments between groups. These data suggest that DMPS has the ability to inhibit both arsenate-induced acute toxicity and regenerative proliferation of the rat bladder epithelium, most likely by decreasing exposure of the urothelium to trivalent arsenicals excreted in the urine. These data provide additional evidence that the effects of arsenate exposure in vivo do not appear to be related to oxidative effects on dG in DNA. Copyright © 2012. Published by Elsevier Ireland Ltd.

Effect of vitamin E supplementation on arsenic induced alteration in blood biochemical profile, oxidant/antioxidant status, serum cortisol level and retention of arsenic and selenium in goats.

PubMed

Mohanta, Ranjan Kumar; Garg, Anil Kumar; Dass, Ram Sharan

2015-01-01

Arsenic (As) exerts oxidative stress with depletion of body selenium in monogastric animals. But in ruminants this fact is not yet verified. Vitamin E is an effective dietary antioxidant. Thus, in this experiment, the protective effect of vitamin E against arsenic toxicity induced by sodium arsenite (60mg As/kg diet) was investigated in goat kids. For this, 21 male kids were divided into three equal groups and fed either basal diet as such (control), or supplemented with 60mg As/kg diet and 60mg As/kg diet+250IU vitamin E/kg diet for 180 days. Vitamin E supplementation alleviated the toxic effects caused by arsenic on serum alanine aminotransferase and aspartate aminotransferase and lipid peroxidation. It also prevented the depletion of reduced glutathione content and reduction in activity of catalase, superoxide dismutase and glutathione-s-transferase in erythrocytes resulted from arsenic intoxication. The elevated levels of arsenic and reduced levels of selenium in the serum and tissues in arsenic treated animals were attenuated by vitamin E supplementation, though not completely. However, serum cortisol level was not affected by arsenic. It was concluded that arsenic exerts cortisol independent stressor mechanism and supplementation of vitamin E at a level of 250IU/kg diet was partially effective in reducing tissue accumulation of arsenic in the body and protect the kids from oxidative stress induced by arsenic. Copyright © 2014 Elsevier GmbH. All rights reserved.

Urinary Metabolite Profiles May be Predictive of Cognitive Performance Under Conditions of Acute Sleep Deprivation

DTIC Science & Technology

2016-01-01

temporal changes in urinary metabolite profiles mirrored cognitive performance during continuous wakefulness. Additionally , subjects identified by...profiles mirrored cognitive performance during continuous wakefulness. Additionally , subjects identified by cognitive assessments as having a high...field studies and would have little useful application in occupational or military operational environments. Addition - ally, their usefulness is

Maternal exposure to metals—Concentrations and predictors of exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Callan, A.C., E-mail: a.callan@ecu.edu.au; Hinwood, A.L.; Ramalingam, M.

2013-10-15

A variety of metals are important for biological function but have also been shown to impact health at elevated concentrations, whereas others have no known biological function. Pregnant women are a vulnerable population and measures to reduce exposure in this group are important. We undertook a study of maternal exposure to the metals, aluminium, arsenic, copper, cobalt, chromium, lithium, manganese, nickel, selenium, tin, uranium and zinc in 173 participants across Western Australia. Each participant provided a whole blood and urine sample, as well as drinking water, residential soil and dust samples and completed a questionnaire. In general the concentrations ofmore » metals in all samples were low with the notable exception of uranium (blood U mean 0.07 µg/L, range <0.01–0.25 µg/L; urinary U mean 0.018 µg/g creatinine, range <0.01–0.199 µg/g creatinine). Factors that influenced biological concentrations were consumption of fish which increased urinary arsenic concentrations, hobbies (including mechanics and welding) which increased blood manganese concentrations and iron/folic acid supplement use which was associated with decreased concentrations of aluminium and nickel in urine and manganese in blood. Environmental concentrations of aluminium, copper and lithium were found to influence biological concentrations, but this was not the case for other environmental metals concentrations. Further work is underway to explore the influence of diet on biological metals concentrations in more detail. The high concentrations of uranium require further investigation. -- Highlights: • High concentrations of uranium with respect to international literature. • Environmental concentrations of Al, Cu and Li influenced urinary concentrations. • Exposure to mechanics/welding hobbies increased blood Mn concentrations. • Iron/Folic acid supplements reduced biological concentrations of Al, Ni and Mn.« less

Assessment of urinary metals following exposure to a large vegetative fire, New Mexico, 2000.

PubMed

Wolfe, Mitchell I; Mott, Joshua A; Voorhees, Ronald E; Sewell, C Mack; Paschal, Dan; Wood, Charles M; McKinney, Patrick E; Redd, Stephen

2004-03-01

In May 2000, a vegetative fire burned 47,000 acres in northern New Mexico, including 7500 acres of land administered by the Los Alamos National Laboratory. We evaluated potential human exposures from the fire. We surveyed two populations (firefighters and the general population) in four cities for urine heavy metal concentrations. Reference concentrations were based on the Third National Health and Nutrition Examination Survey (NHANES III). Multivariate linear regression assessed the association of urinary metal concentrations with smoke exposure. We also performed isotopic analysis of uranium and cesium on a subset of specimens. A total of 92 firefighters and 135 nonfirefighters participated. In both populations, urinary nickel, cesium, chromium, and uranium concentrations were greater than expected compared with NHANES III reference values. No values required immediate medical follow-up. Regression analysis demonstrated that for National Guard members, arsenic and cadmium levels were significantly related to smoke exposure, and for firefighters, cesium and arsenic levels were significantly related to exposure; however, only for cesium in National Guard members was this association in the positive direction. Isotopic analysis demonstrated that the cesium and uranium were naturally occurring. Some people had spot urine metal concentrations above nationally derived reference values, and values for some metals were associated with smoke exposure. These associations had little public health or clinical importance. Studies of exposures resulting from vegetative fires are difficult, and careful consideration should be given to the technical and communication processes at the outset of a fire exposure investigation. Recommendations for future investigations include testing as soon as possible during or after a fire, and early clinical consultation with a medical toxicologist.

Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats.

PubMed

Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

2017-10-01

Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of arsenic removal in batch wise water treatments by means of sequential hydride generation flow injection analysis.

PubMed

Toda, Kei; Takaki, Mari; Hashem, Md Abul

2008-08-01

Arsenic water pollution is a big issue worldwide. Determination of inorganic arsenic in each oxidation state is important because As(III) is much more toxic than As(V). An automated arsenic measurement system was developed based on complete vaporization of As by a sequential procedure and collection/preconcentration of the vaporized AsH(3), which was subsequently measured by a flow analysis. The automated sensitive method was applied to monitoring As(III) and As(V) concentrations in contaminated water standing overnight. Behaviors of arsenics were investigated in different conditions, and unique time dependence profiles were obtained. For example, in the standing of anaerobic water samples, the As(III) concentration immediately began decreasing whereas dead time was observed in the removal of As(V). In normal groundwater conditions, most arsenic was removed from the water simply by standing overnight. To obtain more effective removal, the addition of oxidants and use of steel wools were investigated. Simple batch wise treatments of arsenic contaminated water were demonstrated, and detail of the transitional changes in As(III) and As(V) were investigated.

Non-invasive urinary metabolomic profiling discriminates prostate cancer from benign prostatic hyperplasia.

PubMed

Pérez-Rambla, Clara; Puchades-Carrasco, Leonor; García-Flores, María; Rubio-Briones, José; López-Guerrero, José Antonio; Pineda-Lucena, Antonio

2017-01-01

Prostate cancer (PCa) is one of the most common malignancies in men worldwide. Serum prostate specific antigen (PSA) level has been extensively used as a biomarker to detect PCa. However, PSA is not cancer-specific and various non-malignant conditions, including benign prostatic hyperplasia (BPH), can cause a rise in PSA blood levels, thus leading to many false positive results. In this study, we evaluated the potential of urinary metabolomic profiling for discriminating PCa from BPH. Urine samples from 64 PCa patients and 51 individuals diagnosed with BPH were analysed using 1 H nuclear magnetic resonance ( 1 H-NMR). Comparative analysis of urinary metabolomic profiles was carried out using multivariate and univariate statistical approaches. The urine metabolomic profile of PCa patients is characterised by increased concentrations of branched-chain amino acids (BCAA), glutamate and pseudouridine, and decreased concentrations of glycine, dimethylglycine, fumarate and 4-imidazole-acetate compared with individuals diagnosed with BPH. PCa patients have a specific urinary metabolomic profile. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be useful to discriminate PCa from BPH in a clinical context.

Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsieh, Ru-Lan

Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (As{sup III}), arsenate (As{sup V}), monomethylarsonic acid (MMA{sup V}), and dimethylarsinic acid (DMA{sup V}) weremore » measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G + G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08–2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity. - Highlights: • AS3MT genotypes were found to affect susceptibility to developmental delay. • AS3MT rs3740392 A/G and G/G genotype had a significantly low SMI (DMA/MMA) index. • AS3MT high-risk haplotype was significantly associated with developmental delay.« less

Application of ICP-MS and HPLC-ICP-MS for diagnosis and therapy of a severe intoxication with hexavalent chromium and inorganic arsenic.

PubMed

Heitland, Peter; Blohm, Martin; Breuer, Christian; Brinkert, Florian; Achilles, Eike Gert; Pukite, Ieva; Köster, Helmut Dietrich

2017-05-01

ICP-MS and HPLC-ICP-MS were applied for diagnosis and therapeutic monitoring in a severe intoxication with a liquid containing hexavalent chromium (Cr(VI)) and inorganic arsenic (iAs). In this rare case a liver transplantation of was considered as the only chance of survival. We developed and applied methods for the determination of Cr(VI) in erythrocytes and total chromium (Cr) and arsenic (As) in blood, plasma, urine and liver tissue by ICP-MS. Exposure to iAs was diagnosed by determination of iAs species and their metabolites in urine by anion exchange HPLC-ICP-MS. Three days after ingestion of the liquid the total Cr concentrations were 2180 and 1070μg/L in whole blood and plasma, respectively, and 4540μg/L Cr(VI) in erythrocytes. The arsenic concentration in blood was 206μg/L. The urinary As species concentrations were <0.5, 109, 115, 154 and 126μg/L for arsenobetaine, As(III), As(V), methylarsonate (V) and dimethylarsinate (V), respectively. Total Cr and As concentrations in the explanted liver were 11.7 and 0.9mg/kg, respectively. Further analytical results of this case study are tabulated and provide valuable data for physicians and toxicologists. Copyright © 2017. Published by Elsevier GmbH.

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis.

PubMed

Vermassen, Tijl; Van Praet, Charles; Poelaert, Filip; Lumen, Nicolaas; Decaestecker, Karel; Hoebeke, Piet; Van Belle, Simon; Rottey, Sylvie; Delanghe, Joris

2015-01-01

Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N=66) and prostatitis patients (N=36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P<0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P<0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P<0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI)=(0.70-0.89) which was significantly better than urinary WBC count (AUC=0.70, 95% CI=[0.59-0.82], P=0.042) as isolated test. We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation.

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis

PubMed Central

Vermassen, Tijl; Van Praet, Charles; Poelaert, Filip; Lumen, Nicolaas; Decaestecker, Karel; Hoebeke, Piet; Van Belle, Simon; Rottey, Sylvie

2015-01-01

Introduction Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Materials and methods Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Results Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70–0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59–0.82], P = 0.042) as isolated test. Conclusions We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation. PMID:26526330

Environmental exposure to human carcinogens in teenagers and the association with DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franken, Carmen, E-mail: carmen.franken@vito.be

Background: We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods: Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid asmore » a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Results: Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel and t,t-muconic acid were inversely associated with the alkaline comet assay. Conclusion: This cross-sectional study found associations between current environmental exposure to (potential) human carcinogens in 14–15-year-old Flemish adolescents and short-term (oxidative) damage to DNA. Prospective follow-up will be required to investigate whether long-term effects may occur due to complex environmental exposures. - Highlights: • Exposure to (potential) carcinogens is associated with (oxidative) damage to DNA. • Most associations of exposures are with urinary 8-OHdG. • 1-Hydroxypyrene and chromium are associated with the comet assay and 8-OHdG. • PFOA is associated with higher levels of DNA damage in the alkaline comet assay.« less

Kidney function and blood pressure in preschool-aged children exposed to cadmium and arsenic - potential alleviation by selenium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skröder, Helena; Hawkesworth, Sophie; Kippler, Maria

Background: Early-life exposure to toxic compounds may cause long-lasting health effects, but few studies have investigated effects of childhood exposure to nephrotoxic metals on kidney and cardiovascular function. Objectives: To assess effects of exposure to arsenic and cadmium on kidney function and blood pressure in pre-school-aged children, and potential protection by selenium. Methods: This cross-sectional study was part of the 4.5 years of age (range: 4.4–5.4 years) follow-up of the children from a supplementation trial in pregnancy (MINIMat) in rural Bangladesh, and nested studies on early-life metal exposures. Exposure to arsenic, cadmium and selenium from food and drinking water wasmore » assessed by concentrations in children's urine, measured by ICP-MS. Kidney function was assessed by the estimated glomerular filtration rate (eGFR, n=1106), calculated from serum cystatin C, and by kidney volume, measured by ultrasound (n=375). Systolic and diastolic blood pressure was measured (n=1356) after five minutes rest. Results: Multivariable-adjusted regression analyzes showed that exposure to cadmium, but not arsenic, was inversely associated with eGFR, particularly in girls. A 0.5 µg/L increase in urinary cadmium among the girls (above spline knot at 0.12) was associated with a decrease in eGFR of 2.6 ml/min/1.73 m{sup 2}, corresponding to 0.2SD (p=0.022). A slightly weaker inverse association with cadmium was also indicated for kidney volume, but no significant associations were found with blood pressure. Stratifying on children's urinary selenium (below or above median of 12.6 µg/L) showed a three times stronger inverse association of U-Cd with eGFR (all children) in the lower selenium stratum (B=−2.8; 95% CI: −5.5, −0.20; p=0.035), compared to those with higher selenium (B=−0.79; 95% CI: −3.0, 1.4; p=0.49). Conclusions: Childhood cadmium exposure seems to adversely affect kidney function, but not blood pressure, in this population of young children in rural Bangladesh. Better selenium status appears to be protective. However, it is important to follow up these children to assess potential long-term consequences of these findings. - Highlights: • Bangladesh has high levels of arsenic and cadmium in drinking water and food • We assessed toxic exposure, kidney and cardiovascular function in Bangladeshi children • Cadmium appeared to decrease estimated glomerular filtration rate in girls • These effects were somewhat alleviated by selenium.« less

Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence

PubMed Central

2014-01-01

Background Arsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework. Methods Forty studies met the selection criteria. Seventeen provided point estimates of arsenic concentrations in drinking water and were used in a meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies) and kidney cancer mortality (2 studies). Risk estimates for incidence and mortality were analyzed separately using Generalized Linear Models. Predicted risks for bladder cancer incidence were estimated at 10, 50 and 150 μg/L arsenic in drinking water. Bootstrap randomizations were used to assess robustness of effect size. Results Twenty-eight studies observed an association between arsenic in drinking water and bladder cancer. Ten studies showed an association with kidney cancer, although of lower magnitude than that for bladder cancer. The meta-analyses showed the predicted risks for bladder cancer incidence were 2.7 [1.2–4.1]; 4.2 [2.1–6.3] and; 5.8 [2.9–8.7] for drinking water arsenic levels of 10, 50, and 150 μg/L, respectively. Bootstrapped randomizations confirmed this increased risk, but, lowering the effect size to 1.4 [0.35–4.0], 2.3 [0.59–6.4], and 3.1 [0.80–8.9]. The latter suggests that with exposures to 50 μg/L, there was an 83% probability for elevated incidence of bladder cancer; and a 74% probability for elevated mortality. For both bladder and kidney cancers, mortality rates at 150 ug/L were about 30% greater than those at 10 μg/L. Conclusion Arsenic in drinking water is associated with an increased risk of bladder and kidney cancers, although at lower levels (<150 μg/L), there is uncertainty due to the increased likelihood of exposure misclassification at the lower end of the exposure curve. Meta-analyses suggest exposure to 10 μg/L of arsenic in drinking water may double the risk of bladder cancer, or at the very least, increase it by about 40%. With the large number of people exposed to these arsenic concentrations worldwide the public health consequences of arsenic in drinking water are substantial. PMID:24889821

Global gene expression associated with hepatocarcinogenesis in adult male mice induced by in utero arsenic exposure.

PubMed

Liu, Jie; Xie, Yaxiong; Ducharme, Danica M K; Shen, Jun; Diwan, Bhalchandra A; Merrick, B Alex; Grissom, Sherry F; Tucker, Charles J; Paules, Richard S; Tennant, Raymond; Waalkes, Michael P

2006-03-01

Our previous work has shown that exposure to inorganic arsenic in utero produces hepatocellular carcinoma (HCC) in adult male mice. To explore further the molecular mechanisms of transplacental arsenic hepatocarcinogenesis, we conducted a second arsenic transplacental carcinogenesis study and used a genomewide microarray to profile arsenic-induced aberrant gene expression more extensively. Briefly, pregnant C3H mice were given drinking water containing 85 ppm arsenic as sodium arsenite or unaltered water from days 8 to 18 of gestation. The incidence of HCC in adult male offspring was increased 4-fold and tumor multiplicity 3-fold after transplacental arsenic exposure. Samples of normal liver and liver tumors were taken at autopsy for genomic analysis. Arsenic exposure in utero resulted in significant alterations (p < 0.001) in the expression of 2,010 genes in arsenic-exposed liver samples and in the expression of 2,540 genes in arsenic-induced HCC. Ingenuity Pathway Analysis revealed that significant alterations in gene expression occurred in a number of biological networks, and Myc plays a critical role in one of the primary networks. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis of selected genes/proteins showed > 90% concordance. Arsenic-altered gene expression included activation of oncogenes and HCC biomarkers, and increased expression of cell proliferation-related genes, stress proteins, and insulin-like growth factors and genes involved in cell-cell communications. Liver feminization was evidenced by increased expression of estrogen-linked genes and altered expression of genes that encode gender-related metabolic enzymes. These novel findings are in agreement with the biology and histology of arsenic-induced HCC, thereby indicating that multiple genetic events are associated with transplacental arsenic hepatocarcinogenesis.

Metal chelators and neurotoxicity: lead, mercury, and arsenic.

PubMed

Bjørklund, Geir; Mutter, Joachim; Aaseth, Jan

2017-12-01

This article reviews the clinical use of the metal chelators sodium 2,3-dimercapto-1-propanesulfonate (DMPS), meso-2,3-dimercaptosuccinic acid (DMSA), and calcium disodium edetate (CaEDTA, calcium EDTA) in overexposure and poisonings with salts of lead (Pb), mercury (Hg), and arsenic (As). DMSA has considerably lower toxicity than the classic heavy metal antagonist BAL (2,3-dimercaptopropanol) and is also less toxic than DMPS. Because of its adverse effects, CaEDTA should be replaced by DMSA as the antidote of choice in treating moderate Pb poisoning. Combination therapy with BAL and CaEDTA was previously recommended in cases of severe acute Pb poisoning with encephalopathy. We suggest that BAL in such cases acted as a shuttling Pb transporter from the intra- to the extracellular space. The present paper discusses if a combination of the extracellularly distributed DMSA with the ionophore, Monensin may provide a less toxic combination for Pb mobilization by increasing both the efflux of intracellularly deposited Pb and the urinary Pb excretion. Anyhow, oral therapy with DMSA should be continued with several intermittent courses. DMPS and DMSA are also promising antidotes in Hg poisoning, whereas DMPS seems to be a more efficient agent against As poisoning. However, new insight indicates that a combination of low-dosed BAL plus DMPS could be a preferred antidotal therapy to obtain mobilization of the intracerebral deposits into the circulation for subsequent rapid urinary excretion.

Are urinary polyaromatic hydrocarbons associated with adult hypertension, heart attack, and cancer? USA NHANES, 2011-2012.

PubMed

Shiue, Ivy

2015-11-01

Links between environmental chemicals and human health have emerged over the last few decades, but the effects from polyaromatic hydrocarbons were less studied, compared to other commonly known environmental chemicals such as heavy metals, phthalates, arsenic, phenols and pesticides. Therefore, it was aimed to study the relationships of urinary polyaromatic hydrocarbons and adult cardiovascular disease and cancer using human sample in a national and population-based study in recent years. Data was retrieved from US National Health and Nutrition Examination Surveys, 2011-2012, including demographics, self-reported health conditions and urinary polyaromatic hydrocarbons. Statistical analyses included chi-square test, t test, survey-weighted logistic regression modeling and population attributable risk (PAR) estimation. Of 5560 American adults aged 20-80 and included in the statistical analysis, urinary polyaromatic hydrocarbons (representatively in one-third sample) were observed to be higher in people with cardiovascular disease and total cancer. In particular, urinary 4-hydroxyphenanthrene was associated with hypertension (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.00-1.76, P = 0.048, PAR 5.1%), urinary 1-hydroxypyrene was significantly associated with heart attack (OR 1.47, 95%CI 1.05-2.06, P = 0.027, PAR 1.7%), and urinary 2-hydroxynapthalene (2-naphthol) was associated with cancer (OR 1.46, 95%CI 1.12-1.90, P = 0.008, PAR 3.9%). Urinary polyaromatic hydrocarbons were associated with adult hypertension, heart attack and cancer, although the causality cannot be established. From the research perspective, future studies with a longitudinal or experimental approach would be suggested. From the law and public health perspectives, regulation on minimizing exposure to polyaromatic hydrocarbons might need to be considered in future health and environmental policies and intervention programs.

Depth-resolved abundance and diversity of arsenite-oxidizing bacteria in the groundwater of Beimen, a blackfoot disease endemic area of southwestern Taiwan.

PubMed

Das, Suvendu; Kar, Sandeep; Jean, Jiin-Shuh; Rathod, Jagat; Chakraborty, Sukalyan; Liu, Hsiao-Sheng; Bundschuh, Jochen

2013-12-01

The role of arsenite oxidizers in natural attenuation of arsenic pollution necessitates studies on their abundance and diversity in arsenic-contaminated aquifers. In this study, most probable number-polymerase chain reaction (MPN-PCR) and denaturing gradient gel electrophoresis (DGGE) was applied to monitor depth-wise abundance and diversity of aerobic arsenite oxidizers in arsenic-enriched groundwater of Beimen, southwestern Taiwan. The results revealed that the abundance of arsenite oxidizers ranged from 0.04 to 0.22, and the lowest ratio was observed in the most arsenic-enriched and comparatively more reduced groundwater (depth 200 m) of Beimen 1. The highest ratio was observed in the less arsenic-enriched and less reduced groundwater (depth 60 m) of Beimen 2B. DGGE profiles showed a shift in diversity of arsenite oxidizers, consisting of members of the Betaproteobacteria (61%), Alphaproteobacteria (28%) and Gammaproteobacteria (11%), depending on mainly arsenic concentration and redox level in groundwater. Groundwater with the lowest arsenic and highest dissolved oxygen at Beimen 2B harbored 78% of the arsenite oxidizers communities, while groundwater with the highest arsenic and lowest dissolved oxygen at Beimen 1 and Beimen-Jinhu harbored 17 and 22% of arsenite oxidizers communities, respectively. Pseudomonas sp. was found only in groundwater containing high arsenic at Beimen 1 and Beimen-Jinhu, while arsenite oxidizers belonging to Alpha- and Betaproteobacteria were dominated in groundwater containing low arsenic. Copyright © 2013 Elsevier Ltd. All rights reserved.

Environmental fate of roxarsone in poultry litter. Part II. Mobility of arsenic in soils amended with poultry litter

USGS Publications Warehouse

Rutherford, D.W.; Bednar, A.J.; Garbarino, J.R.; Needham, R.; Staver, K.W.; Wershaw, R. L.

2003-01-01

Poultry litter often contains arsenic as a result of organo-arsenical feed additives. When the poultry litter is applied to agricultural fields, the arsenic is released to the environment and may result in increased arsenic in surface and groundwater and increased uptake by plants. The release of arsenic from poultry litter, litter-amended soils, and soils without litter amendment was examined by extraction with water and strong acids (HCI and HN03). The extracts were analyzed for As, C, P, Cu, Zn, and Fe. Copper, zinc, and iron are also poultry feed additives. Soils with a known history of litter application and controlled application rate of arsenic-containing poultry litter were obtained from the University of Maryland Agricultural Experiment Station. Soils from fields with long-term application of poultry litter were obtained from a tilled field on the Delmarva Peninsula (MD) and an untilled Oklahoma pasture. Samples from an adjacent forest or nearby pasture that had no history of litter application were used as controls. Depth profiles were sampled for the Oklahoma pasture soils. Analysis of the poultry litter showed that 75% of the arsenic was readily soluble in water. Extraction of soils shows that weakly bound arsenic mobilized by water correlates positively with C, P, Cu, and Zn in amended fields and appears to come primarily from the litter. Strongly bound arsenic correlates positively with Fe in amended fields and suggests sorption or coprecipitation of As and Fe in the soil column.

Early life low-level cadmium exposure is positively associated with increased oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kippler, Maria; Bakhtiar Hossain, Mohammad; Department of Laboratory Medicine, Section of Occupational and Environmental Medicine, Lund University, Lund

Environmental exposure to cadmium (Cd) is known to induce oxidative stress, a state of imbalance between the production of reactive oxygen species (ROS) and the ability to detoxify them, in adults. However, data are lacking on potential effects in early-life. We evaluated urinary concentrations of 8-oxo-7,8-dihydro-2 Prime -deoxyguanosine (8-oxodG), a recognized marker of oxidative DNA damage, in relation to Cd exposure in 96 predominantly breast-fed infants (11-17 weeks of age) in rural Bangladesh. Urinary 8-oxodG was measured using liquid chromatography tandem mass spectrometry and Cd in urine and breast milk by inductively coupled plasma mass spectrometry. Median concentration of 8-oxodGmore » was 3.9 nmol/L, urinary Cd 0.30 {mu}g/L, and breast-milk Cd 0.13 {mu}g/L. In linear regression analyses, urinary 8-oxodG was positively associated with Cd in both urine (p=0.00067) and breast milk (p=0.0021), and negatively associated with body weight (kg; p=0.0041). Adjustment for age, body weight, socio-economic status, urinary arsenic, as well as magnesium, calcium, and copper in breast milk did not change the association between Cd exposure and urinary 8-oxodG. These findings suggest that early-life low-level exposure to Cd via breast milk induces oxidative stress. Further studies are warranted to elucidate whether this oxidative stress is associated with impaired child health and development.« less

Source profiling of arsenic and heavy metals in the Selangor River basin and their maternal and cord blood levels in Selangor State, Malaysia.

PubMed

Sakai, Nobumitsu; Alsaad, Zohour; Thuong, Nguyen Thi; Shiota, Kenji; Yoneda, Minoru; Ali Mohd, Mustafa

2017-10-01

Arsenic and 5 heavy metals (nickel, copper, zinc, cadmium and lead) were quantitated in surface water (n = 18) and soil/ore samples (n = 45) collected from 5 land uses (oil palm converted from forest, oil palm in peat swamp, bare land, quarry and forest) in the Selangor River basin by inductively coupled plasma mass spectrometry (ICP-MS). Geographic information system (GIS) was used as a spatial analytical tool to classify 4 land uses (forest, agriculture/peat, urban and bare land) from a satellite image taken by Landsat 8. Source profiling of the 6 elements was conducted to identify their occurrence, their distribution and the pollution source associated with the land use. The concentrations of arsenic, cadmium and lead were also analyzed in maternal blood (n = 99) and cord blood (n = 87) specimens from 136 pregnant women collected at the University of Malaya Medical Center for elucidating maternal exposure as well as maternal-to-fetal transfer. The source profiling identified that nickel and zinc were discharged from sewage and/or industrial effluents, and that lead was discharged from mining sites. Arsenic showed a site-specific pollution in tin-tungsten deposit areas, and the pollution source could be associated with arsenopyrite. The maternal blood levels of arsenic (0.82 ± 0.61 μg/dL), cadmium (0.15 ± 0.2 μg/dL) and lead (2.6 ± 2.1 μg/dL) were not significantly high compared to their acute toxicity levels, but could have attributable risks of chronic toxicity. Those in cord blood were significantly decreased in cadmium (0.06 ± 0.07 μg/dL) and lead (0.99 ± 1.2 μg/dL) but were equivalent in arsenic (0.82 ± 1.1 μg/dL) because of the different kinetics of maternal-to-fetal transfer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nutritional Influences on One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity.

PubMed

Saxena, Roheeni; Bozack, Anne K; Gamble, Mary V

2018-05-23

Exposure to inorganic arsenic (InAs) via drinking water and/or food is a considerable worldwide problem. Methylation of InAs generates monomethyl (MMAs III+V )- and dimethyl (DMAs III+V )-arsenical species in a process that facilitates urinary As elimination; however, MMA is considerably more toxic than either InAs or DMAs. Emerging evidence suggests that incomplete methylation of As to DMAs, resulting in increased MMAs, is associated with increased risk for a host of As-related health outcomes. The biochemical pathway that provides methyl groups for As methylation, one-carbon metabolism (OCM), is influenced by folate and other micronutrients, including choline and betaine. Individuals and species differ widely in their ability to methylate As. A growing body of research, including cell-culture, animal-model, and epidemiological studies, has demonstrated the role of OCM-related micronutrients in As methylation. This review examines the evidence that nutritional status and nutritional interventions can influence the metabolism and toxicity of As, with a primary focus on folate. Expected final online publication date for the Annual Review of Nutrition Volume 38 is August 21, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Exposure to arsenic at levels found inU.S. drinking water modifies expression in the mouse lung.

PubMed

Andrew, Angeline S; Bernardo, Viviane; Warnke, Linda A; Davey, Jennifer C; Hampton, Thomas; Mason, Rebecca A; Thorpe, Jessica E; Ihnat, Michael A; Hamilton, Joshua W

2007-11-01

The mechanisms of action of drinking water arsenic in the lung and the threshold for biologic effects remain controversial. Our study utilizes Affymetrix 22,690 transcript oligonucleotide microarrays to assess the long-term effects of increasing doses of drinking water arsenic on expression levels in the mouse lung. Mice were exposed at levels commonly found in contaminated drinking water wells in the United States (0, 0.1, 1 ppb), as well as the 50 ppb former maximum contaminant level, for 5 weeks. The expression profiles revealed modification of a number of important signaling pathways, many with corroborating evidence of arsenic responsiveness. We observed statistically significant expression changes for transcripts involved in angiogenesis, lipid metabolism, oxygen transport, apoptosis, cell cycle, and immune response. Validation by reverse transcription-PCR and immunoblot assays confirmed expression changes for a subset of transcripts. These data identify arsenic-modified signaling pathways that will help guide investigations into mechanisms of arsenic's health effects and clarify the threshold for biologic effects and potential disease risk.

Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats.

PubMed

Fujioka, Masaki; Gi, Min; Kawachi, Satoko; Tatsumi, Kumiko; Ishii, Naomi; Doi, Kenichiro; Kakehashi, Anna; Wanibuchi, Hideki

2016-11-01

Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid (DMA V ) is a major urinary metabolite of sodium arsenite (iAs III ) and induces urinary bladder cancers in rats. DMA V and iAs III are negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMA V and iAs III in rat urinary bladder epithelium and liver using gpt delta F344 rats. Ten-week old male gpt delta F344 rats were randomized into 3 groups and administered 0, 92mg/L DMA V , or 87mg/L iAs III (each 50mg/L As) for 13weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection (gpt assay) and deletion mutations are identified in the red/gam genes by Spi - selection (Spi - assay). Results of the gpt and Spi - assays showed that DMA V and iAs III had no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMA V and iAs III are not mutagenic in urinary bladder epithelium or liver in rats. Copyright © 2016. Published by Elsevier B.V.

Global Gene Expression Profiling of the Asymptomatic Bacteriuria Escherichia coli Strain 83972 in the Human Urinary Tract†

PubMed Central

Roos, Viktoria; Klemm, Per

2006-01-01

Urinary tract infections (UTIs) are an important health problem worldwide, with many million cases each year. Escherichia coli is the most common organism causing UTIs in humans. The asymptomatic bacteriuria E. coli strain 83972 is an excellent colonizer of the human urinary tract, where it causes long-term bladder colonization. The strain has been used for prophylactic purposes in patients prone to more severe and recurrent UTIs. For this study, we used DNA microarrays to monitor the expression profile of strain 83972 in the human urinary tract. Significant differences in expression levels were seen between the in vivo expression profiles of strain 83972 in three patients and the corresponding in vitro expression profiles in lab medium and human urine. The data revealed an in vivo lifestyle of microaerobic growth with respiration of nitrate coupled to degradation of sugar acids and amino acids, with no signs of attachment to host tissues. Interestingly, genes involved in NO protection and metabolism showed significant up-regulation in the patients. This is one of the first studies to address bacterial whole-genome expression in humans and the first study to investigate global gene expression of an E. coli strain in the human urinary tract. PMID:16714589

Arsenic exposure, genetic susceptibility and leukocyte telomere length in an Italian young adult population.

PubMed

Borghini, Andrea; Faita, Francesca; Mercuri, Antonella; Minichilli, Fabrizio; Bustaffa, Elisa; Bianchi, Fabrizio; Andreassi, Maria Grazia

2016-09-01

Arsenic-induced health effects may be associated with critically shortened telomeres. However, few data are available on the effects of arsenic exposure on telomere length. The aim of this study was to investigate the effects of chronic arsenic exposure on leukocyte telomere length (LTL) as well as the contribution of common polymorphisms in genes implicated in arsenic metabolism (GSTT1 and GSTM1) and DNA repair (hOGG1 and XRCC1). A group of 241 healthy subjects was enrolled from four areas of Italy known to be affected by natural or anthropogenic arsenic pollution. Urine samples were tested for inorganic As (iAs), monomethylarsinic (MMA) and dimethylarsinic acid (DMA). LTL was evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Genotyping was carried out by PCR-RFLP on leukocyte DNA. In multiple linear regression analysis, LTL was significantly and inversely correlated with age (β = -0.231, P = 0.006) and showed a certain trend toward significance with iAs urinary concentration (log10 iAs, β = -0.106, P = 0.08). The genotype distribution showed significant associations between GSTT1 and the As concentration (log10 iAs, P = 0.01) and metabolite patterns (log10 DMA, P = 0.05) in the urine. However, GST genes did not interact with arsenic exposure in the modulation of LTL. Conversely, the combined presence of a higher level of iAs + MMA + DMA ≥ 19.3 μg/l (F = 6.0, P interaction = 0.01), Asi ≥ 3.86 (F = 3.9, P interaction = 0.04) μg/l, iAs + MMA + DMA ≥ 15 μg/l (F = 4.2, P interaction = 0.04) and hOGG1 Cys allele was associated with a significantly lower LTL. An interaction between XRCC1 Arg399Gln and arsenic exposure was also observed (all P interaction = 0.04). These findings suggest that telomere shortening may represent a mechanism that contributes to arsenic-related disease. The interaction of hOGG1 and XRCC1 DNA repair polymorphisms and exposure enhances telomeric DNA damage. Future studies are warranted to understand better the epidemiologic impact of arsenic on telomere function as well as to identify the subgroups of exposed subjects who need better health surveillance. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Understanding arsenic metabolism through a comparative study of arsenic levels in the urine, hair and fingernails of healthy volunteers from three unexposed ethnic groups in the United Kingdom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brima, Eid I.; Haris, Parvez I.; Jenkins, Richard O.

2006-10-01

Very little is known about arsenic (As) metabolism in healthy populations that are not exposed to high concentrations of As in their food or water. Here we present a study with healthy volunteers from three different ethnic groups, residing in Leicester, UK, which reveals statistically significant differences in the levels of total As in urine and fingernail samples. Urine (n = 63), hair (n = 36) and fingernail (n = 36) samples from Asians, Somali Black-Africans and Whites were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and graphite furnace atomic absorption spectroscopy (GF-AAS). The results clearly show that themore » total concentrations of As in urine and fingernail samples of a Somali Black-African population (urine 7.2 {mu}g/g creatinine; fingernails 723.1 {mu}g/kg) are significantly (P < 0.05) different from the Asian (urine 24.5 {mu}g/g creatinine; fingernails 153.9 {mu}g/kg) and White groups (urine 20.9 {mu}g/g creatinine; fingernails 177.0 {mu}g/kg). The chemical speciation of As in the urine of the three groups was also measured using high performance liquid chromatography coupled to ICP-MS. This showed that the proportion of the total urinary As present as dimethylarsenate (DMA) was higher for the Somali Black-African group (50%) compared to the Asians (16%) and Whites (22%). However, there was no significant difference (P > 0.05) in the level of As in the hair samples from these three groups; Somali Black-Africans (116.0 {mu}g/kg), Asians (117.4 {mu}g/kg) and Whites (141.2 {mu}g/kg). Significantly different levels of total As in fingernail and urine and a higher percentage of urinary DMA in the Somali Black-Africans are suggestive of a different pattern of As metabolism in this ethnic group.« less

Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico.

PubMed

Del Razo, Luz M; García-Vargas, Gonzalo G; Valenzuela, Olga L; Castellanos, Erika Hernández; Sánchez-Peña, Luz C; Currier, Jenna M; Drobná, Zuzana; Loomis, Dana; Stýblo, Miroslav

2011-08-24

Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico. We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity. The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance. Our study confirms a previously reported, but frequently questioned, association between exposure to iAs and diabetes, and is the first to link the risk of diabetes to the production of one of the most toxic metabolites of iAs, DMAsIII.

Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico

PubMed Central

2011-01-01

Background Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico. Methods We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity. Results The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance. Conclusions Our study confirms a previously reported, but frequently questioned, association between exposure to iAs and diabetes, and is the first to link the risk of diabetes to the production of one of the most toxic metabolites of iAs, DMAsIII. PMID:21864395

Influence of pelvic floor muscle contraction on the profile of vaginal closure pressure in continent and stress urinary incontinent women.

PubMed

Shishido, Keiichi; Peng, Qiyu; Jones, Ruth; Omata, Sadao; Constantinou, Christos E

2008-05-01

We characterized the vaginal pressure profile as a representation of closure forces along the length and circumference of the vaginal wall. Vaginal pressure profile data were used to test the hypothesis that the strength of pelvic floor muscle contractions differs significantly between continent women and women with stress urinary incontinence. Vaginal pressure profile recordings were made in 23 continent subjects and in 10 patients with stress urinary incontinence. The recordings characterized closure forces along the entire length of the vagina and identified differences among the anterior, posterior, left and right sides of the vaginal wall. Using a novel, directionally sensitive vaginal probe we made vaginal pressure profile measurements with the women at rest and during pelvic floor muscle contraction while supine. The nature of the vaginal pressure profile was characterized in terms of force distribution in the anterior and posterior vaginal walls, which was significantly greater than that on the left and right sides. The continent group had significant greater maximum pressure than the stress urinary incontinence group on the posterior side at rest (mean +/- SE 3.4 +/- 0.3 vs 2.01 +/- 0.36 N/cm(2)) and during pelvic floor muscle contraction (4.18 +/- 0.26 vs 2.25 +/- 0.41 N/cm(2)). The activity pressure difference between the posterior and anterior vaginal walls in the continent group was significantly increased when the pelvic floor muscles contracted vs that at rest (3.29 +/- 0.21 vs 2.45 +/- 0.26 N/cm(2)). However, the change observed in the stress urinary incontinence group was not significant (1.85 +/- 0.38 vs 1.35 +/- 0.27 N/cm(2)). The results demonstrate that the voluntary pelvic floor muscles impose significant closure forces along the vaginal wall of continent women but not in women with stress urinary incontinence. The implication of these findings is that extrinsic urethral closure pressure is insufficiently augmented by pelvic floor muscle contraction in women with stress urinary incontinence.

Effects of co-administration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium.

PubMed

Suzuki, Shugo; Arnold, Lora L; Pennington, Karen L; Kakiuchi-Kiyota, Satoko; Cohen, Samuel M

2009-06-30

Arsenite (As(III)), an inorganic arsenical, is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. Oxidative stress has been suggested as a mechanism for arsenic-induced carcinogenesis. Reactive oxygen species (ROS) can be important factors for carcinogenesis and tumor progression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is known to produce intracellular ROS, therefore, we investigated the ability of apocynin (acetovanillone), an NADPH oxidase inhibitor, to inhibit the cytotoxicity and regenerative cell proliferation of arsenic in vitro and in vivo. Apocynin had similar effects in reducing the cytotoxicity of As(III) and dimethylarsinous acid (DMA(III)) in rat urothelial cells in vitro. When tested at the same concentrations as apocynin, other antioxidants, such as l-ascorbate and N-acetylcysteine, did not inhibit As(III)-induced cytotoxicity but they were more effective at inhibiting DMA(III)-induced cytotoxicity compared with apocynin. In vivo, female rats were treated for 3 weeks with 100ppm As(III). Immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) showed that apocynin reduced oxidative stress partially induced by As(III) treatment on rat urothelium, and significantly reduced the cytotoxicity of superficial cells detected by scanning electron microscopy (SEM). However, based on the incidence of simple hyperplasia and the bromodeoxyuridine (BrdU) labeling index, apocynin did not inhibit As(III)-induced urothelial cell proliferation. These data suggest that the NADPH oxidase inhibitor, apocynin, may have the ability to partially inhibit arsenic-induced oxidative stress and cytotoxicity of the rat bladder epithelium in vitro and in vivo. However, apocynin did not inhibit the regenerative cell proliferation induced by arsenite in a short-term study.

Physical setting and natural sources of exposure to carcinogenic trace elements and radionuclides in Lahontan Valley, Nevada

USGS Publications Warehouse

Seiler, Ralph L.

2012-01-01

In Lahontan Valley, Nevada, arsenic, cobalt, tungsten, uranium, radon, and polonium-210 are carcinogens that occur naturally in sediments and groundwater. Arsenic and cobalt are principally derived from erosion of volcanic rocks in the local mountains and tungsten and uranium are derived from erosion of granitic rocks in headwater reaches of the Carson River. Radon and 210Po originate from radioactive decay of uranium in the sediments. Arsenic, aluminum, cobalt, iron, and manganese concentrations in household dust suggest it is derived from the local soils. Excess zinc and chromium in the dust are probably derived from the vacuum cleaner used to collect the dust, or household sources such as the furnace. Some samples have more than 5 times more cobalt in the dust than in the local soil, but whether the source of the excess cobalt is anthropogenic or natural cannot be determined with the available data. Cobalt concentrations are low in groundwater, but arsenic, uranium, radon, and 210Po concentrations often exceed human-health standards, and sometime greatly exceed them. Exposure to radon and its decay products in drinking water can vary significantly depending on when during the day that the water is consumed. Although the data suggests there have been no long term changes in groundwater chemistry that corresponds to the Lahontan Valley leukemia cluster, the occurrence of the very unusual leukemia cluster in an area with numerous 210Po and arsenic contaminated wells is striking, particularly in conjunction with the exceptionally high levels of urinary tungsten in Lahontan Valley residents. Additional research is needed on potential exposure pathways involving food or inhalation, and on synergistic effects of mixtures of these natural contaminants on susceptibility to development of leukemia.

Physical setting and natural sources of exposure to carcinogenic trace elements and radionuclides in Lahontan Valley, Nevada.

PubMed

Seiler, Ralph

2012-04-05

In Lahontan Valley, Nevada, arsenic, cobalt, tungsten, uranium, radon, and polonium-210 are carcinogens that occur naturally in sediments and groundwater. Arsenic and cobalt are principally derived from erosion of volcanic rocks in the local mountains and tungsten and uranium are derived from erosion of granitic rocks in headwater reaches of the Carson River. Radon and 210Po originate from radioactive decay of uranium in the sediments. Arsenic, aluminum, cobalt, iron, and manganese concentrations in household dust suggest it is derived from the local soils. Excess zinc and chromium in the dust are probably derived from the vacuum cleaner used to collect the dust, or household sources such as the furnace. Some samples have more than 5 times more cobalt in the dust than in the local soil, but whether the source of the excess cobalt is anthropogenic or natural cannot be determined with the available data. Cobalt concentrations are low in groundwater, but arsenic, uranium, radon, and 210Po concentrations often exceed human-health standards, and sometime greatly exceed them. Exposure to radon and its decay products in drinking water can vary significantly depending on when during the day that the water is consumed. Although the data suggests there have been no long term changes in groundwater chemistry that corresponds to the Lahontan Valley leukemia cluster, the occurrence of the very unusual leukemia cluster in an area with numerous 210Po and arsenic contaminated wells is striking, particularly in conjunction with the exceptionally high levels of urinary tungsten in Lahontan Valley residents. Additional research is needed on potential exposure pathways involving food or inhalation, and on synergistic effects of mixtures of these natural contaminants on susceptibility to development of leukemia. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effects of As2O3 on DNA methylation, genomic instability, and LTR retrotransposon polymorphism in Zea mays.

PubMed

Erturk, Filiz Aygun; Aydin, Murat; Sigmaz, Burcu; Taspinar, M Sinan; Arslan, Esra; Agar, Guleray; Yagci, Semra

2015-12-01

Arsenic is a well-known toxic substance on the living organisms. However, limited efforts have been made to study its DNA methylation, genomic instability, and long terminal repeat (LTR) retrotransposon polymorphism causing properties in different crops. In the present study, effects of As2O3 (arsenic trioxide) on LTR retrotransposon polymorphism and DNA methylation as well as DNA damage in Zea mays seedlings were investigated. The results showed that all of arsenic doses caused a decreasing genomic template stability (GTS) and an increasing Random Amplified Polymorphic DNAs (RAPDs) profile changes (DNA damage). In addition, increasing DNA methylation and LTR retrotransposon polymorphism characterized a model to explain the epigenetically changes in the gene expression were also found. The results of this experiment have clearly shown that arsenic has epigenetic effect as well as its genotoxic effect. Especially, the increasing of polymorphism of some LTR retrotransposon under arsenic stress may be a part of the defense system against the stress.

Effects of Orally Ingested Arsenic on Respiratory Epithelial Permeability to Bacteria and Small Molecules in Mice

PubMed Central

Madenspacher, Jennifer H.; Whitehead, Gregory S.; Thomas, Seddon Y.; Aloor, Jim J.; Gowdy, Kymberly M.; Fessler, Michael B.

2017-01-01

Background: Arsenic exposure via drinking water impacts millions of people worldwide. Although arsenic has been associated epidemiologically with increased lung infections, the identity of the lung cell types targeted by peroral arsenic and the associated immune mechanisms remain poorly defined. Objectives: We aimed to determine the impact of peroral arsenic on pulmonary antibacterial host defense. Methods: Female C57BL/6 mice were administered drinking water with 0, 250 ppb, or 25 ppm sodium arsenite for 5 wk and then challenged intratracheally with Klebsiella pneumoniae, Streptococcus pneumoniae, or lipopolysaccharide. Bacterial clearance and immune responses were profiled. Results: Arsenic had no effect on bacterial clearance in the lung or on the intrapulmonary innate immune response to bacteria or lipopolysaccharide, as assessed by neutrophil recruitment to, and cytokine induction in, the airspace. Alveolar macrophage TNFα production was unaltered. By contrast, arsenic-exposed mice had significantly reduced plasma TNFα in response to systemic lipopolysaccharide challenge, together suggesting that the local airway innate immune response may be relatively preserved from arsenic intoxication. Despite intact intrapulmonary bacterial clearance during pneumonia, arsenic-exposed mice suffered dramatically increased bacterial dissemination to the bloodstream. Mechanistically, this was linked to increased respiratory epithelial permeability, as revealed by intratracheal FITC-dextran tracking, serum Club Cell protein 16 measurement, and other approaches. Consistent with barrier disruption at the alveolar level, arsenic-exposed mice had evidence for alveolar epithelial type 1 cell injury. Conclusions: Peroral arsenic has little effect on local airway immune responses to bacteria but compromises respiratory epithelial barrier integrity, increasing systemic translocation of inhaled pathogens and small molecules. https://doi.org/10.1289/EHP1878 PMID:28960179

Arsenic Exposure Is Associated with Decreased DNA Repair in Vitro and in Individuals Exposed to Drinking Water Arsenic

PubMed Central

Andrew, Angeline S.; Burgess, Jefferey L.; Meza, Maria M.; Demidenko, Eugene; Waugh, Mary G.; Hamilton, Joshua W.; Karagas, Margaret R.

2006-01-01

The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora (Mexico). Additionally, in corroborative laboratory studies, we examined the effects of As on DNA repair in a cultured human cell model. Arsenic exposure was associated with decreased expression of ERCC1 in isolated lymphocytes at the mRNA and protein levels. In addition, lymphocytes from As-exposed individuals showed higher levels of DNA damage, as measured by a comet assay, both at baseline and after a 2-acetoxyacetylaminofluorene (2-AAAF) challenge. In support of the in vivo data, As exposure decreased ERCC1 mRNA expression and enhanced levels of DNA damage after a 2-AAAF challenge in cell culture. These data provide further evidence to support the ability of As to inhibit the DNA repair machinery, which is likely to enhance the genotoxicity and mutagenicity of other directly genotoxic compounds, as part of a cocarcinogenic mechanism of action. PMID:16882524

Characterization of Arsenic Contamination on Rust from Ton Containers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gary S. Groenewold; Recep Avci; Robert V. Fox

The speciation and spatial distribution of arsenic on rusted steel surfaces affects both measurement and removal approaches. The chemistry of arsenic residing in the rust of ton containers that held the chemical warfare agents bis(2-chloroethyl)sulfide (sulfur mustard) and 2-chlorovinyldichloroarsine (Lewisite) is of particular interest, because while the agents have been decontaminated, residual arsenic could pose a health or environmental risk. The chemistry and distribution of arsenic in rust samples was probed using imaging secondary ion mass spectrometry (SIMS), X-ray photoelectron spectroscopy (XPS), Auger electron spectroscopy, and scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX). Arsenic in the +3 and or +5more » oxidation state is homogeneously distributed at the very top-most layer of the rust samples, and is intimately associated with iron. Sputter depth profiling followed by SIMS and XPS shows As at a depth of several nm, in some cases in a reduced form. The SEM/EDX experiments show that As is present at a depth of several microns, but is inhomogeneously distributed; most locations contained oxidized As at concentrations of a few percent, however several locations showed very high As in a metallic form. These results indicate that the rust material must be removed if the steel containers are to be cleared of arsenic.« less

Association of urinary metals levels with type 2 diabetes risk in coke oven workers.

PubMed

Liu, Bing; Feng, Wei; Wang, Jing; Li, Yaru; Han, Xu; Hu, Hua; Guo, Huan; Zhang, Xiaomin; He, Meian

2016-03-01

Studies indicated that occupationally exposed to metals could result in oxidative damage and inflammation and increase cardiovascular diseases risk. However, epidemiological studies about the associations of metals exposure with diabetes risk among coke oven workers were limited. This study aims to investigate the potential associations of 23 metals levels with the risk of diabetes among coke oven workers. The analysis was conducted in a cross-sectional study including 1493 participants. Urinary metals and urinary polycyclic aromatic hydrocarbons (PAHs) metabolites levels were determined by inductively coupled plasma mass spectrometer and gas chromatograph-mass spectrometer respectively. Multivariate logistic regression was used to investigate the associations of urinary metal levels with diabetes risk with adjustment for potential confounding factors including gender, age, BMI, education, smoking, drinking, physical activity, hypertension, hyperlipidemia and urinary PAHs metabolites levels. Compared with the normoglycemia group, the levels of urinary copper, zinc, arsenic, selenium, molybdenum, and cadmium were significantly higher in the diabetes group (all p < 0.05). Participants with the highest tertile of urinary copper and zinc had 2.12 (95%CI: 1.12-4.01) and 5.43 (95%CI: 2.61-11.30) fold risk of diabetes. Similar results were found for hyperglycemia risk. Besides, participants with the highest tertile of manganese, barium, and lead had 1.65(1.22-2.23), 1.60(1.19-2.16) and 1.45(1.05-1.99) fold risk of hyperglycemia when compared with the lowest tertlie. The results indicated that the urinary copper and zinc levels were positively associated with the risk of diabetes and hyperglycemia among coke oven workers. Urinary manganese, barium and lead levels were also associated with increased risk of hyperglycemia independently of other traditional risk factors. These findings need further validation in prospective study with larger sample size. Copyright © 2015 Elsevier Ltd. All rights reserved.

Trace elements are associated with urinary 8-hydroxy-2'-deoxyguanosine level: a case study of college students in Guangzhou, China.

PubMed

Lu, Shaoyou; Ren, Lu; Fang, Jianzhang; Ji, Jiajia; Liu, Guihua; Zhang, Jianqing; Zhang, Huimin; Luo, Ruorong; Lin, Kai; Fan, Ruifang

2016-05-01

Many trace heavy elements are carcinogenic and increase the incidence of cancer. However, a comprehensive study of the correlation between multiple trace elements and DNA oxidative damage is still lacking. The aim of this study is to investigate the relationships between the body burden of multiple trace elements and DNA oxidative stress in college students in Guangzhou, China. Seventeen trace elements in urine samples were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative stress, was also measured using liquid chromatography tandem mass spectrometer (LC-MS/MS). The concentrations of six essential elements including manganese (Mn), copper (Cu), nickel (Ni), selenium (Se), strontium (Sr), and molybdenum (Mo), and five non-essential elements including arsenic (As), cadmium (Cd), aluminum (Al), stibium (Sb), and thallium (Tl), were found to be significantly correlated with urinary 8-OHdG levels. Moreover, urinary levels of Ni, Se, Mo, As, Sr, and Tl were strongly significantly correlated with 8-OHdG (P < 0.01) concentration. Environmental exposure and dietary intake of these trace elements may play important roles in DNA oxidative damage in the population of Guangzhou, China.

Human urinary excretion profile after smoking and oral administration of ( sup 14 C)delta 1-tetrahydrocannabinol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johansson, E.; Gillespie, H.K.; Halldin, M.M.

The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of ({sup 14}C)delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of {sup 14}C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings weremore » similar to the excretion profile of {sup 14}C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively.« less

The Urinary Bladder Transcriptome and Proteome Defined by Transcriptomics and Antibody-Based Profiling

PubMed Central

Habuka, Masato; Fagerberg, Linn; Hallström, Björn M.; Pontén, Fredrik; Yamamoto, Tadashi; Uhlen, Mathias

2015-01-01

To understand functions and diseases of urinary bladder, it is important to define its molecular constituents and their roles in urinary bladder biology. Here, we performed genome-wide deep RNA sequencing analysis of human urinary bladder samples and identified genes up-regulated in the urinary bladder by comparing the transcriptome data to those of all other major human tissue types. 90 protein-coding genes were elevated in the urinary bladder, either with enhanced expression uniquely in the urinary bladder or elevated expression together with at least one other tissue (group enriched). We further examined the localization of these proteins by immunohistochemistry and tissue microarrays and 20 of these 90 proteins were localized to the whole urothelium with a majority not yet described in the context of the urinary bladder. Four additional proteins were found specifically in the umbrella cells (Uroplakin 1a, 2, 3a, and 3b), and three in the intermediate/basal cells (KRT17, PCP4L1 and ATP1A4). 61 of the 90 elevated genes have not been previously described in the context of urinary bladder and the corresponding proteins are interesting targets for more in-depth studies. In summary, an integrated omics approach using transcriptomics and antibody-based profiling has been used to define a comprehensive list of proteins elevated in the urinary bladder. PMID:26694548

Metal mixtures in urban and rural populations in the US: The Multi-Ethnic Study of Atherosclerosis and the Strong Heart Study.

PubMed

Pang, Yuanjie; Peng, Roger D; Jones, Miranda R; Francesconi, Kevin A; Goessler, Walter; Howard, Barbara V; Umans, Jason G; Best, Lyle G; Guallar, Eliseo; Post, Wendy S; Kaufman, Joel D; Vaidya, Dhananjay; Navas-Acien, Ana

2016-05-01

Natural and anthropogenic sources of metal exposure differ for urban and rural residents. We searched to identify patterns of metal mixtures which could suggest common environmental sources and/or metabolic pathways of different urinary metals, and compared metal-mixtures in two population-based studies from urban/sub-urban and rural/town areas in the US: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Strong Heart Study (SHS). We studied a random sample of 308 White, Black, Chinese-American, and Hispanic participants in MESA (2000-2002) and 277 American Indian participants in SHS (1998-2003). We used principal component analysis (PCA), cluster analysis (CA), and linear discriminant analysis (LDA) to evaluate nine urinary metals (antimony [Sb], arsenic [As], cadmium [Cd], lead [Pb], molybdenum [Mo], selenium [Se], tungsten [W], uranium [U] and zinc [Zn]). For arsenic, we used the sum of inorganic and methylated species (∑As). All nine urinary metals were higher in SHS compared to MESA participants. PCA and CA revealed the same patterns in SHS, suggesting 4 distinct principal components (PC) or clusters (∑As-U-W, Pb-Sb, Cd-Zn, Mo-Se). In MESA, CA showed 2 large clusters (∑As-Mo-Sb-U-W, Cd-Pb-Se-Zn), while PCA showed 4 PCs (Sb-U-W, Pb-Se-Zn, Cd-Mo, ∑As). LDA indicated that ∑As, U, W, and Zn were the most discriminant variables distinguishing MESA and SHS participants. In SHS, the ∑As-U-W cluster and PC might reflect groundwater contamination in rural areas, and the Cd-Zn cluster and PC could reflect common sources from meat products or metabolic interactions. Among the metals assayed, ∑As, U, W and Zn differed the most between MESA and SHS, possibly reflecting disproportionate exposure from drinking water and perhaps food in rural Native communities compared to urban communities around the US. Copyright © 2016 Elsevier Inc. All rights reserved.

What is the best biomarker to assess arsenic exposure via drinking water?

PubMed

Marchiset-Ferlay, Nathalie; Savanovitch, Chantal; Sauvant-Rochat, Marie-Pierre

2012-02-01

Arsenic (As) is a ubiquitous element. The current WHO guideline for As in drinking water is 10 μg/L. Furthermore, about 130 million people have only access to drinking water containing more than 10 g As/L. Although numerous studies have shown the related adverse effects of As, sensitive appropriate biomarkers are still required for studies of environmental epidemiology. A review of the literature has shown that various biomarkers are used for such research. Their limits and advantages are highlighted in this paper: (i) the detection of As or its derivatives in the blood is an indication of the dose ingested but it is not evidence of chronic intoxication. (ii) The detection of As in urine is an indispensible procedure because it is a good marker for internal dose. It has been demonstrated to correlate well for a number of chronic effects related to As levels in drinking water. However confounding factors must be taken into account to avoid misinterpretation and this may require As speciation. (iii) As in the hair and nails reflects the level of long term exposure but it is difficult to relate the level with the dose ingested. (iv) Some studies showed a correlation between urinary As and urinary and blood porphyrins. However, it is difficult to use only porphyrins as a biomarker in a population survey carried out without doing further studies. (v) Genotoxic effects are based on the characterization of these potential effects. Most studies have detected increases in DNA damage, sister chromatid exchange, micronuclei or chromosomal aberrations in populations exposed to As in drinking water. Micronuclei assay is the technique of choice to follow these populations, because it is sensitive and easy to use. To conclude, whatever epidemiological studies are, the urinary and toenail biomarkers are useful to provide indications of internal dose. Moreover, micronuclei assay can be complementary use as biomarker of early effects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Human health risks and socio-economic perspectives of arsenic exposure in Bangladesh: A scoping review.

PubMed

Rahman, M Azizur; Rahman, A; Khan, M Zaved Kaiser; Renzaho, Andre M N

2018-04-15

Arsenic contamination of drinking water, which can occur naturally or because of human activities such as mining, is the single most important public health issue in Bangladesh. Fifty out of the 64 districts in the country have arsenic concentration of groundwater exceeding 50µgL -1 , the Bangladeshi threshold, affecting 35-77 million people or 21-48% of the total population. Chronic arsenic exposure through drinking water and other dietary sources is an important public health issue worldwide affecting hundreds of millions of people. Consequently, arsenic poisoning has attracted the attention of researchers and has been profiled extensively in the literature. Most of the literature has focused on characterising arsenic poisoning and factors associated with it. However, studies examining the socio-economic aspects of chronic exposure of arsenic through either drinking water or foods remain underexplored. The objectives of this paper are (i) to review arsenic exposure pathways to humans; (ii) to summarise public health impacts of chronic arsenic exposure; and (iii) to examine socio-economic implications and consequences of arsenicosis with a focus on Bangladesh. This scoping review evaluates the contributions of different exposure pathways by analysing arsenic concentrations in dietary and non-dietary sources. The socio-economic consequences of arsenicosis disease in Bangladesh are discussed in this review by considering food habits, nutritional status, socio-economic conditions, and socio-cultural behaviours of the people of the country. The pathways of arsenic exposure in Bangladesh include drinking water, various plant foods and non-dietary sources such as soil. Arsenic affected people are often abandoned by the society, lose their jobs and get divorced and are forced to live a sub-standard life. The fragile public health system in Bangladesh has been burdened by the management of thousands of arsenicosis victims in Bangladesh. Copyright © 2017 Elsevier Inc. All rights reserved.

Determination and pharmacokinetic properties of arsenic speciation in Xiao-Er-Zhi-Bao-Wan by high-performance liquid chromatography with inductively coupled plasma mass spectrometry.

PubMed

Han, Xu; Luo, Jiaoyang; Zhou, Wenju; Yang, Shihai; Yang, Meihua

2016-10-01

A method of high performance liquid chromatography with a Hamilton PRP-X100 ion-exchange column (250 × 4.1 mm id, 10 μm) coupled to inductively coupled plasma mass spectrometry was employed to generate a full concentration-time profile of arsenic speciation after oral administration. The results exhibited good linearity and revealed that, in the pills, the average arsenic concentration was 10105.4 ± 380.7 mg/kg, and in the water extraction solution, the inorganic As(III) and As(V) concentrations were 220.1 ± 12.6 and 45.5 ± 2.3 mg/kg, respectively. No trace of monomethyl arsenic acid was detected in any of the plasma samples. We then successfully applied the established methodology to examine the pharmacokinetics of arsenic speciation. The resulting data revealed that, after oral administration in rats, the plasma concentration of each arsenic species reached C max shortly after initial dosing, and that the distribution and elimination of As(V) was faster than that of As(III) and dimethyl arsenic acid. Additionally, the t 1/2 values of As(V), As(III), and dimethyl arsenic acid were 3.4 ± 1.6, 14.3 ± 4.0, and 19.9 ± 1.6 h, respectively. This study provides references for the determination of arsenic speciation in mineral-containing medicines and could serve as a useful tool in measuring the true toxicity in traditional medicines that contain them. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The medicinal use of realgar (As₄S₄) and its recent development as an anticancer agent.

PubMed

Wu, Jinzhu; Shao, Yanbin; Liu, Jialiang; Chen, Gang; Ho, Paul C

2011-06-01

Arsenicals have been known as poisons and paradoxically as therapeutic agents. In the early 1970s, Chinese physicians from Harbin revived the medicinal use of arsenicals as anticancer agents. Notable success was observed in the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO). The FDA approved ATO injection in the year 2000 for the treatment of APL. In contrast, the clinical use of the other arsenical, realgar (As₄S₄), is currently much less established, though it has also long been used in medical history. According to ancient medical records and recent findings in clinical trials, realgar was found as effective as ATO, but with relatively good oral safety profiles even on chronic administration. These give realgar an advantage over ATO in maintenance treatment. Though there is increasing understanding on the mechanisms of action and metabolic profiles of ATO, similar aspects of realgar are unclear to date. We outline the use of realgar in traditional medicines, especially in traditional Chinese medicines (TCM) from ancient times to present. The clinical and experimental observations on realgar as a therapeutic agent are described with an emphasis on those findings that may imply the rationale and future directions of realgar as a potential anticancer drug candidate. There is an increasing understanding in the mechanisms of action of realgar as an antileukemic agent. However, there is still sparse information on its metabolism and toxicity profiles. Realgar is poorly soluble in water. Recently, several types of realgar nanoparticles (NPs) have been developed. Some of these realgar NPs also possess the unique optical properties of quantum dots. The activities and bioavailability of realgar NPs are much influenced by their sizes, making realgar an interesting biomedical and pharmaceutical research candidate. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Arsenic and Other Metals’ Presence in Biomarkers of Cambodians in Arsenic Contaminated Areas

PubMed Central

Chanpiwat, Penradee; Himeno, Seiichiro; Sthiannopkao, Suthipong

2015-01-01

Chemical analyses of metal (Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Mo, Ba, and Pb) concentrations in hair, nails, and urine of Cambodians in arsenic-contaminated areas who consumed groundwater daily showed elevated levels in these biomarkers for most metals of toxicological interest. The levels of metals in biomarkers corresponded to their levels in groundwater, especially for As, whose concentrations exceeded the WHO guidelines for drinking water. About 75.6% of hair samples from the population in this study contained As levels higher than the normal level in unexposed individuals (1 mg·kg−1). Most of the population (83.3%) showed As urinary levels exceeding the normal (<50 ng·mg−1). These results indicate the possibility of arsenicosis symptoms in residents of the areas studied. Among the three biomarkers tested, hair has shown to be a reliable indicator of metal exposures. The levels of As (r2 = 0.633), Ba (r2 = 0.646), Fe (r2 = 0.595), and Mo (r2 = 0.555) in hair were strongly positively associated with the levels of those metals in groundwater. In addition, significant weak correlations (p < 0.01) were found between levels of exposure to As and As concentrations in both nails (r2 = 0.544) and urine (r2 = 0.243). PMID:26569276

Exposure Assessment to Environmental Chemicals in Children from Ciudad Juarez, Chihuahua, Mexico.

PubMed

Ochoa-Martinez, Angeles C; Orta-Garcia, Sandra T; Rico-Escobar, Edna M; Carrizales-Yañez, Leticia; Del Campo, Jorge D Martin; Pruneda-Alvarez, Lucia G; Ruiz-Vera, Tania; Gonzalez-Palomo, Ana K; Piña-Lopez, Iris G; Torres-Dosal, Arturo; Pérez-Maldonado, Ivan N

2016-05-01

It has been demonstrated that the human biomonitoring of susceptible populations is a valuable method for the identification of critical contaminants. Therefore, the purpose of this study was to assess the exposure profile for arsenic (As), lead (Pb), mercury (Hg), 1-hydroxypyrene (1-OHP), 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) in children living in Ciudad Juarez, Chihuahua, Mexico (a major manufacturing center in Mexico). In 2012, we evaluated a total of 135 healthy children living in Ciudad Juarez since birth. The total PBDEs levels ranged from nondetectable (< LOD) to 215 ng/g lipid, with a mean total PBDEs level of 29.5 ± 53.0 ng/g lipid (geometric mean ± standard deviation). The mean total PCBs level in the study participants was 29.0 ± 10.5 ng/g lipid (range 4.50-50.0 ng/g lipid). The mean concentration of total DDT (DDT + DDE) was 11.9 ± 6.70 ng/g lipid (range 3.00-26.0 ng/g lipid). The mean 1-OHP levels was 1.2 ± 1.1 µmol/mol creatinine (range

Statistical analysis of arsenic contamination in drinking water in a city of Iran and its modeling using GIS.

PubMed

Sadeghi, Fatemeh; Nasseri, Simin; Mosaferi, Mohammad; Nabizadeh, Ramin; Yunesian, Masud; Mesdaghinia, Alireza

2017-05-01

In this research, probable arsenic contamination in drinking water in the city of Ardabil was studied in 163 samples during four seasons. In each season, sampling was carried out randomly in the study area. Results were analyzed statistically applying SPSS 19 software, and the data was also modeled by Arc GIS 10.1 software. The maximum permissible arsenic concentration in drinking water defined by the World Health Organization and Iranian national standard is 10 μg/L. Statistical analysis showed 75, 88, 47, and 69% of samples in autumn, winter, spring, and summer, respectively, had concentrations higher than the national standard. The mean concentrations of arsenic in autumn, winter, spring, and summer were 19.89, 15.9, 10.87, and 14.6 μg/L, respectively, and the overall average in all samples through the year was 15.32 μg/L. Although GIS outputs indicated that the concentration distribution profiles changed in four consecutive seasons, variance analysis of the results showed that statistically there is no significant difference in arsenic levels in four seasons.

Bacteria-mediated arsenic oxidation and reduction in the growth media of arsenic hyperaccumulator Pteris vittata.

PubMed

Wang, Xin; Rathinasabapathi, Bala; de Oliveira, Letuzia Maria; Guilherme, Luiz R G; Ma, Lena Q

2012-10-16

Microbes play an important role in arsenic transformation and cycling in the environment. Microbial arsenic oxidation and reduction were demonstrated in the growth media of arsenic hyperaccumulator Pteris vittata L. All arsenite (AsIII) at 0.1 mM in the media was oxidized after 48 h incubation. Oxidation was largely inhibited by antibiotics, indicating that bacteria played a dominant role. To identify AsIII oxidizing bacteria, degenerate primers were used to amplify ∼500 bp of the AsIII oxidase gene aioA (aroA) using DNA extracted from the media. One aioA (aroA)-like sequence (MG-1, tentatively identified as Acinetobacter sp.) was amplified, exhibiting 82% and 91% identity in terms of gene and deduced protein sequence to those from Acinetobacter sp. 33. In addition, four bacterial strains with different arsenic tolerance were isolated and identified as Comamonas sp.C-1, Flavobacterium sp. C-2, Staphylococcus sp. C-3, and Pseudomonas sp. C-4 using carbon utilization, fatty acid profiles, and/or sequencing 16s rRNA gene. These isolates exhibited dual capacity for both AsV reduction and AsIII oxidation under ambient conditions. Arsenic-resistant bacteria with strong AsIII oxidizing ability may have potential to improve bioremediation of AsIII-contaminated water using P. vittata and/or other biochemical strategies.

Maternal/fetal metabolomes appear to mediate the impact of arsenic exposure on birth weight: A pilot study.

PubMed

Wei, Yongyue; Shi, Qianwen; Wang, Zhaoxi; Zhang, Ruyang; Su, Li; Quamruzzaman, Quazi; Rahman, Mahmuder; Chen, Feng; Christiani, David C

2017-05-01

Arsenic exposure has been associated with low birth weight. However, the underlying mechanisms are not well understood. Alterations to metabolites may act as causal mediators of the effect of arsenic exposure on low birth weight. This pilot study aimed to explore the role of metabolites in mediating the association of arsenic exposure on infant birth weight. Study samples were selected from a well-established prospectively enrolled cohort in Bangladesh comprising 35 newborns and a subset of 20 matched mothers. Metabolomics profiling was performed on 35 cord blood samples and 20 maternal peripheral blood samples collected during the second trimester of pregnancy. Inorganic arsenic (iAs) exposure was evaluated via cord blood samples and maternal toenail samples collected during the first trimester. Multiple linear regression and mediation analyses were used to explore the relationship between iAs exposure, metabolite alterations, and low birth weight. Cord blood arsenic level was correlated with elevated levels of 17-methylstearate, laurate (12:0) and 4-vinylphenol sulfate along with lower birth weight. Prenatal maternal toenail iAs level was associated with two peripheral blood metabolites (butyrylqlycine and tartarate), which likely contributed to higher cord blood iAs levels both independently and interactively. Findings of this pilot study indicate that both intrauterine and maternal peripheral blood metabolites appear to influence the toxic effect of inorganic arsenic exposure on low birth weight.

Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet's Disease by Gas Chromatography/Time-of-Flight-Mass Spectrometry.

PubMed

Ahn, Joong Kyong; Kim, Jungyeon; Hwang, Jiwon; Song, Juhwan; Kim, Kyoung Heon; Cha, Hoon-Suk

2017-11-02

Diagnosing Behcet's disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC/TOF-MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF-MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA) model were R ² X of 0.231, R ² Y of 0.804, and Q ² of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974). OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%). We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF-MS.

Biomonitoring of arsenic, cadmium, lead, manganese and mercury in urine and hair of children living near mining and industrial areas.

PubMed

Molina-Villalba, Isabel; Lacasaña, Marina; Rodríguez-Barranco, Miguel; Hernández, Antonio F; Gonzalez-Alzaga, Beatriz; Aguilar-Garduño, Clemente; Gil, Fernando

2015-04-01

Huelva (South West Spain) and its surrounding municipalities represent one of the most polluted estuaries in the world owing to the discharge of mining and industrial related pollutants in their proximity. A biomonitoring study was conducted to assess exposure to arsenic and some trace metals (cadmium, mercury, manganese and lead) in urine and scalp hair from a representative sample of children aged 6-9 years (n=261). This is the only study simultaneously analyzing those five metal elements in children urine and hair. The potential contribution of gender, water consumption, residence area and body mass index on urinary and hair metal concentrations was also studied. Urine levels of cadmium and total mercury in a proportion (25-50%) of our children population living near industrial/mining areas might have an impact on health, likely due to environmental exposure to metal pollution. The only significant correlation between urine and hair levels was found for mercury. Children living near agriculture areas showed increased levels of cadmium and manganese (in urine) and arsenic (in hair). In contrast, decreased urine Hg concentrations were observed in children living near mining areas. Girls exhibited significantly higher trace metal concentrations in hair than boys. The greatest urine arsenic concentrations were found in children drinking well/spring water. Although human hair can be a useful tool for biomonitoring temporal changes in metal concentrations, levels are not correlated with those found in urine except for total mercury, thus providing additional information. Copyright © 2014 Elsevier Ltd. All rights reserved.

Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dheer, Rishu; Patterson, Jena; Dudash, Mark

Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low)more » or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. - Highlights: • Arsenic exposure induces changes in host and host nitrogen metabolism that cause progresive change in the microbiome. • A polyphasic approach reveals changes in microbial community structure, composition and nitrite reductase expression. • The profile of nitrogen and nitroamino acid change caused by arsenic may relect increased risk of cardiovascular pathogenesis.« less

A high-selenium lentil dietary intervention in Bangladesh to counteract arsenic toxicity: study protocol for a randomized controlled trial.

PubMed

Krohn, Regina M; Raqib, Rubhana; Akhtar, Evana; Vandenberg, Albert; Smits, Judit E G

2016-04-27

Millions of people worldwide are exposed to dangerous levels of arsenic (above the WHO water standard of 10 ppb) in drinking water and food. Lack of nutritious foods exacerbates the adverse health effects of arsenic poisoning. The micronutrient selenium is a known antagonist to arsenic, promoting the excretion of arsenic from the body. Studies are in progress examining the potential of using selenium supplement pills to counteract arsenic toxicity. We are planning a clinical trial to test whether high-selenium lentils, as a whole food solution, can improve the health of arsenic-exposed Bangladeshi villagers. A total of 400 participants (about 80 families) will be divided into two groups via computer-generated block randomization. Eligibility criteria are age (≥14) years) and arsenic concentration in the household tube well (≥100 ppb). In this double-blind study, one group will eat high-selenium lentils grown in western Canada; the other will consume low-selenium lentils grown in Idaho, USA. Each participant will consume 65 g of lentils each day for 6 months. At the onset, midterm, and end of the trial, blood, urine and stool, plus hair (day 1 and at 6 months only) samples will be collected and a health examination conducted including assessment of acute lung inflammation, body mass and height, and blood pressure. The major outcome will be arsenic excretion in urine and feces, as well as arsenic deposition in hair and morbidity outcomes as assessed by a biweekly questionnaire. Secondary outcomes include antioxidant status, lipid profile, lung inflammation status, and blood pressure. Selenium pills as a treatment for arsenic exposure are costly and inconvenient, whereas a whole food approach to lower the toxic burden of arsenic may be a practical remedy for Bangladeshi people while efforts to provide safe drinking water are continuing. If high-selenium lentils prove to be effective in counteracting arsenic toxicity, agronomic partnerships between Canada and Bangladesh will work to improve the selenium content of the Bangladeshi-grown lentil crops. Results will be presented to the community to promote informed food choices, which may include increasing selenium in their diet. ClinicalTrials.gov NCT02429921.

Alterations of urinary metabolite profile in model diabetic nephropathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stec, Donald F.; Wang, Suwan; Stothers, Cody

2015-01-09

Highlights: • {sup 1}H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelialmore » nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be useful new tools in metabolomic studies relevant to human pathology.« less

Transcriptomic Responses During Early Development Following Arsenic Exposure in Western Clawed Frogs, Silurana tropicalis.

PubMed

Zhang, Jing; Koch, Iris; Gibson, Laura A; Loughery, Jennifer R; Martyniuk, Christopher J; Button, Mark; Caumette, Guilhem; Reimer, Kenneth J; Cullen, William R; Langlois, Valerie S

2015-12-01

Arsenic compounds are widespread environmental contaminants and exposure elicits serious health issues, including early developmental anomalies. Depending on the oxidation state, the intermediates of arsenic metabolism interfere with a range of subcellular events, but the fundamental molecular events that lead to speciation-dependent arsenic toxicity are not fully elucidated. This study therefore assesses the impact of arsenic exposure on early development by measuring speciation and gene expression profiles in the developing Western clawed frog (Silurana tropicalis) larvae following the environmental relevant 0.5 and 1 ppm arsenate exposure. Using HPLC-ICP-MS, arsenate, dimethylarsenic acid, arsenobetaine, arsenocholine, and tetramethylarsonium ion were detected. Microarray and pathway analyses were utilized to characterize the comprehensive transcriptomic responses to arsenic exposure. Clustering analysis of expression data showed distinct gene expression patterns in arsenate treated groups when compared with the control. Pathway enrichment revealed common biological themes enriched in both treatments, including cell signal transduction, cell survival, and developmental pathways. Moreover, the 0.5 ppm exposure led to the enrichment of pathways and biological processes involved in arsenic intake or efflux, as well as histone remodeling. These compensatory responses are hypothesized to be responsible for maintaining an in-body arsenic level comparable to control animals. With no appreciable changes observed in malformation and mortality between control and exposed larvae, this is the first study to suggest that the underlying transcriptomic regulations related to signal transduction, cell survival, developmental pathways, and histone remodeling may contribute to maintaining ongoing development while coping with the potential arsenic toxicity in S. tropicalis during early development. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Metal mixtures in urban and rural populations in the US: The Multi-Ethnic Study of Atherosclerosis and the Strong Heart Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pang, Yuanjie, E-mail: yuanjie.p@gmail.com

Background: Natural and anthropogenic sources of metal exposure differ for urban and rural residents. We searched to identify patterns of metal mixtures which could suggest common environmental sources and/or metabolic pathways of different urinary metals, and compared metal-mixtures in two population-based studies from urban/sub-urban and rural/town areas in the US: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Strong Heart Study (SHS). Methods: We studied a random sample of 308 White, Black, Chinese-American, and Hispanic participants in MESA (2000–2002) and 277 American Indian participants in SHS (1998–2003). We used principal component analysis (PCA), cluster analysis (CA), and linear discriminant analysismore » (LDA) to evaluate nine urinary metals (antimony [Sb], arsenic [As], cadmium [Cd], lead [Pb], molybdenum [Mo], selenium [Se], tungsten [W], uranium [U] and zinc [Zn]). For arsenic, we used the sum of inorganic and methylated species (∑As). Results: All nine urinary metals were higher in SHS compared to MESA participants. PCA and CA revealed the same patterns in SHS, suggesting 4 distinct principal components (PC) or clusters (∑As-U-W, Pb-Sb, Cd-Zn, Mo-Se). In MESA, CA showed 2 large clusters (∑As-Mo-Sb-U-W, Cd-Pb-Se-Zn), while PCA showed 4 PCs (Sb-U-W, Pb-Se-Zn, Cd-Mo, ∑As). LDA indicated that ∑As, U, W, and Zn were the most discriminant variables distinguishing MESA and SHS participants. Conclusions: In SHS, the ∑As-U-W cluster and PC might reflect groundwater contamination in rural areas, and the Cd-Zn cluster and PC could reflect common sources from meat products or metabolic interactions. Among the metals assayed, ∑As, U, W and Zn differed the most between MESA and SHS, possibly reflecting disproportionate exposure from drinking water and perhaps food in rural Native communities compared to urban communities around the US. - Highlights: • We identified and compared environmental sources of urinary metals in MESA and SHS. • ∑As-U-W in SHS may reflect groundwater contamination in rural areas. • Cd-Zn in SHS may reflect common sources from meat products or metabolic interaction. • ∑As, U, W, and Zn differed the most between MESA and SHS participants.« less

DOES RESPONSE EVALUATION OF GENE EXPRESSION PROFILES IN THE SKIN OF K6/ODC MICE EXPOSED TO SODIUM ARSENITE

EPA Science Inventory

Abstract - Chronic drinking water exposure to inorganic arsenic and its metabolites increases tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, gene expression profiles were characterized fro...

Local Resistance Profiling of Ultra-Shallow Junction with Spike Lamp and Laser Annealing Using Scanning Spreading Resistance Microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abo, Satoshi; Tanaka, Yuji; Nishikawa, Kazuhisa

2008-11-03

Local resistance profiles of ultra-shallow arsenic implanted into silicon with an energy of 3.5 keV and a dose of 1.2x10{sup 15} ions/cm{sup 2} activated by conventional spike lamp and laser annealing were measured by SSRM in a nitrogen atmosphere with a depth resolution of less than 10 nm for investigating the combination of the conventional spike lamp and laser annealing. Spike lamp annealing at 1050 deg. C followed by laser annealing at a power density of 0.42 kW/mm{sup 2} was found to give the lowest sheet resistance. The resistance profiles obtained by SSRM also indicated the lowest resistance for themore » sample after spike lamp annealing at 1050 deg. C followed by laser annealing with a power density of 0.42 kW/mm{sup 2}. Laser annealing alone with a power density of 0.42 kW/mm{sup 2} resulted in the higher sheet resistance, though the shallower resistance profile could be obtained. Spike lamp annealing followed by laser annealing procedures are effective in activating shallow arsenic profiles.« less

Clinical implications of the microbiome in urinary tract diseases.

PubMed

Hiergeist, Andreas; Gessner, André

2017-03-01

The purpose of this review is to outline and evaluate the most recent literature on the role of the microbiome in urinary tract diseases. High throughput molecular DNA sequencing of bacterial 16S rRNA genes enabled the analysis of complex microbial communities inhabiting the human urinary tract. Several recent studies have identified bacterial taxa of the urinary microbiome to impact urinary tract diseases including interstitial cystitis, urgency urinary incontinence or calcium oxalate stone formation. Furthermore, treatment of urinary tract infections by antibiotics globally impacts community profiles of the intestinal microbiota and might indirectly influence human health. Alternative treatment options like application of probiotics for the treatment of urinary tract infections are currently under investigation. The urinary microbiome and its relationship to urinary tract diseases is currently under comprehensive investigation. Further studies are needed to shed light on the role of commensal microbiota for urinary tract infections.

Postnatal arsenic exposure and attention impairment in school children.

PubMed

Rodríguez-Barranco, Miguel; Gil, Fernando; Hernández, Antonio F; Alguacil, Juan; Lorca, Andres; Mendoza, Ramón; Gómez, Inmaculada; Molina-Villalba, Isabel; González-Alzaga, Beatriz; Aguilar-Garduño, Clemente; Rohlman, Diane S; Lacasaña, Marina

2016-01-01

Over the last few decades there has been an increased concern about the health risks from exposure to metallic trace elements, including arsenic, because of their potential neurotoxic effects on the developing brain. This study assessed whether urinary arsenic (UA) levels are associated with attention performance and Attention-Deficit/Hyperactivity Disorder (ADHD) in children living in an area with high industrial and mining activities in Southwestern Spain. A cross-sectional study was conducted on 261 children aged 6-9 years. Arsenic levels were determined in urine samples. Attention was measured by using 4 independent tools: a) tests from the Behavioral Assessment and Research System (BARS) designed to measure attention function: Simple Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT); b) AULA Test, a virtual reality (VR)-based test that evaluates children's response to several stimuli in an environment simulating a classroom; c) Child Behavior Checklist (CBCL), administered to parents; and d) Teacher's Report Form (TRF), administered to teachers. Multivariate linear and logistic regression models, adjusted for potential confounders, were used to estimate the magnitude of the association between UA levels and attention performance scores. Higher UA levels were associated with an increased latency of response in RTT (β = 12.3; 95% confidence interval (CI): 3.5-21.1) and SAT (β = 3.6; 95% CI: .4-6.8) as well as with worse performance on selective and focalized attention in the AULA test (β for impulsivity = .6; 95% CI: .1-1.1; β for inattention = .5; 95% CI: .03-1.0). A dose-response relationship was observed between UA levels and inattention and impulsivity scores. In contrast, results from the CBCL and TRF tests failed to show a significant association with UA levels. In conclusion, UA levels were associated with impaired attention/cognitive function, even at levels considered safe. These results provide additional evidence that postnatal arsenic exposure impairs neurological function in children. Copyright © 2015 Elsevier Ltd. All rights reserved.

A cluster-based randomized controlled trial promoting community participation in arsenic mitigation efforts in Bangladesh.

PubMed

George, Christine Marie; van Geen, Alexander; Slavkovich, Vesna; Singha, Ashit; Levy, Diane; Islam, Tariqul; Ahmed, Kazi Matin; Moon-Howard, Joyce; Tarozzi, Alessandro; Liu, Xinhua; Factor-Litvak, Pam; Graziano, Joseph

2012-06-19

To reduce arsenic (As) exposure, we evaluated the effectiveness of training community members to perform water arsenic (WAs) testing and provide As education compared to sending representatives from outside communities to conduct these tasks. We conducted a cluster based randomized controlled trial of 20 villages in Singair, Bangladesh. Fifty eligible respondents were randomly selected in each village. In 10 villages, a community member provided As education and WAs testing. In a second set of 10 villages an outside representative performed these tasks. Overall, 53% of respondents using As contaminated wells, relative to the Bangladesh As standard of 50 μg/L, at baseline switched after receiving the intervention. Further, when there was less than 60% arsenic contaminated wells in a village, the classification used by the Bangladeshi and UNICEF, 74% of study households in the community tester villages, and 72% of households in the outside tester villages reported switching to an As safe drinking water source. Switching was more common in the outside-tester (63%) versus community-tester villages (44%). However, after adjusting for the availability of arsenic safe drinking water sources, well switching did not differ significantly by type of As tester (Odds ratio = 0.86[95% confidence interval 0.42-1.77). At follow-up, among those using As contaminated wells who switched to safe wells, average urinary As concentrations significantly decreased. The overall intervention was effective in reducing As exposure provided there were As-safe drinking water sources available. However, there was not a significant difference observed in the ability of the community and outside testers to encourage study households to use As-safe water sources. The findings of this study suggest that As education and WAs testing programs provided by As testers, irrespective of their residence, could be used as an effective, low cost approach to reduce As exposure in many As-affected areas of Bangladesh.

Whey versus soy protein diets and renal status in rats.

PubMed

Aparicio, Virginia A; Nebot, Elena; Tassi, Mohamed; Camiletti-Moirón, Daniel; Sanchez-Gonzalez, Cristina; Porres, Jesús M; Aranda, Pilar

2014-09-01

Different dietary protein sources can promote different renal statuses. We examined the effects of whey protein (WP) and soy protein (SP) intake on plasma, urinary, and morphological renal parameters in rats. One hundred and twenty Wistar rats were randomly distributed into 2 experimental groups fed with either WP or SP diets over 12 weeks. These diets were based on commercial WP or SP isolates. The urinary calcium content was higher in the WP diet compared to the SP diet group (P<.001) whereas the urinary citrate level was lower (P<.001). The urinary pH was more acidic in the WP diet group compared to the SP diet group (P<.001); however, no differences were observed between the groups for any of the renal morphological parameters analyzed (all, P>.05) or other plasma renal markers such as albumin or urea concentrations. The increase of acid and urinary calcium and the lower urinary citrate level observed in the WP diet group could increase the incidence of nephrolithiasis compared to the SP diet group. Despite the WP showed poorer acid-base profile, no significant morphological renal changes were observed. These results suggest that the use of SP instead of WP appears to promote a more alkaline plasma and urinary profile, with their consequent renal advantages.

Urinary profiles of luteinizing hormone, estrogen and progestagen during the estrous and gestational periods in giant pandas (Ailuropda melanoleuca).

PubMed

Cai, Kailai; Yie, Shangmian; Zhang, Zhihe; Wang, Juan; Cai, Zhigang; Luo, Li; Liu, Yuliang; Wang, Hairui; Huang, He; Wang, Chengdong; Huang, Xiangming; Lan, Jingchao; Hou, Rong

2017-01-16

Luteinizing hormone (LH) is one of the main pituitary hormones that regulate ovulation, however its role has not been studied in giant panda. In this study, we developed an ELISA method for the detection of panda urinary LH. We analyzed urinary hormones of 24 female pandas during 36 breeding periods, we found females could easily be impregnated if the first mating occurred within 10 hours after LH peak. We also found the patterns of the ratios of urinary LH and progestagen in pandas that bred and successfully gave birth were significantly different from those that bred but failed to give birth. These data was the first to provide the urinary LH profiles during the estrous and gestational periods in pandas, and demonstrated that the appearance of the urinary LH peak indicated the timing of ovulation. The LH detection together with estrogen analysis makes the window for successful mating narrower than previously reported. Moreover, detection of urinary LH and progestagen can be used to discriminate between pregnancies and pseudopregnancies/miscarriages in the species. Thus, our findings suggest that LH not only plays a critical role in regulating ovulation but also plays an important role in maintaining pregnancy in the giant panda.

Urinary profiles of luteinizing hormone, estrogen and progestagen during the estrous and gestational periods in giant pandas (Ailuropda melanoleuca)

PubMed Central

Cai, Kailai; Yie, Shangmian; Zhang, Zhihe; Wang, Juan; Cai, Zhigang; Luo, Li; Liu, Yuliang; Wang, Hairui; Huang, He; Wang, Chengdong; Huang, Xiangming; Lan, Jingchao; Hou, Rong

2017-01-01

Luteinizing hormone (LH) is one of the main pituitary hormones that regulate ovulation, however its role has not been studied in giant panda. In this study, we developed an ELISA method for the detection of panda urinary LH. We analyzed urinary hormones of 24 female pandas during 36 breeding periods, we found females could easily be impregnated if the first mating occurred within 10 hours after LH peak. We also found the patterns of the ratios of urinary LH and progestagen in pandas that bred and successfully gave birth were significantly different from those that bred but failed to give birth. These data was the first to provide the urinary LH profiles during the estrous and gestational periods in pandas, and demonstrated that the appearance of the urinary LH peak indicated the timing of ovulation. The LH detection together with estrogen analysis makes the window for successful mating narrower than previously reported. Moreover, detection of urinary LH and progestagen can be used to discriminate between pregnancies and pseudopregnancies/miscarriages in the species. Thus, our findings suggest that LH not only plays a critical role in regulating ovulation but also plays an important role in maintaining pregnancy in the giant panda. PMID:28091600

In utero and early childhood exposure to arsenic decreases lung function in children.

PubMed

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Gandolfi, A Jay; Gonzalez-De Alba, Cesar

2015-04-01

The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

Phytoremediation: novel approaches to cleaning up polluted soils.

PubMed

Krämer, Ute

2005-04-01

Environmental pollution with metals and xenobiotics is a global problem, and the development of phytoremediation technologies for the plant-based clean-up of contaminated soils is therefore of significant interest. Phytoremediation technologies are currently available for only a small subset of pollution problems, such as arsenic. Arsenic removal employs naturally selected hyperaccumulator ferns, which accumulate very high concentrations of arsenic specifically in above-ground tissues. Elegant two-gene transgenic approaches have been designed for the development of mercury or arsenic phytoremediation technologies. In a plant that naturally hyperaccumulates zinc in leaves, approximately ten key metal homeostasis genes are expressed at very high levels. This outlines the extent of change in gene activities needed in the engineering of transgenic plants for soil clean-up. Further analysis and discovery of genes for phytoremediation will benefit from the recent development of segregating populations for a genetic analysis of naturally selected metal hyperaccumulation in plants, and from comprehensive ionomics data--multi-element concentration profiles from a large number of Arabidopsis mutants.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meharg, A.A.; Shore, R.F.; Broadgate, K.

The toxicity and accumulation of arsenate was determined in the earthworm Lumbricus terrestris in soil from different layers of a forest profile. Toxicity increased fourfold between 2 and 10 d. Edaphic factors (pH, soil organic matter, and depth in soil profile) also affected toxicity with a three fold decrease in the concentration that causes 50% mortality with increasing depth in soil. In a 4-d exposure study, there was no evidence of arsenic bioconcentration in earthworm tissue, although bioaccumulation was occurring. There was a considerable difference in tissue residues between living and dead earthworms, with dead worms having higher concentrations. Thismore » difference was dependent on both soil arsenate concentration and on soil type. Over a wide range of soil arsenate concentrations, earthworm arsenic residues are homeostatically maintained in living worms, but this homeostasis breaks down during death. Alternatively, equilibration with soil residues may occur via accumulation after death. In long-term accumulation studies in soils dosed with a sublethal arsenate concentration, bioconcentration of arsenate did not occur until day 12, after which earthworm concentrations rose steadily above the soil concentration, with residues in worms three fold higher than soil concentrations by the termination of the study. This bioconcentration only occurred in depurated worms over the time period of the study. Initially, depurated worms had lower arsenic concentrations than undepurated until tissue concentrations were equivalent to the soil concentration. Once tissue concentration was greater than soil concentration, depurated worms had higher arsenic residues than undepurated.« less

GENE EXPRESSION PROFILING OF MOUSE SKIN AND PAPILLOMAS FOLLOWING CHRONIC EXPOSURE TO MONOMETHYLARSONOUS ACID IN K6/ODC TRANSGENIC MICE

EPA Science Inventory

Methylarsonous acid [MMA(III)], a common metabolite of inorganic arsenic metabolism, increases tumor frequency in the skin of K6/ODC transgenic mice following a chronic exposure. To characterize gene expression profiles predictive of MMA(III) exposure and mode of action of carcin...

Roxarsone, inorganic arsenic, and other arsenic species in chicken: a U.S.-based market basket sample.

PubMed

Nachman, Keeve E; Baron, Patrick A; Raber, Georg; Francesconi, Kevin A; Navas-Acien, Ana; Love, David C

2013-07-01

Inorganic arsenic (iAs) causes cancer and possibly other adverse health outcomes. Arsenic-based drugs are permitted in poultry production; however, the contribution of chicken consumption to iAs intake is unknown. We sought to characterize the arsenic species profile in chicken meat and estimate bladder and lung cancer risk associated with consuming chicken produced with arsenic-based drugs. Conventional, antibiotic-free, and organic chicken samples were collected from grocery stores in 10 U.S. metropolitan areas from December 2010 through June 2011. We tested 116 raw and 142 cooked chicken samples for total arsenic, and we determined arsenic species in 65 raw and 78 cooked samples that contained total arsenic at ≥ 10 µg/kg dry weight. The geometric mean (GM) of total arsenic in cooked chicken meat samples was 3.0 µg/kg (95% CI: 2.5, 3.6). Among the 78 cooked samples that were speciated, iAs concentrations were higher in conventional samples (GM = 1.8 µg/kg; 95% CI: 1.4, 2.3) than in antibiotic-free (GM = 0.7 µg/kg; 95% CI: 0.5, 1.0) or organic (GM = 0.6 µg/kg; 95% CI: 0.5, 0.8) samples. Roxarsone was detected in 20 of 40 conventional samples, 1 of 13 antibiotic-free samples, and none of the 25 organic samples. iAs concentrations in roxarsone-positive samples (GM = 2.3 µg/kg; 95% CI: 1.7, 3.1) were significantly higher than those in roxarsone-negative samples (GM = 0.8 µg/kg; 95% CI: 0.7, 1.0). Cooking increased iAs and decreased roxarsone concentrations. We estimated that consumers of conventional chicken would ingest an additional 0.11 µg/day iAs (in an 82-g serving) compared with consumers of organic chicken. Assuming lifetime exposure and a proposed cancer slope factor of 25.7 per milligram per kilogram of body weight per day, this increase in arsenic exposure could result in 3.7 additional lifetime bladder and lung cancer cases per 100,000 exposed persons. Conventional chicken meat had higher iAs concentrations than did conventional antibiotic-free and organic chicken meat samples. Cessation of arsenical drug use could reduce exposure and the burden of arsenic-related disease in chicken consumers.

Roxarsone, Inorganic Arsenic, and Other Arsenic Species in Chicken: A U.S.-Based Market Basket Sample

PubMed Central

Baron, Patrick A.; Raber, Georg; Francesconi, Kevin A.; Navas-Acien, Ana; Love, David C.

2013-01-01

Background: Inorganic arsenic (iAs) causes cancer and possibly other adverse health outcomes. Arsenic-based drugs are permitted in poultry production; however, the contribution of chicken consumption to iAs intake is unknown. Objectives: We sought to characterize the arsenic species profile in chicken meat and estimate bladder and lung cancer risk associated with consuming chicken produced with arsenic-based drugs. Methods: Conventional, antibiotic-free, and organic chicken samples were collected from grocery stores in 10 U.S. metropolitan areas from December 2010 through June 2011. We tested 116 raw and 142 cooked chicken samples for total arsenic, and we determined arsenic species in 65 raw and 78 cooked samples that contained total arsenic at ≥ 10 µg/kg dry weight. Results: The geometric mean (GM) of total arsenic in cooked chicken meat samples was 3.0 µg/kg (95% CI: 2.5, 3.6). Among the 78 cooked samples that were speciated, iAs concentrations were higher in conventional samples (GM = 1.8 µg/kg; 95% CI: 1.4, 2.3) than in antibiotic-free (GM = 0.7 µg/kg; 95% CI: 0.5, 1.0) or organic (GM = 0.6 µg/kg; 95% CI: 0.5, 0.8) samples. Roxarsone was detected in 20 of 40 conventional samples, 1 of 13 antibiotic-free samples, and none of the 25 organic samples. iAs concentrations in roxarsone-positive samples (GM = 2.3 µg/kg; 95% CI: 1.7, 3.1) were significantly higher than those in roxarsone-negative samples (GM = 0.8 µg/kg; 95% CI: 0.7, 1.0). Cooking increased iAs and decreased roxarsone concentrations. We estimated that consumers of conventional chicken would ingest an additional 0.11 µg/day iAs (in an 82-g serving) compared with consumers of organic chicken. Assuming lifetime exposure and a proposed cancer slope factor of 25.7 per milligram per kilogram of body weight per day, this increase in arsenic exposure could result in 3.7 additional lifetime bladder and lung cancer cases per 100,000 exposed persons. Conclusions: Conventional chicken meat had higher iAs concentrations than did conventional antibiotic-free and organic chicken meat samples. Cessation of arsenical drug use could reduce exposure and the burden of arsenic-related disease in chicken consumers. PMID:23694900

Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fuse, Yuji; Nguyen, Vu Thanh; Kobayashi, Makoto, E

Transcription factor Nrf2 induces a number of detoxifying enzymes and antioxidant proteins to confer protection against the toxic effects of a diverse range of chemicals including inorganic arsenicals. Although a number of studies using cultured cells have demonstrated that Nrf2 has a cell-protective function against acute and high-dose arsenic toxicity, there is no clear in vivo evidence of this effect. In the present study, we genetically investigated the protective role of Nrf2 against acute sodium arsenite toxicity using the zebrafish Nrf2 mutant, nrf2a{sup fh318}. After treatment with 1 mM sodium arsenite, the survival of nrf2a{sup fh318} larvae was significantly shortermore » than that of wild-type siblings, suggesting that Nrf2 protected the zebrafish larvae against high-dose arsenite exposure. To understand the molecular basis of the Nrf2-dependent protection, we analyzed the gene expression profiles after arsenite exposure, and found that the genes involved in the antioxidative function (prdx1 and gclc), arsenic metabolism (gstp1) and xenobiotic elimination (abcc2) were induced in an Nrf2-dependent manner. Furthermore, pre-treatment with sulforaphane, a well-known Nrf2 activator improved the survival of zebrafish larvae after arsenic exposure. Based on these results, we concluded that Nrf2 plays a fundamental and conserved role in protection against acute sodium arsenite toxicity. - Highlights: • The role of Nrf2 under arsenite exposure was valuated using zebrafish. • Nrf2 mutant zebrafish was highly sensitive to acute arsenic toxicity. • Nrf2 induced anti-arsenic genes in response to arsenite. • Sulforaphane attenuated arsenic toxicity through Nrf2 activation. • Nrf2 system plays an important role in the defense against acute arsenic toxicity.« less

High resolution profile of inorganic aqueous geochemistry and key redox zones in an arsenic bearing aquifer in Cambodia.

PubMed

Richards, Laura A; Magnone, Daniel; Sovann, Chansopheaktra; Kong, Chivuth; Uhlemann, Sebastian; Kuras, Oliver; van Dongen, Bart E; Ballentine, Christopher J; Polya, David A

2017-07-15

Arsenic contamination of groundwaters in South and Southeast Asia is a major threat to public health. In order to better understand the geochemical controls on the mobility of arsenic in a heavily arsenic-affected aquifer in northern Kandal Province, Cambodia, key changes in inorganic aqueous geochemistry have been monitored at high vertical and lateral resolution along dominant groundwater flow paths along two distinct transects. The two transects are characterized by differing geochemical, hydrological and lithological conditions. Arsenic concentrations in groundwater are highly heterogenous, and are broadly positively associated with iron and negatively associated with sulfate and dissolved oxygen. The observed correlations are generally consistent with arsenic mobilization by reductive-dissolution of iron (hydr)oxides. Key redox zones, as identified using groupings of the PHREEQC model equilibrium electron activity of major redox couples (notably ammonium/nitrite; ammonium/nitrate; nitrite/nitrate; dissolved oxygen/water) have been identified and vary with depth, site and season. Mineral saturation is also characterized. Seasonal changes in groundwater chemistry were observed in areas which were (i) sandy and of high permeability; (ii) in close proximity to rivers; and/or (iii) in close proximity to ponds. Such changes are attributed to monsoonal-driven surface-groundwater interactions and are consistent with the separate provenance of recharge sources as identified using stable isotope mixing models. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Maternal arsenic exposure and gestational diabetes and glucose intolerance in the New Hampshire birth cohort study.

PubMed

Farzan, Shohreh F; Gossai, Anala; Chen, Yu; Chasan-Taber, Lisa; Baker, Emily; Karagas, Margaret

2016-11-08

Gestational diabetes mellitus (GDM) is a major pregnancy complication with detrimental effects for both mothers and their children. Accumulating evidence has suggested a potential role for arsenic (As) exposure in the development of GDM, but current studies have not assessed As exposure from water, urine or toenail samples. We investigated the association between As exposure and risk of glucose intolerance and GDM among 1151 women enrolled in the New Hampshire Birth Cohort Study. Arsenic was measured in home well water and via biomarkers (i.e., maternal urine collected ~24-28 weeks gestation and toenail clippings collected 2 weeks postpartum). A total of 105 (9.1 %) of women were diagnosed with glucose intolerance and 14 (1.2 %) of women were diagnosed with GDM. A total of 10.3 % of women had water As levels above 10 μg/L, with a mean As level of 4.2. Each 5 μg/L increase in As concentration in home well water was associated with a ~10 % increased odds of GDM (OR: 1.1, 95 % CI 1.0, 1.2). A positive and statistically significant association also was observed between toenail As and GDM (OR: 4.5, 95 % CI 1.2, 16.6), but not urinary arsenic (OR: 0.8, 95 % CI 0.3, 2.4). In a stratified analysis, the association between water As and GDM and glucose intolerance was largely limited to obese women (OR: 1.7, 95 % CI 1.0, 2.8). Our findings support the role of As exposure via water from private wells in the incidence of GDM and that this association may be modified by body composition.

Arsenic-containing fatty acids and hydrocarbons in marine oils - determination using reversed-phase HPLC-ICP-MS and HPLC-qTOF-MS.

PubMed

Sele, Veronika; Sloth, Jens J; Holmelid, Bjarte; Valdersnes, Stig; Skov, Kasper; Amlund, Heidi

2014-04-01

Arsenolipids are the major arsenic species present in marine oils. Several structures of arsenolipids have been elucidated the last 5 years, demonstrating the chemical complexity of this trace element in the marine environment. Several commercial fish oils and marine oils, ranging in total arsenic concentrations from 1.6 to 12.5 mg kg(-1) oil, were analyzed for arsenolipids using reversed-phase high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The arsenolipids were quantified using three different arsenic-containing calibration standards; dimethylarsinate (DMA), triphenylarsinoxide (Ph₃AsO) and a synthesized arsenic-containing hydrocarbon (AsHC) (dimethylarsinoyl nonadecane; C₂₁H₄₃AsO). The observed variation in signal intensity for arsenic during the gradient elution profile in reversed-phase HPLC was compensated for by determining the time-resolved response factors for the arsenolipids. Isotopes of germanium ((74)Ge) and indium ((115)In) were suited as internal standards for arsenic, and were used for verification of the arsenic signal response factors during the gradient elution. Dimethylarsinate was the most suitable calibration standard for the quantification of arsenolipids, with recoveries between 91% and 104% compared to total arsenic measurements in the same extracts. A range of marine oils was investigated, including oils of several fish species, cod liver and seal, as well as three commercial fish oils. The AsHCs - C₁₇H₃₈AsO, C₁₉H₄₂AsO and C₂₃H₃₈AsO - were identified as the major arsenolipids in the extracts of all oils by HPLC coupled with quadrupole time-of-flight mass spectrometry (qTOF-MS). Minor amounts of two arsenic-containing fatty acids (AsFAs) (C₂₃H₃₈AsO₃ and C₂₄H₃₈AsO₃) were also detected in the oils. The sum of the AsHCs and the AsFAs determined in the present study accounted for 17-42% of the total arsenic in the oils. Copyright © 2014 Elsevier B.V. All rights reserved.

Gender and age differences in mixed metal exposure and urinary excretion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berglund, Marika, E-mail: Marika.Berglund@ki.se; Lindberg, Anna-Lena; Rahman, Mahfuzar

Background: Little is known about the variation in exposure to toxic metals by age and gender and other potential modifying factors. We evaluated age and gender differences by measurements of metal/element concentrations in urine in a rural population in Matlab, Bangladesh, in three age groups: 8-12 (N=238), 14-15 (N=107) and 30-88 (N=710) years of age, living in an area with no point sources of metal exposure but where elevated water arsenic concentrations are prevalent. Results: We found marked differences in urine concentrations of metals and trace elements by gender, age, tobacco use, socioeconomic and nutritional status. Besides a clearly elevatedmore » urinary arsenic concentration in all age groups (medians 63-85 {mu}g As/L), and despite the low degree of contamination from industries and traffic, the urine concentrations of toxic metals such as cadmium and lead were clearly elevated, especially in children (median 0.31 {mu}g Cd/L and 2.9 {mu}g Pb/L, respectively). In general, women had higher urinary concentrations of toxic metals, especially Cd (median 0.81 {mu}g/L) compared to men (0.66 {mu}g/L) and U (median 10 ng/L in women, compared to 6.4 ng/L in men), while men had higher urinary concentrations of the basic and essential elements Ca (69 mg/L in men, 30-50 years, compared to 52 mg/L in women), Mg (58 mg/L in men compared to 50 mg/L in women), Zn (182 {mu}g/L in men compared to 117 {mu}g/L in women) and Se (9.9 {mu}g/L in men compared to 8.7 {mu}g/L in women). Manganese was consistently higher in females than in males in all age groups, suggesting a biological difference between females and males in Mn metabolism. Increasing socioeconomic status decreased the toxic metal exposure significantly in children and especially in men. Poor iron status was detected in 17% of children, adolescents and women, but only in 6% of men. Also zinc deficiency was more prevalent in females than in males. Conclusions: Women and children seemed to be more at risk for toxic metal exposure than men and at the same time more vulnerable to micronutrient deficiency. Higher concentrations of the toxic metals in urine in women are likely to reflect an increased gastrointestinal absorption of these metals at micronutrient deficiency, such as low body iron stores and Zn deficiency. Higher urinary concentrations of the essential elements in men likely reflect a better nutritional status. There is a need for information on exposure, lifestyle and socioeconomic factors, stratified by gender and age, for the purpose of conducting balanced risk assessment and management that considers such differences.« less

Prenatal arsenic exposure and the epigenome: altered microRNAs associated with innate and adaptive immune signaling in newborn cord blood

PubMed Central

Rager, Julia E.; Bailey, Kathryn A.; Smeester, Lisa; Miller, Sloane K.; Parker, Joel S.; Laine, Jessica E.; Drobná, Zuzana; Currier, Jenna; Douillet, Christelle; Olshan, Andrew F.; Rubio-Andrade, Marisela; Stýblo, Miroslav; García-Vargas, Gonzalo; Fry, Rebecca C.

2014-01-01

The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In the present study, we examined a subset (n=40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 μg/L (mean=51.7 μg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 μg/L (mean=64.5 μg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. PMID:24327377

Metabolic profiling in Maturity-onset diabetes of the young (MODY) and young onset type 2 diabetes fails to detect robust urinary biomarkers.

PubMed

Gloyn, Anna L; Faber, Johan H; Malmodin, Daniel; Thanabalasingham, Gaya; Lam, Francis; Ueland, Per Magne; McCarthy, Mark I; Owen, Katharine R; Baunsgaard, Dorrit

2012-01-01

It is important to identify patients with Maturity-onset diabetes of the young (MODY) as a molecular diagnosis determines both treatment and prognosis. Genetic testing is currently expensive and many patients are therefore not assessed and are misclassified as having either type 1 or type 2 diabetes. Biomarkers could facilitate the prioritisation of patients for genetic testing. We hypothesised that patients with different underlying genetic aetiologies for their diabetes could have distinct metabolic profiles which may uncover novel biomarkers. The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK) or hepatocyte nuclear factor 1 alpha (HNF1A), type 2 diabetes (T2D) and normoglycaemic control subjects. Urinary metabolic profiling by Nuclear Magnetic Resonance (NMR) and ultra performance liquid chromatography hyphenated to Q-TOF mass spectrometry (UPLC-MS) was performed in a Discovery set of subjects with HNF1A-MODY (n = 14), GCK-MODY (n = 17), T2D (n = 14) and normoglycaemic controls (n = 34). Data were used to build a valid partial least squares discriminate analysis (PLS-DA) model where HNF1A-MODY subjects could be separated from the other diabetes subtypes. No single metabolite contributed significantly to the separation of the patient groups. However, betaine, valine, glycine and glucose were elevated in the urine of HNF1A-MODY subjects compared to the other subgroups. Direct measurements of urinary amino acids and betaine in an extended dataset did not support differences between patients groups. Elevated urinary glucose in HNF1A-MODY is consistent with the previously reported low renal threshold for glucose in this genetic subtype. In conclusion, we report the first metabolic profiling study in monogenic diabetes and show that, despite the distinct biochemical pathways affected, there are unlikely to be robust urinary biomarkers which distinguish monogenic subtypes from T2D. Our results have implications for studies investigating metabolic profiles in complex traits including T2D.

Genotoxicity surveillance programme in workers dismantling World War I chemical ammunition.

PubMed

Mateuca, R A; Carton, C; Roelants, M; Roesems, S; Lison, D; Kirsch-Volders, M

2010-06-01

To evaluate the effectiveness of personal protective measures in a dismantling plant for chemical weapons from World War I of the Belgian Defence. Seventeen NIOSH level B-equipped plant workers exposed to arsenic trichloride (AsCl(3)) in combination with phosgene or hydrogen cyanide (HCN) were compared to 24 NIOSH level C-protected field workers occasionally exposed to genotoxic chemicals (including AsCl(3)-phosgene/HCN) when collecting chemical ammunition, and 19 matched referents. Chromosomal aberrations (CA), micronuclei (MNCB and MNMC), sister chromatid exchanges (SCE) and high frequency cells (HFC) were analysed in peripheral blood lymphocytes. Urinary arsenic levels and genetic polymorphisms in major DNA repair enzymes (hOGG1(326), XRCC1(399), XRCC3(241)) were also assessed. SCE and HFC levels were significantly higher in plant-exposed versus referent subjects, but MNCB and MNMC were not different. MNCB, SCE and HFC levels were significantly higher and MNMC levels significantly lower in field-exposed workers versus referents. AsCl(3) exposure was not correlated with genotoxicity biomarkers. Protective measures for plant-exposed workers appear adequate, but protection for field-exposed individuals could be improved.

Biomarker Levels of Toxic Metals among Asian Populations in the United States: NHANES 2011-2012.

PubMed

Awata, Hiroshi; Linder, Stephen; Mitchell, Laura E; Delclos, George L

2017-03-01

The Centers for Disease Control and Prevention (CDC) recently found that Asians have considerably higher biomarker levels of cadmium, lead, mercury, and arsenic than whites, blacks, Mexican Americans, and other Hispanics in the United States. Our goal was to further evaluate the higher metal biomarker levels among Asians. Biomarker data (blood cadmium, blood lead, blood mercury, urinary total arsenic, and urinary dimethylarsinic acic) from individuals ≥ 6 years of age were obtained from the 2011-2012 National Health and Nutrition Examination Survey (NHANES). We compared geometric mean levels of these five metal biomarkers in Asians with those of four other NHANES race/ethnic groups (white, black, Mexican American, and other Hispanic), and across three Asian subgroups (Chinese, Asian Indian, and other Asian). We also evaluated associations between biomarker levels and sociodemographic, physical, dietary, and behavioral covariates across the Asian subgroups. Asians had significantly higher levels of all five metal biomarkers than other race/ethnic groups ( p < 0.05), regardless of sociodemographic, physical, dietary, behavioral, or geographic characteristics. We also found variations in biomarker levels across the Asian subgroups. In general, Asian Indians had lower levels than the other two Asian subgroups, except for blood lead. The following characteristics were found to be significant predictors of several biomarker levels: sex, age, education, birthplace, smoking, and fish consumption. Overall, the Asian group had the highest geometric mean biomarker levels for all of the five metal variables. Furthermore, we provided evidence that significant variations in the biomarker levels are present across the Asian subgroups in the United States. Citation: Awata H, Linder S, Mitchell LE, Delclos GL. 2017. Biomarker levels of toxic metals among Asian populations in the United States: NHANES 2011-2012. Environ Health Perspect 125:306-313; http://dx.doi.org/10.1289/EHP27.

Multiple Elemental Exposures Amongst Workers at the Agbogbloshie Electronic Waste (E-Waste) Site in Ghana

PubMed Central

Srigboh, Roland Kofi; Basu, Niladri; Stephens, Judith; Asampong, Emmanuel; Perkins, Marie; Neitzel, Richard L.; Fobil, Julius

2016-01-01

Electronic waste (e-waste) recycling is growing worldwide and raising a number of environmental health concerns. One of the largest e-waste sites is Agbogbloshie (Ghana). While several toxic elements have been reported in Agbogbloshie’s environment, there is limited knowledge of human exposures there. The objectives of this study were to characterize exposures to several essential (copper, iron, manganese, selenium, zinc) and toxic (arsenic, cadmium, cobalt, chromium, mercury, nickel, lead) elements in the urine and blood of male workers (n=58) at Agbogbloshie, as well as females (n=11) working in activities that serve the site, and to relate these exposures to sociodemographic and occupational characteristics. The median number of years worked at the site was 5, and the average worker indicated being active in 6.8 tasks (of 9 key e-waste job categories). Additionally, we categorized four main e-waste activities (in brackets % of population self-reported main activity): dealing (22.4%), sorting (24.1%), dismantling (50%), and burning (3.4%) e-waste materials. Many blood and urinary elements (including essential ones) were within biomonitoring reference ranges. However, blood cadmium (1.2 ug/L median) and lead (6.4 ug/dl; 67% above U.S. CDC/NIOSH reference level), and urinary arsenic (38.3 ug/L; 39% above U.S. ATSDR value) levels were elevated compared to background populations elsewhere. Workers who burned e-waste tended to have the highest biomarker levels. The findings of this study contribute to a growing body of work at Agbogbloshie (and elsewhere) to document that individuals working within e-waste sites are exposed to a number of toxic elements, some at potentially concerning levels. PMID:27580259

Multiple elemental exposures amongst workers at the Agbogbloshie electronic waste (e-waste) site in Ghana.

PubMed

Srigboh, Roland Kofi; Basu, Niladri; Stephens, Judith; Asampong, Emmanuel; Perkins, Marie; Neitzel, Richard L; Fobil, Julius

2016-12-01

Electronic waste (e-waste) recycling is growing worldwide and raising a number of environmental health concerns. One of the largest e-waste sites is Agbogbloshie (Ghana). While several toxic elements have been reported in Agbogbloshie's environment, there is limited knowledge of human exposures there. The objectives of this study were to characterize exposures to several essential (copper, iron, manganese, selenium, zinc) and toxic (arsenic, cadmium, cobalt, chromium, mercury, nickel, lead) elements in the urine and blood of male workers (n = 58) at Agbogbloshie, as well as females (n = 11) working in activities that serve the site, and to relate these exposures to sociodemographic and occupational characteristics. The median number of years worked at the site was 5, and the average worker indicated being active in 6.8 tasks (of 9 key e-waste job categories). Additionally, we categorized four main e-waste activities (in brackets % of population self-reported main activity): dealing (22.4%), sorting (24.1%), dismantling (50%), and burning (3.4%) e-waste materials. Many blood and urinary elements (including essential ones) were within biomonitoring reference ranges. However, blood cadmium (1.2 μg/L median) and lead (6.4 μg/dl; 67% above U.S. CDC/NIOSH reference level), and urinary arsenic (38.3 μg/L; 39% above U.S. ATSDR value) levels were elevated compared to background populations elsewhere. Workers who burned e-waste tended to have the highest biomarker levels. The findings of this study contribute to a growing body of work at Agbogbloshie (and elsewhere) to document that individuals working within e-waste sites are exposed to a number of toxic elements, some at potentially concerning levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Heavy metals exposures among Mexican farmworkers in eastern North Carolina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quandt, Sara A., E-mail: squandt@wfubmc.edu; Jones, Bradley T.; Talton, Jennifer W.

2010-01-15

Background: Immigrant farmworkers are a population at risk for numerous environmental and occupational exposures. The metals arsenic, lead, mercury, and cadmium are known neurotoxins to which workers can be exposed both in the US and in their country of origin. Because farmworkers are exposed to neurotoxic pesticides, they may be at risk for adverse health effects from the combined exposure. Objectives: To examine the relationship between exposure to metals, as measured in urine, with personal and work-related characteristics of Mexican migrant and seasonal farmworkers in the US. Methods: We analyzed data on metals found in urine of 258 farmworkers recruitedmore » from 44 camps in eastern North Carolina in 2007. Geometric means and 95% confidence intervals (CI) were used to compare data with data from the National Health and Nutrition Examination Survey (NHANES). We used multivariate regression models fitted for each metal to estimate the association of creatinine-corrected urinary metals and worker characteristics related to environmental and occupational exposures. Results: Geometric mean urinary metals concentrations ({mu}g/g creatinine) exceeded NHANES reference values for arsenic (13.23 [CI 11.11, 15.35] vs. 8.55 [CI 7.23, 9.86]) and lead (1.26 [CI 1.08, 1.43] vs. 0.63 [CI 0.60, 0.66]). Age, being from the central region of Mexico, and pack years of cigarette smoking were significant predictors of metals exposure; being a current smoker and years worked in US agriculture were not. Conclusions: This first study to examine indicators of worker body burdens of metals shows that workers have body burdens related to exposures other than work in the US. Further research should address their risk for adverse health outcomes due to combined exposures to neurotoxins in pesticides.« less

Urinary proteomic profiling in severe obesity and obstructive sleep apnoea with CPAP treatment

PubMed Central

Seetho, Ian W; Ramírez-Torres, Adela; Albalat, Amaya; Mullen, William; Mischak, Harald; Parker, Robert J; Craig, Sonya; Duffy, Nick; Hardy, Kevin J; Burniston, Jatin G; Wilding, John PH

2015-01-01

Introduction Obstructive sleep apnoea (OSA) is common in obesity and is associated with cardiovascular and metabolic complications. Continuous positive airway pressure (CPAP) in OSA may lead to physiological changes reflected in the urinary proteome. The aim of this study was to characterise the urinary proteome in severely obese adult subjects with OSA who were receiving CPAP compared with severely obese subjects without OSA. Methods Severely obese subjects with and without OSA were recruited. Subjects with OSA were receiving CPAP. Body composition and blood pressure measurements were recorded. Urinary samples were analysed by Capillary Electrophoresis–Mass Spectrometry (CE–MS). Results Twenty-seven subjects with OSA-on-CPAP (age 49±7years, BMI 43±7 kg/m2) and 25 controls without OSA (age 52±9years, BMI 39±4 kg/m2) were studied. Age and BMI were not significantly different between groups. Mean CPAP use for OSA patients was 14.5±1.0 months. Metabolic syndrome was present in 14(52%) of those with OSA compared with 6(24%) of controls (p=0.039). A urinary proteome comprising 15 peptides was identified showing differential expression between the groups (p<0.01). Although correction for multiple testing did not reach significance, sequences were determined for 8 peptides demonstrating origins from collagens, fibrinogen beta chain and T-cadherin that may be associated with underlying cardiovascular disease mechanisms in OSA. Conclusions The urinary proteome is compared in OSA with CPAP and without OSA in severe obesity. The effects of CPAP on OSA may lead to changes in the urinary peptides but further research work is needed to investigate the potential role for urinary proteomics in characterising urinary peptide profiles in OSA. PMID:26483946

Influence of fermentable carbohydrates or protein on large intestinal and urinary metabolomic profiles in piglets.

PubMed

Pieper, R; Neumann, K; Kröger, S; Richter, J F; Wang, J; Martin, L; Bindelle, J; Htoo, J K; Vahjen, V; Van Kessel, A G; Zentek, J

2012-12-01

It was recently shown that variations in the ratio of dietary fermentable carbohydrates (fCHO) and fermentable protein (fCP) differentially affect large intestinal microbial ecology and the mucosal response. Here we investigated the use of mass spectrometry to profile changes in metabolite composition in colon and urine associated with variation in dietary fCHO and fCP composition and mucosal physiology. Thirty-two weaned piglets were fed 4 diets in a 2 × 2 factorial design with low fCP and low fCHO, low fCP and high fCHO, high fCP and low fCHO, and high fCP and high fCHO. After 21 to 23 d, all pigs were euthanized and colon digesta and urine metabolite profiles were obtained by mass spectrometry. Analysis of mass spectra by partial least squares approach indicated a clustering of both colonic and urinary profiles for each pig by feeding group. Metabolite identification and annotation using the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed increased abundance of metabolites associated with arachidonic acid metabolism in colon of pigs fed a high concentration of fCP irrespective of dietary fCHO. Urinary metabolites did not show as clear patterns. Mass spectrometry can effectively differentiate metabolite profiles in colon contents and urine associated with changes in dietary composition. Whether metabolite profiling is an effective tool to identify specific metabolites (biomarkers) or metabolite profiles associated with gut function and integrity needs further elucidation.

[The profile urological emergencies at the Conakry University Teaching Hospital, Guinea].

PubMed

Bobo Diallo, A; Bah, I; Diallo, T M O; Bah, O R; Amougou, B; Bah, M D; Guirassy, S; Bobo Diallo, M

2010-03-01

To stick out the profile urological emergencies at the Conakry University Teaching Hospital, Guinea. This retrospective study, carried out over a period of 3 years (January 2005-December 2007), included 757 urological emergencies admitted to the urology department of the university hospital of Conakry, Guinea. The mean age of patients was 56 years. These patients had an age equal to or higher than 60 years in 58% of the cases. The sex ratio (M/F) was 16.6. According to the social profession, the farmer (40,6%) and workers (21%) were the dominant patients. The most frequent illness was vesical urinary retention (73.9%), hematuria (9.6%) and genito-urinary system trauma (7%). The most performed procedures were the installation of a urethral catheter (55.25%) and the installation of a suprapubic catheter (24.14%). The most frequent urological emergency in our country was vesical urinary retention, the hematuria and genito-urinary system trauma are not rare there. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults.

PubMed

Hall, Megan N; Howe, Caitlin G; Liu, Xinhua; Caudill, Marie A; Malysheva, Olga; Ilievski, Vesna; Lomax-Luu, Angela M; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad N; Islam, Tariqul; Graziano, Joseph H; Gamble, Mary V

2016-05-01

Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A better understanding of interactions between one-carbon metabolism intermediates may improve the ability to design nutrition interventions that further facilitate arsenic excretion. The objective was to determine if FA and/or creatine supplementation increase choline and betaine and decrease dimethylglycine (DMG). We conducted a secondary analysis of the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults (n = 605, aged 24-55 y, 50.3% male) who received arsenic-removal water filters. We examined treatment effects of FA and/or creatine supplementation on plasma choline, betaine, and DMG concentrations, measured by LC-tandem mass spectrometry at baseline and at week 12. Group comparisons were between 1) 400 and 800 μg FA/d (FA400 and FA800, respectively) compared with placebo, 2) creatine (3 g/d) compared with placebo, and 3) creatine plus FA400 compared with FA400. Choline decreased in the placebo group (-6.6%; 95% CI: -10.2%, -2.9%) but did not change in the FA groups (FA400: 2.5%; 95% CI: -0.9%, 6.1%; FA800: 1.4%; 95% CI: -2.5%, 5.5%; P < 0.05). Betaine did not change in the placebo group (-3.5%; 95% CI: -9.3%, 2.6%) but increased in the FA groups (FA400: 14.1%; 95% CI: 9.4%, 19.0%; FA800: 13.0%; 95% CI: 7.2%, 19.1%; P < 0.01). The decrease in DMG was greater in the FA groups (FA400: -26.7%; 95% CI: -30.9%, -22.2%; FA800: -27.8%; 95% CI: -31.8%, -23.4%) than in the placebo group (-12.3%; 95% CI: -18.1%, -6.2%; P < 0.01). The percentage change in choline, betaine, and DMG did not differ between creatine treatment arms and their respective reference groups. Supplementation for 12 wk with FA, but not creatine, increases plasma betaine, decreases plasma DMG, and prevents a decrease in plasma choline in arsenic-exposed Bangladeshi adults. This trial was registered at clinicaltrials.gov as NCT01050556. © 2016 American Society for Nutrition.

Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults123

PubMed Central

Hall, Megan N; Liu, Xinhua; Caudill, Marie A; Malysheva, Olga; Ilievski, Vesna; Lomax-Luu, Angela M; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad N; Islam, Tariqul; Graziano, Joseph H; Gamble, Mary V

2016-01-01

Background: Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A better understanding of interactions between one-carbon metabolism intermediates may improve the ability to design nutrition interventions that further facilitate arsenic excretion. Objective: The objective was to determine if FA and/or creatine supplementation increase choline and betaine and decrease dimethylglycine (DMG). Methods: We conducted a secondary analysis of the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults (n = 605, aged 24–55 y, 50.3% male) who received arsenic-removal water filters. We examined treatment effects of FA and/or creatine supplementation on plasma choline, betaine, and DMG concentrations, measured by LC–tandem mass spectrometry at baseline and at week 12. Group comparisons were between 1) 400 and 800 μg FA/d (FA400 and FA800, respectively) compared with placebo, 2) creatine (3 g/d) compared with placebo, and 3) creatine plus FA400 compared with FA400. Results: Choline decreased in the placebo group (−6.6%; 95% CI: −10.2%, −2.9%) but did not change in the FA groups (FA400: 2.5%; 95% CI: −0.9%, 6.1%; FA800: 1.4%; 95% CI: −2.5%, 5.5%; P < 0.05). Betaine did not change in the placebo group (−3.5%; 95% CI: −9.3%, 2.6%) but increased in the FA groups (FA400: 14.1%; 95% CI: 9.4%, 19.0%; FA800: 13.0%; 95% CI: 7.2%, 19.1%; P < 0.01). The decrease in DMG was greater in the FA groups (FA400: −26.7%; 95% CI: −30.9%, −22.2%; FA800: −27.8%; 95% CI: −31.8%, −23.4%) than in the placebo group (−12.3%; 95% CI: −18.1%, −6.2%; P < 0.01). The percentage change in choline, betaine, and DMG did not differ between creatine treatment arms and their respective reference groups. Conclusion: Supplementation for 12 wk with FA, but not creatine, increases plasma betaine, decreases plasma DMG, and prevents a decrease in plasma choline in arsenic-exposed Bangladeshi adults. This trial was registered at clinicaltrials.gov as NCT01050556. PMID:27052531

The atypical excretion profile of meldonium: Comparison of urinary detection windows after single- and multiple-dose application in healthy volunteers.

PubMed

Görgens, Christian; Guddat, Sven; Bosse, Christina; Geyer, Hans; Pop, Valentin; Schänzer, Wilhelm; Thevis, Mario

2017-05-10

Following a one-year monitoring program providing unequivocal analytical evidence for a high prevalence in international elite sports, meldonium has been included in the World Anti-Doping Agency's (WADA) list of prohibited substances that came into effect on 1 January 2016. Despite of the polar and hydrophilic nature of the molecule, an unusual long detection window was observed in pilot elimination studies. Consequently, in the present study, urinary excretion profiles after single-dose (5 volunteers, 1×500mg) and multiple-dose oral application (5 volunteers; 2×500mg/day for 6days) were determined in order to facilitate the result management concerning meldonium findings in doping controls. Particularly the option to differentiate between recent use and tapering concentrations was studied. Urinary meldonium concentrations were determined using an analytical approach based on hydrophilic interaction liquid chromatography and high resolution tandem mass spectrometry. The study corroborates the hypothesis of a non-linear, dose-depended and biphasic excretion profile after oral application of meldonium and demonstrates that urinary detection windows are of considerable extent with up to 65 and 117days (concentrations>LOQ of 10ng/mL) following single- and multiple-dose applications, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploratory urinary metabolomics of type 1 leprosy reactions.

PubMed

Mayboroda, Oleg A; van Hooij, Anouk; Derks, Rico; van den Eeden, Susan J F; Dijkman, Karin; Khadge, Saraswoti; Thapa, Pratibha; Kunwar, Chhatra B; Hagge, Deanna A; Geluk, Annemieke

2016-04-01

Leprosy is an infectious disease caused by Mycobacterium leprae that affects the skin and nerves. Although curable with multidrug therapy, leprosy is complicated by acute inflammatory episodes called reactions, which are the major causes of irreversible neuropathy in leprosy that occur before, during, and even after treatment. Early diagnosis and prompt treatment of reactions reduces the risk of permanent disability. This exploratory study investigated whether urinary metabolic profiles could be identified that correlate with early signs of reversal reactions (RR). A prospective cohort of leprosy patients with and without reactions and endemic controls was recruited in Nepal. Urine-derived metabolic profiles were measured longitudinally. Thus, a conventional area of biomarker identification for leprosy was extended to non-invasive urine testing. It was found that the urinary metabolome could be used to discriminate endemic controls from untreated patients with mycobacterial disease. Moreover, metabolic signatures in the urine of patients developing RR were clearly different before RR onset compared to those at RR diagnosis. This study indicates that urinary metabolic profiles are promising host biomarkers for the detection of intra-individual changes during acute inflammation in leprosy and could contribute to early treatment and prevention of tissue damage. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prenatal arsenic exposure and the epigenome: altered microRNAs associated with innate and adaptive immune signaling in newborn cord blood.

PubMed

Rager, Julia E; Bailey, Kathryn A; Smeester, Lisa; Miller, Sloane K; Parker, Joel S; Laine, Jessica E; Drobná, Zuzana; Currier, Jenna; Douillet, Christelle; Olshan, Andrew F; Rubio-Andrade, Marisela; Stýblo, Miroslav; García-Vargas, Gonzalo; Fry, Rebecca C

2014-04-01

The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. Copyright © 2013 Wiley Periodicals, Inc.

Cytokines profile and its correlation with endothelial damage and oxidative stress in patients with type 1 diabetes mellitus and nephropathy.

PubMed

Pestana, Rodrigo M C; Domingueti, Caroline P; Duarte, Rita C F; Fóscolo, Rodrigo B; Reis, Janice S; Rodrigues, Ana Maria S; Martins, Laís B; Sousa, Lirlândia P; Lage, Daniela P; Ferreira, Cláudia N; Ferreira, Adaliene V M; Fernandes, Ana P; Gomes, Karina B

2016-08-01

The aim of the present study was to investigate the association between the presence of albuminuria and cytokines profile with biomarkers of endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 63 DM1 patients with normoalbuminuria (<30 mg of albumin/g of creatinine) and 62 DM1 patients with micro- and macroalbuminuria (≥30 mg of albumin/g of creatinine). Plasma and urinary cytokines (TNF-α, IL-6 and IL-10) and thrombomodulin levels were determined by ELISA. Oxidative status was evaluated using the TBARS and MTT assays. Diabetic patients were characterized by elevated levels of urinary cytokines TNF-α, IL-6 and IL-10. Those with macroalbuminuria presented significantly higher TNF-α and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-α were positively correlated with plasma levels of cystatin C, creatinine, urea and albuminuria, while they were negatively correlated with estimated glomerular filtration rate. Urinary IL-10 levels proved positive correlation with fasting glucose, HbA1c, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Only urinary TNF-α levels were associated with the presence and severity of macroalbuminuria, after logistic regression analysis. This finding suggests that measurement of urinary TNF-α level may be helpful to evaluate progression to nephropathy in DM1 patients.

A study to investigate the chemical stability of gallium phosphate oxide/gallium arsenide phosphide

NASA Technical Reports Server (NTRS)

Kuhlman, G. J.

1979-01-01

The elemental composition with depth into the oxide films was examined using secondary ion mass spectrometry. Results indicate that the layers are arsenic-deficient through the bulk of the oxide and arsenic-rich near both the oxide surface and the oxide-semiconductor interface region. Phosphorus is incorporated into the oxide in an approximately uniform manner. The MIS capacitor structures exhibited deep-depletion characteristics and hysteresis indicative of electron trapping at the oxide-semiconductor interface. Post-oxidation annealing of the films in argon or nitrogen generally results in slightly increased dielectric leakage currents and decreased C-V hysteresis effects, and is associated with arsenic loss at the oxide surface. The results of bias-temperature stress experiments indicate that the major instability effects are due to changes in the electron trapping behavior. No changes were observed in the elemental profiles following electrical stressing, indicating that the grown films are chemically stable under device operating conditions.

Expression profiling of Crambe abyssinica under arsenate stress identifies genes and gene networks involved in arsenic metabolism and detoxification

PubMed Central

2010-01-01

Background Arsenic contamination is widespread throughout the world and this toxic metalloid is known to cause cancers of organs such as liver, kidney, skin, and lung in human. In spite of a recent surge in arsenic related studies, we are still far from a comprehensive understanding of arsenic uptake, detoxification, and sequestration in plants. Crambe abyssinica, commonly known as 'abyssinian mustard', is a non-food, high biomass oil seed crop that is naturally tolerant to heavy metals. Moreover, it accumulates significantly higher levels of arsenic as compared to other species of the Brassicaceae family. Thus, C. abyssinica has great potential to be utilized as an ideal inedible crop for phytoremediation of heavy metals and metalloids. However, the mechanism of arsenic metabolism in higher plants, including C. abyssinica, remains elusive. Results To identify the differentially expressed transcripts and the pathways involved in arsenic metabolism and detoxification, C. abyssinica plants were subjected to arsenate stress and a PCR-Select Suppression Subtraction Hybridization (SSH) approach was employed. A total of 105 differentially expressed subtracted cDNAs were sequenced which were found to represent 38 genes. Those genes encode proteins functioning as antioxidants, metal transporters, reductases, enzymes involved in the protein degradation pathway, and several novel uncharacterized proteins. The transcripts corresponding to the subtracted cDNAs showed strong upregulation by arsenate stress as confirmed by the semi-quantitative RT-PCR. Conclusions Our study revealed novel insights into the plant defense mechanisms and the regulation of genes and gene networks in response to arsenate toxicity. The differential expression of transcripts encoding glutathione-S-transferases, antioxidants, sulfur metabolism, heat-shock proteins, metal transporters, and enzymes in the ubiquitination pathway of protein degradation as well as several unknown novel proteins serve as molecular evidence for the physiological responses to arsenate stress in plants. Additionally, many of these cDNA clones showing strong upregulation due to arsenate stress could be used as valuable markers. Further characterization of these differentially expressed genes would be useful to develop novel strategies for efficient phytoremediation as well as for engineering arsenic tolerant crops with reduced arsenic translocation to the edible parts of plants. PMID:20546591

Arsenic-related water quality with depth and water quality of well-head samples from production wells, Oklahoma, 2008

USGS Publications Warehouse

Becker, Carol J.; Smith, S. Jerrod; Greer, James R.; Smith, Kevin A.

2010-01-01

The U.S. Geological Survey well profiler was used to describe arsenic-related water quality with well depth and identify zones yielding water with high arsenic concentrations in two production wells in central and western Oklahoma that yield water from the Permian-aged Garber-Wellington and Rush Springs aquifers, respectively. In addition, well-head samples were collected from 12 production wells yielding water with historically large concentrations of arsenic (greater than 10 micrograms per liter) from the Garber-Wellington aquifer, Rush Springs aquifer, and two minor aquifers: the Arbuckle-Timbered Hills aquifer in southern Oklahoma and a Permian-aged undefined aquifer in north-central Oklahoma. Three depth-dependent samples from a production well in the Rush Springs aquifer had similar water-quality characteristics to the well-head sample and did not show any substantial changes with depth. However, slightly larger arsenic concentrations in the two deepest depth-dependent samples indicate the zones yielding noncompliant arsenic concentrations are below the shallowest sampled depth. Five depth-dependent samples from a production well in the Garber-Wellington aquifer showed increases in arsenic concentrations with depth. Well-bore travel-time information and water-quality data from depth-dependent and well-head samples showed that most arsenic contaminated water (about 63 percent) was entering the borehole from perforations adjacent to or below the shroud that overlaid the pump. Arsenic concentrations ranged from 10.4 to 124 micrograms per liter in 11 of the 12 production wells sampled at the well head, exceeding the maximum contaminant level of 10 micrograms per liter for drinking water. pH values of the 12 well-head samples ranged from 6.9 to 9. Seven production wells in the Garber-Wellington aquifer had the largest arsenic concentrations ranging from 18.5 to 124 micrograms per liter. Large arsenic concentrations (10.4-18.5) and near neutral to slightly alkaline pH values (6.9-7.4) were detected in samples from one well in the Garber-Wellington aquifer, three production wells in the Rush Springs aquifer, and one well in an undefined Permian-aged aquifer. All well-head samples were oxic and arsenate was the only species of arsenic in water from 10 of the 12 production wells sampled. Arsenite was measured above the laboratory reporting level in water from a production well in the Garber-Wellington aquifer and was the only arsenic species measured in water from the Arbuckle-Timbered Hills aquifer. Fluoride and uranium were the only trace elements, other than arsenic, that exceeded the maximum contaminant level for drinking water in well-head samples collected for the study. Uranium concentrations in four production wells in the Garber-Wellington aquifer ranged from 30.2 to 99 micrograms per liter exceeding the maximum contaminant level of 30 micrograms per liter for drinking water. Water from these four wells also had the largest arsenic concentrations measured in the study ranging from 30 to 124 micrograms

Multiple metal exposures and their correlation with monoamine neurotransmitter metabolism in Chinese electroplating workers.

PubMed

Wu, Lin-Lin; Gong, Wei; Shen, Si-Peng; Wang, Zhong-He; Yao, Jia-Xi; Wang, Jun; Yu, Jing; Gao, Rong; Wu, Gang

2017-09-01

Excessive metal exposure has been recognized as one of the detrimental factors for brain damage. However, the potential adverse effects induced by heavy metals on monoamine neurotransmitter pathways remains poorly understood. Our study aimed to investigate the possible association between metal exposure and neurotransmitter metabolism. By a cross-sectional investigation, 224 electroplating workers and 213 non-electroplating exposure workers were recruited in the exposure and control groups. Metal exposure levels were analyzed using inductively-coupled plasma mass spectrometry and monoamine neurotransmitter pathway metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in human urine samples. Multivariate linear regression model was used to assess the dose-response relationships of urinary metals and neurotransmitter pathway metabolites. Significant dose-dependent trends of urinary vanadium quartiles with all metabolites were observed, and the trends demonstrated significance after multiple testing correction. It also showed that urinary chromium levels were significantly associated with decreased serotonin level and cadmium was positively associated with norepinephrine and epinephrine. In addition, arsenic was positively associated with tryptophan, serotonin, dopamine and norepinephrine. Iron was positively associated with increased homovanillic acid (HVA) and epinephrine while nickel was negatively associated with increased epinephrine levels. Zinc was positively related to tryptophan, kynurenin (KYN), 5-hydroxyindole acetic acid (5-HIAA), dopamine, HVA and norepinephrine. There was no significant association between urinary copper with any other metabolites after adjusting of multiple metal models. Metal exposure may be associated with neurotransmitter metabolism disturbances. The present work is expected to provide some support in the prevention and management of metal-associated neurological diseases. Copyright © 2017. Published by Elsevier Ltd.

Arsenic-based Life: An active learning assignment for teaching scientific discourse.

PubMed

Jeremy Johnson, R

2017-01-02

Among recent high profile scientific debates was the proposal that life could exist with arsenic in place of phosphorous in its nucleic acids and other biomolecules. Soon after its initial publication, scientists across diverse disciplines began to question this extraordinary claim. Using the original article, its claims, its scientific support, and the ensuing counterarguments, a two-day, active learning classroom exercise was developed focusing on the presentation, evaluation, and discussion of scientific argumentation and discourse. In this culminating assignment of a first semester biochemistry course, undergraduate students analyze the scientific support from the original research articles and then present and discuss multiple scientific rebuttals in a lively, civil classroom debate. Through this assignment, students develop a sense of skepticism, especially for the original arsenic-based life claims, and learn to clearly articulate their counterarguments with scientific support and critical reasoning. With its direct integration into first-semester biochemistry curriculum and the excitement surrounding arsenic based life, this assignment provides a robust, simple, and stimulating framework for introducing scientific discourse and active learning into the undergraduate molecular science curriculum. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):40-45, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

Transcriptional profile of diurnon-induces toxicity on the urinary bladder of male wistar rats to inform mode of action

EPA Science Inventory

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that induces rat urinary bladder urothelial tumors at high dietary levels (2500 ppm). The specific mode of action and molecular alterations triggered by diuron, however, have not been clarified. Th...

Mitochondria are the main target organelle for trivalent monomethylarsonous acid (MMA(III))-induced cytotoxicity.

PubMed

Naranmandura, Hua; Xu, Shi; Sawata, Takashi; Hao, Wen Hui; Liu, Huan; Bu, Na; Ogra, Yasumitsu; Lou, Yi Jia; Suzuki, Noriyuki

2011-07-18

Excessive generation of reactive oxygen species (ROS) is considered to play an important role in arsenic-induced carcinogenicity in the liver, lungs, and urinary bladder. However, little is known about the mechanism of ROS-based carcinogenicity, including where the ROS are generated, and which arsenic species are the most effective ROS inducers. In order to better understand the mechanism of arsenic toxicity, rat liver RLC-16 cells were exposed to arsenite (iAs(III)) and its intermediate metabolites [i.e., monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III))]. MMA(III) (IC(50) = 1 μM) was found to be the most toxic form, followed by DMA(III) (IC(50) = 2 μM) and iAs(III) (IC(50) = 18 μM). Following exposure to MMA(III), ROS were found to be generated primarily in the mitochondria. DMA(III) exposure resulted in ROS generation in other organelles, while no ROS generation was seen following exposures to low levels of iAs(III). This suggests the mechanisms of induction of ROS are different among the three arsenicals. The effects of iAs(III), MMA(III), and DMA(III) on activities of complexes I-IV in the electron transport chain (ETC) of rat liver submitochondrial particles and on the stimulation of ROS production in intact mitochondria were also studied. Activities of complexes II and IV were significantly inhibited by MMA(III), but only the activity of complexes II was inhibited by DMA(III). Incubation with iAs(III) had no inhibitory effects on any of the four complexes. Generation of ROS in intact mitochondria was significantly increased following incubation with MMA(III), while low levels of ROS generation were observed following incubation with DMA(III). ROS was not produced in mitochondria following exposure to iAs(III). The mechanism underlying cell death is different among As(III), MMA(III), and DMA(III), with mitochondria being one of the primary target organelles for MMA(III)-induced cytotoxicity. © 2011 American Chemical Society

[Etiology and antimicrobial resistance profile of urinary tract infection in children, Valdivia 2012].

PubMed

Herrera, Carolina; Navarro, Diego; Täger, Marlis

2014-12-01

Since initial antibiotic treatment in patients with urinary tract infection (UTI) is empiric, is very important to know the local epidemiology to make the correct therapeutical decisions. Determinate local features of antimicrobial resistance in pediatric patients with UTI. Retrospective review of urine culture tests of children under 15 years old, obtained in a pediatric emergency department in Valdivia, between february and december 2012. Escherichia coli showed high percentage of resistance to ampicillin (44,8%) and first generation cephalosporin (36%). A well understanding of local antimicrobial resistance profile is useful to a correct empiric treatment.

Urinary and Rectal Toxicity Profiles After Permanent Iodine-125 Implant Brachytherapy in Japanese Men: Nationwide J-POPS Multi-institutional Prospective Cohort Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohashi, Toshio, E-mail: ohashi@rad.med.keio.ac.jp; Yorozu, Atsunori; Saito, Shiro

Purpose: To assess, in a nationwide multi-institutional cohort study begun in 2005 and in which 6927 subjects were enrolled by 2010, the urinary and rectal toxicity profiles of subjects who enrolled during the first 2 years, and evaluate the toxicity profiles for permanent seed implantation (PI) and a combination therapy with PI and external beam radiation therapy (EBRT). Methods and Materials: Baseline data for 2339 subjects out of 2354 patients were available for the analyses. Toxicities were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, and the International Prostate Symptom Scores were recorded prospectively until 36 months after radiationmore » therapy. Results: Grade 2+ acute urinary toxicities developed in 7.36% (172 of 2337) and grade 2+ acute rectal toxicities developed in 1.03% (24 of 2336) of the patients. Grade 2+ late urinary and rectal toxicities developed in 5.75% (133 of 2312) and 1.86% (43 of 2312) of the patients, respectively. A higher incidence of grade 2+ acute urinary toxicity occurred in the PI group than in the EBRT group (8.49% vs 3.66%; P<.01). Acute rectal toxicity outcomes were similar between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late urinary toxicities were 6.04% versus 4.82% for the PI and the EBRT groups, respectively, with no significant differences between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late rectal toxicities were 0.90% versus 5.01% (P<.01) for the PI and the EBRT groups, respectively. The mean of the postimplant International Prostate Symptom Score peaked at 3 months, but it decreased to a range that was within 2 points of the baseline score, which was observed in 1625 subjects (69.47%) at the 1-year follow-up assessment. Conclusions: The acute urinary toxicities observed were acceptable given the frequency and retention, and the late rectal toxicities were more favorable than those of other studies.« less

Distribution of elements in individual blood cells in metabolic disorders at the cellular level

NASA Astrophysics Data System (ADS)

Johansson, Erland; Lindh, Ulf

1985-08-01

In comparison with controls neutrophil granulocytes from Rheumatoid arthritis (RA), Infantile Neuronal Ceroid Lipofuscinosis (INCL), Chronic Lymphatic Leukemia (L) and Aplastic Anemia (AA) displayed significant alterations in essential and non-essential elements which might be interpreted as fingerprints of these deseases. The neutrophils from RA patients displayed alterations in the concentrations of iron, calcium, strontium, manganese, zinc and copper. INCL displayed alterations in the concentrations of iron and copper but in the INCL disease the iron concentration was about 2 times higher than in RA. In leukemia, aluminium was observed but not in the controls (< 0.5 μg/ g). The zinc concentration was lowered in leukemia. Aplastic anemia displayed alterations in zirconium, arsenic, molybdenum, iron and zinc. The platelets from RA, INCL, L and AA patients also displayed alterations in the elemental profiles. The platelets from AA patients displayed a unique elemental distribution of arsenic, zirconium and molybdenum. The elemental profiles of the thrombocytes and neutrophils might be used as a complement in the diagnosis of the examined diseases and in therapy the elemental profile might be used to monitor drugs at the cellular level.

Rare emergence of symptoms during long-term asymptomatic Escherichia coli 83972 carriage without an altered virulence factor repertoire.

PubMed

Köves, Béla; Salvador, Ellaine; Grönberg-Hernández, Jenny; Zdziarski, Jaroslaw; Wullt, Björn; Svanborg, Catharina; Dobrindt, Ulrich

2014-02-01

Asymptomatic bacteriuria established by intravesical inoculation of Escherichia coli 83972 is protective in patients with recurrent urinary tract infections. In this randomized, controlled crossover study a total of 3 symptomatic urinary tract infection episodes developed in 2 patients while they carried E. coli 83972. We examined whether virulence reacquisition by symptom isolates may account for the switch from asymptomatic bacteriuria to symptomatic urinary tract infection. We used E. coli 83972 re-isolates from 2 patients in a prospective study and from another 2 in whom symptoms developed after study completion. We phylogenetically classified the re-isolates, and identified the genomic restriction patterns and gene expression profiles as well as virulence gene structure and phenotypes. In vivo virulence was examined in the murine urinary tract infection model. The fim, pap, foc, hlyA, fyuA, iuc, iroN, kpsMT K5 and malX genotypes of the symptomatic re-isolates remained unchanged. Bacterial gene expression profiles of flagellated symptomatic re-isolates were unique to each host, providing no evidence of common deregulation. Symptomatic isolates did not differ in virulence from the wild-type strain, as defined in the murine urinary tract infection model by persistence, symptoms or innate immune activation. The switch from asymptomatic E. coli 83972 carriage to symptomatic urinary tract infection was not explained by reversion to a functional virulence gene repertoire. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Selected markers of cardiovascular disease in a population exposed to arsenic from drinking water.

PubMed

Bošnjak, Zinka; Cavar, Suzana; Klapec, Tomislav; Milić, Marija; Klapec-Basar, Mirta; Toman, Miroslav

2008-09-01

This study examined prevalence and serum levels of selected markers of cardiovascular disease in 34 subjects from a Croatian rural population exposed to high levels of arsenic (As) from drinking water (611.89±10.06μg/l). The prevalences of overweight and obese subjects in the population were 32% and 35%. Half the subjects had hypertension, 29% had increased fasting serum glucose level and two were diabetic. Median total cholesterol (5.82mmol/l) and triglycerides (2.15mmol/l) were above the desirable margins. The median C-reactive protein level (1.20mg/l) was slightly higher than previously reported for healthy subjects. Serum Hsp70 level was significantly higher in nonsmokers. Total urinary As levels were positively correlated with age-adjusted serum levels of cobalamin. Near significance were also serum total bilirubin, antibodies to Hsp60 and folate. Tentative investigation of risk factors among subjects classified by tumor necrosis factor-α -308G/A and interleukin-6-174G/C gene polymorphisms was also performed. Collectively, the results are in agreement with the hypothesis of As-induced and/or compounded cardiovascular disease. Copyright © 2008 Elsevier B.V. All rights reserved.

Arsenic exposures alter clinical indicators of anemia in a male population of smokers and non-smokers in Bangladesh.

PubMed

Parvez, Faruque; Medina, Sebastian; Santella, Regina M; Islam, Tariqul; Lauer, Fredine T; Alam, Nur; Eunus, Mahbubul; Rahman, Mizanour; Factor-Litvak, Pam; Ahsan, Habib; Graziano, Joseph H; Liu, Ke Jian; Burchiel, Scott W

2017-09-15

Drinking water arsenic (WAs) exposure has been linked to a number of detrimental health outcomes including anemia, primarily among pregnant women. Little is known about the effects of arsenic (As) on hematological disorders among men. We have examined the role of As exposure on hematological indicators of anemia in a group of men exposed to a wide range of As in their drinking water. We conducted a cross-sectional investigation among 119 healthy men in the Health Effects of As Longitudinal Study (HEALS) cohort, in rural Bangladesh. The participants are part of an ongoing study focused on evaluating the influence of As and smoking on immune function. Samples were collected at recruitment and analyzed for water As, urinary As (UAs) and UAs metabolites to assess As exposure. Blood samples were also collected at recruitment and assayed immediately for hematological parameters. We found that increased WAs levels were associated with decreased red blood cell counts [β=-0.13, p<0.0001] as well as hematocrit packed cell volumes [β=-0.68, p=0.008] following adjustment for age, smoking, body mass index and polycyclic aromatic hydrocarbon-DNA adducts. Other measures of As exposure (UAs and its metabolites) demonstrated similar associations. Slightly stronger effects were observed among smokers. We also observed an effect of As on hemoglobin among smokers in relation to UAs [β=-0.54, p<0.05]. Our analysis revealed effects of As exposure on hematological indicators of anemia in a group of healthy male smokers and non-smokers. Copyright © 2017 Elsevier Inc. All rights reserved.

Exploring the in vitro formation of trimethylarsine sulfide from dimethylthioarsinic acid in anaerobic microflora of mouse cecum using HPLC-ICP-MS and HPLC-ESI-MS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubachka, Kevin M.; Kohan, Michael C.; Herbin-Davis, Karen

Although metabolism of arsenicals to form methylated oxoarsenical species has been extensively studied, less is known about the formation of thiolated arsenical species that have recently been detected as urinary metabolites. Indeed, their presence suggests that the metabolism of ingested arsenic is more complex than previously thought. Recent reports have shown that thiolated arsenicals can be produced by the anaerobic microflora of the mouse cecum, suggesting that metabolism prior to systemic absorption may be a significant determinant of the pattern and extent of exposure to various arsenic-containing species. Here, we examined the metabolism of {sup 34}S labeled dimethylthioarsinic acid ({supmore » 34}S-DMTA{sup V}) by the anaerobic microflora of the mouse cecum using HPLC-ICP-MS and HPLC-ESI-MS/MS to monitor for the presence of various oxo- and thioarsenicals. The use of isotopically enriched {sup 34}S-DMTA{sup V} made it possible to differentiate among potential metabolic pathways for production of the trimethylarsine sulfide (TMAS{sup V}). Upon in vitro incubation in an assay containing anaerobic microflora of mouse cecum, {sup 34}S-DMTA{sup V} underwent several transformations. Labile {sup 34}S was exchanged with more abundant {sup 32}S to produce {sup 32}S-DMTA{sup V}, a thiol group was added to yield DMDTA{sup V}, and a methyl group was added to yield {sup 34}S-TMAS{sup V}. Because incubation of {sup 34}S-DMTA{sup V} resulted in the formation of {sup 34}S-TMAS{sup V}, the pathway for its formation must preserve the arsenic-sulfur bond. The alternative metabolic pathway postulated for formation of TMAS{sup V} from dimethylarsinic acid (DMA{sup V}) would proceed via a dimethylarsinous acid (DMA{sup III}) intermediate and would necessitate the loss of {sup 34}S label. Structural confirmation of the metabolic product was achieved using HPLC-ESI-MS/MS. The data presented support the direct methylation of DMTA{sup V} to TMAS{sup V}. Additionally, the detection of isotopically pure {sup 34}S-TMAS{sup V} raises questions about the sulfur exchange properties of TMAS{sup V} in the cecum material. Therefore, {sup 34}S-TMAS{sup V} was incubated and the exchange was monitored with respect to time. The data suggest that the As-S bond associated with TMAS{sup V} is less labile than the As-S bond associated with DMTA{sup V}.« less

NMR-based urinary profiling of lactulose/mannitol ratio used to assess the altered intestinal permeability in acute on chronic liver failure (ACLF) patients.

PubMed

Kumar, Dinesh; Pandey, Gaurav; Bansal, Deepak; Rawat, Atul; Kumar, Umesh; Dubey, Durgesh; Guleria, Anupam; Saraswat, Vivek Anand

2017-04-01

The article presents a simplified NMR-based protocol for urinary profiling of lactulose/mannitol ratio (LMR) and demonstrates here its utility to assess increased intestinal permeability (IP) in patients with acute on chronic liver failure (ACLF). ACLF is a serious clinical complication associated with chronic liver disease (cirrhosis). The major risk factor in its development is increased IP ('leaky gut'), which has been linked to disease progression and to infectious complications. However, IP has seldom been investigated in patients with ACLF, even though patients frequently report gastrointestinal disorders and associated complications. To this end, we first optimized the NMR-based targeted profiling of urinary metabolites (i.e. actulose, mannitol, and creatinine) and subsequently used this resulted protocol (a) first to evaluate the altered IP in ACLF patients and then (b) to explore its utility for monitoring the treatment response in these patients. The normal profiles were obtained for 7 age and sex matched healthy volunteers. The results revealed that the urinary LMR excretion was significantly higher in ACLF patients compared to normal controls (median ~0.7, range (0.12-2.84), vs median ~0.11, range (0.02-0.28), p < 0.001) suggesting that the ACLF patients' exhibit altered IP. However, the LMR excretion in six clinically improved follow-up ACLF patients was comparable to normal controls indicating restored IP after the treatment. The protocol-as demonstrated here with ACLF-is equally applicable for evaluating IP or mucosal barrier function in other intestinal disorders with reasonable sensitivity and specificity, highlighting its general utility. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Metabolism and toxicity of arsenicals in mammals.

PubMed

Sattar, Adeel; Xie, Shuyu; Hafeez, Mian Abdul; Wang, Xu; Hussain, Hafiz Iftikhar; Iqbal, Zahid; Pan, Yuanhu; Iqbal, Mujahid; Shabbir, Muhammad Abubakr; Yuan, Zonghui

2016-12-01

Arsenic (As) is a metalloid usually found in organic and inorganic forms with different oxidation states, while inorganic form (arsenite As-III and arsenate As-v) is considered to be more hazardous as compared to organic form (methylarsonate and dimethylarsinate), with mild or no toxicity in mammals. Due to an increasing trend to using arsenicals as growth promoters or for treatment purposes, the understanding of metabolism and toxicity of As gets vital importance. Its toxicity is mainly depends on oxi-reduction states (As-III or As-v) and the level of methylation during the metabolism process. Currently, the exact metabolic pathways of As have yet to be confirmed in humans and food producing animals. Oxidative methylation and glutathione conjugation is believed to be major pathways of As metabolism. Oxidative methylation is based on conversion of Arsenite in to mono-methylarsonic acid and di-methylarsenic acid in mammals. It has been confirmed that As is only methylated in the presence of glutathione or thiol compounds, suggesting that As is being methylated in trivalent states. Subsequently, non-conjugated trivalent arsenicals are highly reactive with thiol which converts the trivalent arsenicals in to less toxic pentavalent forms. The glutathione conjugate stability of As is the most important factor for determining the toxicity. It can lead to DNA damage by alerting enzyme profile and production of reactive oxygen and nitrogen species which causes the oxidative stress. Moreover, As causes immune-dysfunction by hindering cellular and humeral immune response. The present review discussed different metabolic pathways and toxic outcomes of arsenicals in mammals which will be helpful in health risk assessment and its impact on biological world. Copyright © 2016. Published by Elsevier B.V.

Arsenic associations in sediments from shallow aquifers of northwestern Hetao Basin, Inner Mongolia

USGS Publications Warehouse

Deng, Y.; Wang, Y.; Ma, T.; Yang, H.; He, J.

2011-01-01

Understanding the mechanism of arsenic mobilization from sediments to groundwater is important for water quality management in areas of endemic arsenic poisoning, such as the Hetao Basin in Inner Mongolia, northern China. Aquifer geochemistry was characterized at three field sites (SH, HF, TYS) in Hangjinhouqi County of northwestern Hetao Basin. The results of bulk geochemistry analysis of sediment samples indicated that total As concentrations have a range of 6. 8-58. 5 mg/kg, with a median of 14. 4 mg/kg. The highest As concentrations were found at 15-25 m depth. In the meanwhile, the range of As concentration in the sediments from background borehole is 3-21. 8 mg/kg, with a median value of 9 mg/kg. The As sediments concentrations with depth from the SH borehole were correlated with the contents of Fe, Sb, B, V, total C and total S. Generally, the abundance of elements varied with grain size, with higher concentrations in finer fractions of the sediments. Distinct lithology profile and different geochemical characteristics of aquifer sediments indicate the sediments are associated with different sources and diverse sedimentary environments. Up to one third of arsenic in the sediments could be extracted by ammonium oxalate, suggesting that Fe oxyhydroxides may be the major sink of As in the aquifer. Sequential extraction results indicate that arsenic occurs as strongly adsorbed on and/or co-precipitated with amorphous Fe oxyhydroxides in sediments accounting for 35 and 20%, respectively, of the total contents of arsenic. The release of As into groundwater may occur by desorption from the mineral surface driven by reductive dissolution of the Fe oxide minerals. Furthermore, small proportions of As associated with iron sulfides occur in the reductive sediments. ?? 2011 Springer-Verlag.

Evaluation of biochemical changes in chronic arsenic poisoning among Bangladeshi patients.

PubMed

Nabi, A H M Nurun; Rahman, M Mahfuzur; Islam, Laila N

2005-12-01

An estimated 40 million people in Bangladesh have been suffering from arsenic toxicity-related diseases because of drinking water contamination with high levels of naturally occurring arsenic. To evaluate the biochemical changes in chronic arsenic exposure, a total of 115 exposed subjects diagnosed as arsenicosis patients were examined and interviewed, and 120 unexposed volunteers were enrolled in this study. Drinking water, urine and peripheral blood samples were collected from all participants and analyzed. The average levels of arsenic in the drinking water and spot urine samples of the arsenicosis patients were 218.1 microg/L and 234.6 microg/L, respectively, and duration of exposure was 7.6 +/- 5.2 yrs that ranged from 1-25 yrs. Prevalence of diabetes mellitus among chronic arsenic-exposed subjects was about 2.8 times higher than the unexposed subjects. The activities of alkaline phosphatase were significantly elevated in the patients, 197 U/L compared to 149 U/L in the controls, but alanine transaminase and aspartate transaminase were mostly normal. The patients had significantly lower levels of serum creatinine, 0.97 mg/dL compared to 1.15 mg/dL in the controls; but had significantly elevated levels of total protein, 84 g/L and 77 g/L respectively. The mean level of inorganic phosphate in the serum of arsenicosis patients was 6.4 mg/dL compared to 4.6 mg/dL in the unexposed subjects and the level was significantly higher, indicating substitution of the pentavalent arsenate for the phosphate ion causing underutilization of the latter. Evaluation of the lipid profiles showed while the levels of triacylglycerol were not much different, the patients had significantly lower levels of cholesterol, HDL-cholesterol and LDL-cholesterol compared to the unexposed subjects. These findings suggest significant changes in biochemical parameters in human arsenic toxicity.

[Ecology and fluoroquinolon resistance profiles in febrile urinary tract infections (FUTI) after prostate needle biopsy: A retrospective study in 466 biopsies].

PubMed

Duboureau, H; Achkar, K; Stephan, R; Schmit, J L; Saint, F

2017-05-01

The biopsies of prostate are the reference examination to assert the diagnosis of prostate cancer. Even if the urinary infectious complications are rare thanks to the systematic oral antibiotic prophylaxis, they may still be serious. The SPILF (Society of Infectious Pathology and French language) published in 2014, an important increase of the resistances in fluoroquinolones for Escherichia coli (3 to 25%), whereas this is the most bacterium frequently found in the urinary infections (70-80%). The objectives of this study were to estimate the indicence of the febrile urinary tract infections after prostate needle biopsy and to define the ecology and the profile of E. coli's resistance. A total of 466 transrectal ultrasound-guided needle prostate biopsy were included in the study from 2012 to 2015. All the patients were taken care according to the recommendations of the AFU (Ouzzane et al., 2011). We estimated, for all the inclusive patients, if they had presented a clinic sign of urinary infection like fever or burning which suggestive of an urinary infection, and having a urines and blood culture, in the next 30 days the realization of the medical exam. Among 466 realized biopsies, seven patients developed a febril urinary tract infection (1.5%) [prostatitis (n=6), orchitis (n=1)]. Five infections to E. coli were identified; two were resistant for fluoroquinolones (40%). No germ was able to be identified for two patients. The infectious complications post-biopsy of prostate are rare (1.5%). E. coli is the germ most frequently identified with 40% of resistance with fluoroquinolones. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Novel H6PDH mutations in two girls with premature adrenarche: 'apparent' and 'true' CRD can be differentiated by urinary steroid profiling.

PubMed

Lavery, G G; Idkowiak, J; Sherlock, M; Bujalska, I; Ride, J P; Saqib, K; Hartmann, M F; Hughes, B; Wudy, S A; De Schepper, J; Arlt, W; Krone, N; Shackleton, C H; Walker, E A; Stewart, P M

2013-02-01

Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase (H6PDH, encoded by H6PD) cause apparent cortisone reductase deficiency (ACRD). H6PDH generates cofactor NADPH for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by HSD11B1) oxo-reductase activity, converting cortisone to cortisol. Inactivating mutations in HSD11B1 cause true cortisone reductase deficiency (CRD). Both ACRD and CRD present with hypothalamic-pituitary-adrenal (HPA) axis activation and adrenal hyperandrogenism. To describe the clinical, biochemical and molecular characteristics of two additional female children with ACRD and to illustrate the diagnostic value of urinary steroid profiling in identifying and differentiating a total of six ACRD and four CRD cases. Clinical, biochemical and genetic assessment of two female patients presenting during childhood. In addition, results of urinary steroid profiling in a total of ten ACRD/CRD patients were compared to identify distinguishing characteristics. Case 1 was compound heterozygous for R109AfsX3 and a novel P146L missense mutation in H6PD. Case 2 was compound heterozygous for novel nonsense mutations Q325X and Y446X in H6PD. Mutant expression studies confirmed loss of H6PDH activity in both cases. Urinary steroid metabolite profiling by gas chromatography/mass spectrometry suggested ACRD in both cases. In addition, we were able to establish a steroid metabolite signature differentiating ACRD and CRD, providing a basis for genetic diagnosis and future individualised management. Steroid profile analysis of a 24-h urine collection provides a diagnostic method for discriminating between ACRD and CRD. This will provide a useful tool in stratifying unresolved adrenal hyperandrogenism in children with premature adrenarche and adult females with polycystic ovary syndrome (PCOS).

A Comparative Assessment of Arsenic Risks and the Nutritional Benefits of Fish Consumption in Kuwait: Arsenic Versus Omega 3-Fatty Acids.

PubMed

Husain, Adnan; Kannan, Kurunthachalam; Chan, Hing Man; Laird, Brian; Al-Amiri, Hanan; Dashti, Basma; Sultan, Anwar; Al-Othman, Amani; Mandekar, Bedraya

2017-01-01

Inorganic and organic forms of arsenic (As), as well as omega-3 fatty acids were measured in 578 fish/seafood samples that belong to 15 species of commonly consumed seafood in Kuwait. Arsenic speciation data, with the toxicological profile of inorganic arsenic (iAs) and fish consumption rates were applied in a probabilistic risk assessment to estimate the risk from exposure to iAs. The nutritional benefits of omega-3-fatty acid levels in various species of fish were taken into consideration. Results showed that the mean daily intake of iAs through fish consumption among the Kuwaiti population was 0.058 µg/kg/day, and the 95th percentile was 0.15 µg/kg/day. Although the mean intake level did not exceed the incremental lifetime cancer risk (ILCR) at 1 × 10 -4 , the 95th percentile of iAs intake showed an ILCR of 2.7 × 10 -4 . Kuwaiti children (aged 6-12 years) were found to have a higher mean intake of iAs at 0.10 µg/kg/day with 68% of children in this category, exceeding the risk specific dose associated with an ILCR of 1 × 10 -4 . The fish species, hammor (grouper; Epinephelus coioides), is the top contributor to iAs intake, and tuna is the major source of omega 3-fatty acids for the Kuwaiti population.

Nitrate, arsenic and chloride pollution of drinking water in Northern Greece. Elaboration by applying GIS.

PubMed

Fytianos, Konstantinos; Christophoridis, Christophoros

2004-01-01

The general profile of the pollution of drinking water, originating from groundwater, by nitrates, chloride and arsenic, in the Prefecture of Thessaloniki, was studied in this project. Samples (tap water) were collected from 52 areas-villages of the Prefecture, during a period of 6 months. The analytical results were related to certain points on the map of the area, thus producing coloured representations of the Prefecture, according to the concentration of the corresponding pollutant. The statistical analysis of the data led to some conclusions concerning the causes of pollution and the relation of the concentrations to certain physico-chemical parameters. Nitrate concentration of samples collected from two specific regions were especially high, sometimes above the highest permitted level. A limited number of samples (13.5%) contained arsenic concentrations above the imminent EC drinking water limit (10 ppb). The majority of the tap water samples, collected from areas along the seashore contained increased concentrations of chloride ions, which is a clear indication of seawater intrusion into the related aquifers.

Lifetime risk of urothelial carcinoma and lung cancer in the arseniasis-endemic area of Northeastern Taiwan

NASA Astrophysics Data System (ADS)

Yang, Tse-Yen; Hsu, Ling-I.; Chen, Hui-Chi; Chiou, Hung-Yi; Hsueh, Yu-Mei; Wu, Meei-Maan; Chen, Chi-Ling; Wang, Yuan-Hung; Liao, Ya-Tang; Chen, Chien-Jen

2013-11-01

Arsenic in drinking water has been shown to increase the risk of urothelial carcinoma and lung cancer. However, the lifetime risk of developing urothelial carcinoma and lung cancer caused by exposure to arsenic in drinking water has not been reported. This study aimed to assess the lifetime risk of urothelial carcinoma and lung cancer caused by arsenic exposure from drinking water and cigarette smoking habit for residents living in the arseniasis-endemic area in Northeastern Taiwan. We recruited 8086 residents in 1991-1994 and monitored them for their newly developed types of cancers, identified by computerized linkage with the national cancer registry profile. There were 37 newly diagnosed urothelial carcinoma cases and 223 new lung cancer cases during the follow-up period (until 2007). The lifetime (35-85 years old) cumulative risk of developing urothelial carcinoma from an arsenic concentration in the drinking water of <10, 10-99, and 100+ μg/L was 0.29%, 1.07% and 3.43%, respectively. The corresponding probabilities were 7.42%, 8.99% and 17.09% for the lifetime risk of developing lung cancer. Cigarette smoking was associated with an increased risk of urothelial carcinoma and lung cancer, showing the hazard ratio (95% confidence interval) of 2.48 (1.27-4.82) and 3.44 (2.00-5.90) after adjusting for the arsenic concentration in drinking water. After adjusting for cigarette smoking, the hazard ratio (95% confidence interval) of developing urothelial carcinoma caused by the arsenic concentration in drinking water of <10, 10-99 and 100+ μg/L was 1.0 (the reference group), 2.18 (0.59-8.01), and 8.71 (2.49-30.48), respectively. The corresponding figures were 1.0 (the reference group), 1.14 (0.80-1.61), 1.84 (1.28-2.65) for lung cancer. Synergistic effects on the development of urothelial carcinoma and lung cancer existed between the arsenic exposure level and cigarette smoking. It is suggested that people who have had a high exposure to arsenic in drinking water should stop smoking cigarettes to lower their lifetime risk of urothelial carcinoma and lung cancer.

Urinary heavy metals, phthalates, phenols, thiocyanate, parabens, pesticides, polyaromatic hydrocarbons but not arsenic or polyfluorinated compounds are associated with adult oral health: USA NHANES, 2011-2012.

PubMed

Shiue, Ivy

2015-10-01

Links between environmental chemicals and human health have emerged over the last few decades, but the effects on oral health have been less studied. Therefore, it was aimed to study the relationships of different sets of urinary chemical concentrations and adult oral health conditions in a national and population-based setting. Data was retrieved from the United States National Health and Nutrition Examination Surveys, 2011-2012 including demographics, self-reported oral health conditions and urinary environmental chemical concentrations (one third representative sample of the study population). Chi-square test, t test, and survey-weighted logistic and multi-nominal regression modeling were performed. Of 4566 American adults aged 30-80, 541 adults (11.9 %) reported poor teeth health while 1020 adults (22.4 %) reported fair teeth. Eight hundred fifty-five people (19.1 %) claimed to have gum disease, presented with higher levels of urinary cadmium, cobalt and polyaromatic hydrocarbons. Six hundred three adults (13.3 %) had bone loss around the mouth, presented with higher levels of cadmium, nitrate, thiocyanate, propyl paraben and polyaromatic hydrocarbons. Eight hundred forty-five adults (18.5 %) had tooth loose not due to injury, presented with higher level of cadmium, thiocyanate and polyaromatic hydrocarbons. Eight hundred forty-five adults (18.5 %) with higher levels of lead, uranium, polyaromatic hydrocarbons but lower level of triclosan noticed their teeth did not look right. Three hundred fifty-one adults (7.7 %) often had aching in the mouth and 650 (14.3 %) had it occasionally, presented with higher levels of phthalates, pesticides and polyaromatic hydrocarbons. Benzophenone-3 and triclosan elicited protective effects. Regulation of environmental chemicals in prevention of adult oral health might need to be considered in future health and environmental policies.

Multiple-metal exposure, diet, and oxidative stress in Uruguayan school children.

PubMed

Kordas, Katarzyna; Roy, Aditi; Vahter, Marie; Ravenscroft, Julia; Mañay, Nelly; Peregalli, Fabiana; Martínez, Gabriela; Queirolo, Elena I

2018-06-26

Oxidative stress (OS) is an important consequence of exposure to toxic metals but it is unclear to what extent low-level metal exposures contribute to OS in children. We examined the cross-sectional association between urinary concentrations of arsenic (As), cadmium (Cd), and lead (Pb) and urinary markers of OS: F 2 -8α isoprostane and 8-hydroxy-2-deoxy-guanosine (8-OHdG). We also tested effect modification by dietary intakes. Of the 211 children aged 6-8 years living in Montevideo who were eligible for the study because they had at least one OS marker measured via ELISA, 143 were included in a complete-case analysis. Urinary metals were measured with inductively coupled plasma mass spectrometry (ICP-MS: Pb, Cd) and high-performance liquid chromatography online with hydride generation ICP-MS (As-metabolites); concentrations were log 2 -transformed. All urinary markers were adjusted for specific gravity of urine. Two 24-h dietary recalls were conducted to estimate children's dietary intakes, including total fruit and vegetable consumption and vitamin C, zinc and fiber intake. Ordinary least square (OLS) and weighted quantile sum (WQS) regressions were used to estimate the association between metals and each OS marker as outcome. Metal exposure was generally low: median urinary As, Cd, Pb 9.6 μg/L, 0.06 μg/L and 1.9 μg/L, respectively. Median 8-isoprostane concentration was 1.1 and 8-OHdG 39.6 ng/mL. Log 2 -transformed urinary As concentrations were positively associated with 8-OHdG concentrations (10.90 [3.82, 17.97]) in covariate-adjusted OLS models which also took account of exposure to Cd and Pb. In WQS, a mixture index was also associated with higher 8-OHdG (8.71 [1.12, 16.3] for each 25% increase in index value), mostly driven by As exposure. There was little evidence of effect modification by dietary antioxidants. In sum, even at low-level, As exposure is associated with detectable oxidative damage to the DNA. Copyright © 2018 Elsevier Inc. All rights reserved.

Population structure and abundance of arsenite-oxidizing bacteria along an arsenic pollution gradient in waters of the upper isle River Basin, France.

PubMed

Quéméneur, Marianne; Cébron, Aurélie; Billard, Patrick; Battaglia-Brunet, Fabienne; Garrido, Francis; Leyval, Corinne; Joulian, Catherine

2010-07-01

Denaturing gradient gel electrophoresis (DGGE) and quantitative real-time PCR (qPCR) were successfully developed to monitor functional aoxB genes as markers of aerobic arsenite oxidizers. DGGE profiles showed a shift in the structure of the aoxB-carrying bacterial population, composed of members of the Alpha-, Beta- and Gammaproteobacteria, depending on arsenic (As) and E(h) levels in Upper Isle River Basin waters. The highest aoxB gene densities were found in the most As-polluted oxic surface waters but without any significant correlation with environmental factors. Arsenite oxidizers seem to play a key role in As mobility in As-impacted waters.

Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children

PubMed Central

Martin, Francois-Pierre; Su, Ming-Ming; Xie, Guo-Xiang; Guiraud, Seu Ping; Kussmann, Martin; Godin, Jean-Philippe; Jia, Wei; Nydegger, Andreas

2017-01-01

AIM To identify metabolic signatures in urine samples from healthy and inflammatory bowel disease (IBD) children. METHODS We applied liquid chromatography and gas chromatography coupled to targeted mass spectrometry (MS)-based metabolite profiling to identify and quantify bile acids and host-gut microbial metabolites in urine samples collected from 21 pediatric IBD patients monitored three times over one year (baseline, 6 and 12 mo), and 27 age- and gender-matched healthy children. RESULTS urinary metabolic profiles of IBD children differ significantly from healthy controls. Such metabolic differences encompass central energy metabolism, amino acids, bile acids and gut microbial metabolites. In particular, levels of pyroglutamic acid, glutamic acid, glycine and cysteine, were significantly higher in IBD children in the course of the study. This suggests that glutathione cannot be optimally synthesized and replenished. Whilst alterations of the enterohepatic circulation of bile acids in pediatric IBD patients is known, we show here that non-invasive urinary bile acid profiling can assess those altered hepatic and intestinal barrier dysfunctions. CONCLUSION The present study shows how non-invasive sampling of urine followed by targeted MS-based metabonomic analysis can elucidate and monitor the metabolic status of children with different GI health/disease status. PMID:28611517

Urinary volatile organic compounds as potential biomarkers for renal cell carcinoma

PubMed Central

WANG, DONGCHUN; WANG, CHANGSONG; PI, XIN; GUO, LEI; WANG, YUE; LI, MINGJUAN; FENG, YUE; LIN, ZIWEI; HOU, WEI; LI, ENYOU

2016-01-01

Currently, there is no adequate, sensitive, reproducible, specific and noninvasive biomarker that can reliably be used to detect renal cell carcinoma (RCC). Previous studies have elucidated the urinary non-volatile metabolic profile of RCC. However, whether urinary volatile organic compound (VOC) profiles are able to identify RCC remains to be elucidated. In the present study, urine was collected from 22 patients with RCC and 25 healthy subjects. Principal component analysis and orthogonal partial least square discriminant analysis were used to compare the data of patients and healthy subjects, and preoperative and postoperative patients undergoing radical nephrectomy. In total, 11 VOC biomarkers were elevated in the RCC patients compared to the healthy subjects, which were phenol; decanal; 1,6-dioxacyclododecane-7,12-dione; 1-bromo-1-(3-methyl-1-pentenylidene)-2,2,3,3-tetramethyl-cyclopropane; nonanal; 3-ethyl-3-methylheptane; isolongifolene-5-ol; 2,5-cyclohexadiene-1,4-dione, 2,6-bis(1,1-dimethylethyl); tetradecane; aniline; and 2,6,10,14-tetramethyl-pentadecane. Three biomarkers were decreased in RCC patients: styrene, 4-heptanone and dimethylsilanediol. In preoperative patients, 2-ethyl-1-hexanol and cyclohexanone were elevated, while 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne were decreased when compared to postoperative patients. Compared with the healthy subjects, RCC has a unique VOC profile, suggesting that VOC profiles may be a useful diagnostic assay for RCC. PMID:27347408

Use of urinary 13,14, dihydro-15-keto-prostaglandin F2α (PGFM) concentrations to diagnose pregnancy and predict parturition in the giant panda (Ailuropoda melanolecua).

PubMed

Roberts, Beth M; Brown, Janine L; Kersey, David C; Snyder, Rebecca J; Durrant, Barbara S; Kouba, Andrew J

2018-01-01

Pregnancy determination is difficult in the giant panda (Ailuropoda melanolecua), representing a challenge for ex situ conservation efforts. Research in other species experiencing pseudopregnancy indicates that urinary/fecal concentrations of 13,14, dihydro-15-keto-prostaglandin F2α (PGFM) can accurately determine pregnancy status. Our objective was to determine if urinary PGFM concentrations are associated with pregnancy status in the giant panda. Urinary PGFM concentrations were measured in female giant pandas (n = 4) throughout gestation (n = 6) and pseudopregnancy (n = 4) using a commercial enzyme immunoassay. Regardless of pregnancy status, PGFM excretion followed a predictable pattern: 1) baseline concentrations for 11-19 weeks following ovulation; 2) a modest, initial peak 14-36 days after the start of the secondary urinary progestagen rise; 3) a subsequent period of relatively low concentrations; and 4) a large, terminal peak at the end of the luteal phase. Pregnant profiles were distinguished by an earlier initial peak (P = 0.024), higher inter-peak concentrations (P < 0.001), and a larger terminal peak (P = 0.003) compared to pseudopregnancy profiles. Parturition occurred 23 to 25 days from the initial PGFM surge and within 24 hours of the start of the terminal increase. These pattern differences indicate that urinary PGFM monitoring can be used to predict pregnancy status and time parturition in the giant panda. Furthermore, this is the only species known to exhibit a significant PGFM increase during pseudopregnancy, suggesting a unique physiological mechanism for regulating the end of the luteal phase in the giant panda.

Dose response evaluation of gene expression profiles in the skin of K6/ODC mice exposed to sodium arsenite.

PubMed

Ahlborn, Gene J; Nelson, Gail M; Ward, William O; Knapp, Geremy; Allen, James W; Ouyang, Ming; Roop, Barbara C; Chen, Yan; O'Brien, Thomas; Kitchin, Kirk T; Delker, Don A

2008-03-15

Chronic drinking water exposure to inorganic arsenic and its metabolites increases tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, we characterized gene expression profiles from analysis of K6/ODC mice administered 0, 0.05, 0.25, 1.0 and 10 ppm sodium arsenite in their drinking water for 4 weeks. Following exposure, total RNA was isolated from mouse skin and processed to biotin-labeled cRNA for microarray analyses. Skin gene expression was analyzed with Affymetrix Mouse Genome 430A 2.0 GeneChips, and pathway analysis was conducted with DAVID (NIH), Ingenuity Systems and MetaCore's GeneGo. Differential expression of several key genes was verified through qPCR. Only the highest dose (10 ppm) resulted in significantly altered KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, including MAPK, regulation of actin cytoskeleton, Wnt, Jak-Stat, Tight junction, Toll-like, phosphatidylinositol and insulin signaling pathways. Approximately 20 genes exhibited a dose response, including several genes known to be associated with carcinogenesis or tumor progression including cyclin D1, CLIC4, Ephrin A1, STAT3 and DNA methyltransferase 3a. Although transcription changes in all identified genes have not previously been linked to arsenic carcinogenesis, their association with carcinogenesis in other systems suggests that these genes may play a role in the early stages of arsenic-induced skin carcinogenesis and can be considered potential biomarkers.

Exposure to polycyclic aromatic hydrocarbons, arsenic and environmental tobacco smoke, nutrient intake, and oxidative stress in Japanese preschool children.

PubMed

Mori, Takuya; Yoshinaga, Jun; Suzuki, Kei; Mizoi, Miho; Adachi, Shu-Ichi; Tao, Hiroaki; Nakazato, Tetsuya; Li, Yun-Shan; Kawai, Kazuaki; Kasai, Hiroshi

2011-07-01

The association between oxidative stress and exposure to environmental chemicals was assessed in a group of Japanese preschool children. The concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 1-hydroxypyrene (1-OHP), inorganic arsenic (iAs) and monomethylarsonic acid (MMA), and cotinine in spot urine samples, collected from 134 children (3-6 yrs) from a kindergarten in Kanagawa, Japan, were measured as biomarkers of oxidative stress or exposure to environmental chemicals. For 76 subjects of the 134, intakes of anti-oxidant nutrients (vitamins A, C, and E, manganese, copper, zinc and selenium (Se)) were estimated from a food consumption survey carried out 2-4 weeks after urine sampling and by urine analysis (Se). The median (min-max) creatinine-corrected concentrations of urinary biomarkers were 4.45 (1.98-12.3), 0.127 (0.04-2.41), 4.78 (1.18-12.7), and 0.62 (<0.6-19.0) μg/g cre for 8-OHdG, 1-OHP, iAs+MMA, and cotinine, respectively. Multiple regression analysis was carried out using 8-OHdG concentration as a dependent variable and urinary biomarkers of exposure and Se intake, intakes of vitamins and biological attributes of the subjects as independent variables. To explain 8-OHdG concentrations, intake of vitamin A and age were significant variables with negative coefficients, while 1-OHP concentration had a positive coefficient. These results indicated that oxidative stress of children is affected by chemical exposure at environmental levels, by nutrient intake and by physiological factors in a complex manner. On the other hand, unstable statistical results due to sub-grouping of subject, based on the availability of food consumption data, were found: the present results should further be validated by future studies with suitable research design. Copyright © 2011 Elsevier B.V. All rights reserved.

Quantitative Evaluation of Heavy Metals and Trace Elements in the Urinary Bladder: Comparison Between Cancerous, Adjacent Non-cancerous and Normal Cadaveric Tissue.

PubMed

Abdel-Gawad, Mahmoud; Elsobky, Emad; Shalaby, Mahmoud M; Abd-Elhameed, Mohamed; Abdel-Rahim, Mona; Ali-El-Dein, Bedeir

2016-12-01

The role of heavy metals and trace elements (HMTE) in the development of some cancers has been previously reported. Bladder carcinoma is a frequent malignancy of the urinary tract. The most common risk factors for bladder cancer are exposure to industrial carcinogens, cigarette smoking, gender, and possibly diet. The aim of this study was to evaluate HTME concentrations in the cancerous and adjacent non-cancerous tissues and compare them with those of normal cadaveric bladder. This prospective study included 102 paired samples of full-thickness cancer and adjacent non-cancerous bladder tissues of radical cystectomy (RC) specimens that were histologically proven as invasive bladder cancer (MIBC). We used 17 matched controls of non-malignant bladder tissue samples from cadavers. All samples were processed and evaluated for the concentration of 22 HMTE by using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Outcome analysis was made by the Mann-Whitney U, chi-square, Kruskal-Wallis, and Wilcoxon signed ranks tests. When compared with cadaveric control or cancerous, the adjacent non-cancerous tissue had higher levels of six elements (arsenic, lead, selenium, strontium, zinc, and aluminum), and when compared with the control alone, it had a higher concentration of calcium, cadmium, chromium, potassium, magnesium, and nickel. The cancerous tissue had a higher concentration of cadmium, lead, chromium, calcium, potassium, phosphorous, magnesium, nickel, selenium, strontium, and zinc than cadaveric control. Boron level was higher in cadaveric control than cancerous and adjacent non-cancerous tissue. Cadmium level was higher in cancerous tissue with node-positive than node-negative cases. The high concentrations of cadmium, lead, chromium, nickel, and zinc, in the cancerous together with arsenic in the adjacent non-cancerous tissues of RC specimens suggest a pathogenic role of these elements in BC. However, further work-up is needed to support this conclusion by the application of these HMTE on BC cell lines.

Biomarker Levels of Toxic Metals among Asian Populations in the United States: NHANES 2011–2012

PubMed Central

Awata, Hiroshi; Linder, Stephen; Mitchell, Laura E.; Delclos, George L.

2016-01-01

Introduction: The Centers for Disease Control and Prevention (CDC) recently found that Asians have considerably higher biomarker levels of cadmium, lead, mercury, and arsenic than whites, blacks, Mexican Americans, and other Hispanics in the United States. Objective: Our goal was to further evaluate the higher metal biomarker levels among Asians. Methods: Biomarker data (blood cadmium, blood lead, blood mercury, urinary total arsenic, and urinary dimethylarsinic acic) from individuals ≥ 6 years of age were obtained from the 2011–2012 National Health and Nutrition Examination Survey (NHANES). We compared geometric mean levels of these five metal biomarkers in Asians with those of four other NHANES race/ethnic groups (white, black, Mexican American, and other Hispanic), and across three Asian subgroups (Chinese, Asian Indian, and other Asian). We also evaluated associations between biomarker levels and sociodemographic, physical, dietary, and behavioral covariates across the Asian subgroups. Results: Asians had significantly higher levels of all five metal biomarkers than other race/ethnic groups (p < 0.05), regardless of sociodemographic, physical, dietary, behavioral, or geographic characteristics. We also found variations in biomarker levels across the Asian subgroups. In general, Asian Indians had lower levels than the other two Asian subgroups, except for blood lead. The following characteristics were found to be significant predictors of several biomarker levels: sex, age, education, birthplace, smoking, and fish consumption. Conclusions: Overall, the Asian group had the highest geometric mean biomarker levels for all of the five metal variables. Furthermore, we provided evidence that significant variations in the biomarker levels are present across the Asian subgroups in the United States. Citation: Awata H, Linder S, Mitchell LE, Delclos GL. 2017. Biomarker levels of toxic metals among Asian populations in the United States: NHANES 2011–2012. Environ Health Perspect 125:306–313; http://dx.doi.org/10.1289/EHP27 PMID:27517362

Prevalence and associated demographic characteristics of exposure to multiple metals and their species in human populations: The United States NHANES, 2007-2012.

PubMed

Shim, Youn K; Lewin, Michael D; Ruiz, Patricia; Eichner, June E; Mumtaz, Moiz M

2017-01-01

Lead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As) are among the top 10 pollutants of global health concern. Studies have shown that exposures to these metals produce severe adverse effects. However, the mechanisms underlying these effects, particularly joint toxicities, are poorly understood in humans. The objective of this investigation was to identify and characterize prevalent combinations of these metals and their species in the U.S. NHANES population to provide background data for future studies of potential metal interactions. Exposure was defined as urine or blood levels ≥ medians of the NHANES 2007-2012 participants ≥6 years (n = 7408). Adjusted-odds ratios (adj-OR) and 95% confidence intervals were determined for covariates (age, gender, and race/ethnicity, cotinine and body mass index). Species-specific analysis was also conducted for As and Hg including iAs (urinary arsenous acid and/or arsenic acid), met-iAs (urinary monomethylarsonic acid and/or dimethylarsinic acid), and oHg (blood methyl-mercury and/or ethyl-mercury). For combinations of As and Hg species, age- and gender-specific prevalence was determined among NHANES 2011-2012 participants (n = 2342). Data showed that approximately 49.3% of the population contained a combination of three or more metals. The most prevalent unique specific combinations were Pb/Cd/Hg/As, Pb/Cd/Hg, and Pb/Cd. Age was consistently associated with these combinations: adj-ORs ranged from 10.9 (Pb/Cd) to 11.2 (Pb/Cd/Hg/As). Race/ethnicity was significant for Pb/Cd/Hg/As. Among women of reproductive age, frequency of oHg/iAs/met-iAS and oHg/met-iAs was 22.9 and 40.3%, respectively. These findings may help prioritize efforts to assess joint toxicities and their impact on public health.

Lipid encapsulation of arsenic trioxide attenuates cytotoxicity and allows for controlled anticancer drug release.

PubMed

Chen, Haimei; MacDonald, Robert C; Li, Shuyou; Krett, Nancy L; Rosen, Steven T; O'Halloran, Thomas V

2006-10-18

Arsenic trioxide (ATO, As2O3) is emerging as a front line agent for treatment of acute promyelocytic leukemia with giving a complete remission rate of 83-95%. ATO also shows significant activity in relapsed/refactory multiple myeloma; however, efforts to expand clinical utility to other cancers have been limited by its toxicity profile at higher doses. New bioavailable, liposome encapsulated As(III) materials exhibit a significantly attenuated cytotoxicity that undergoes pH-triggered release of an active drug. The arsenic drugs are loaded into 100-nm-scale liposomes at high concentration (>270 mM) and excellent retention (shelf life > 6 months at 4 degrees C), as determined by inductively coupled plasma optical emission spectroscopy (ICP-OES), transmission electron microscopy (TEM), and energy-dispersive X-ray (EDX) diffraction. In the loading mechanism, arsenous acid crosses the bilayer membrane in exchange for acetic acid and an insoluble transitional metal (e.g., Ni2+, Co2+) arsenite salt is formed. The resultant liposomal arsenic nanoparticles appear to be stable in physiological situations but release the drug cargo in a lower pH environment, as encountered in intracellular endosomes. These drugs exhibit attenuated cytotoxicities against human lymphoma tumor cells compared with that of free As2O3. Controlled release of arsenic drugs, and hence control of toxicity, is feasible with this system. The results demonstrate that cytotoxicity can be controlled via transitions of the inorganic drug between solid and solution phases and suggest a mechanism for further improvement of the risk/benefit ratio of As2O3 in treatment of a variety of cancers.

In Vivo Exposure to Inorganic Arsenic Alters Differentiation-Specific Gene Expression of Adipose-Derived Mesenchymal Stem/Stromal Cells in C57BL/6J Mouse Model

PubMed Central

Shearer, Joseph J.; Figueiredo Neto, Manoel; Umbaugh, C. Samuel; Figueiredo, Marxa L.

2017-01-01

Abstract The number of mesenchymal stem cell (MSC) therapeutic modalities has grown in recent years. Adipose-derived mesenchymal stem/stromal cells (ASCs) can be isolated and expanded relatively easily as compared with their bone-marrow counterparts, making them a particularly promising source of MSCs. And although the biological mechanisms surrounding ASCs are actively being investigated, little is known about the effects that in vivo environmental exposures might have on their ability to properly differentiate. Therefore, we hypothesized that ASCs isolated from mice exposed to inorganic arsenic (iAs) would have an altered response towards adipogenic, osteogenic, and/or chondrogenic differentiation. To test this hypothesis, C57BL/6J male mice were provided drinking water containing 0, 300, or 1000 ppb iAs. ASCs were then isolated and differentiated, which was assessed by immunocytochemistry and real-time quantitative PCR (RT-qPCR). Our results showed that total urinary arsenic equilibrated within 1 week of exposure to iAs and was maintained throughout the study. ASCs isolated from each exposure group maintained differentiation capabilities for each lineage. The magnitude of differentiation-specific gene expression, however, appeared to be concentration dependent. For osteogenesis and chondrogenesis, differentiation-specific gene expression decreased, whereas adipogenesis showed a biphasic response with an initial decrease followed by an increase in adipogenic-related gene expression following iAs exposure. These results suggest that the level in which differentiation-specific genes are induced within these stromal cells might be sensitive to environmental contaminants. These findings highlight the need to take into account potential environmental exposures prior to selecting stromal cell donors, so ASCs can achieve optimal efficiency in regenerative therapy applications. PMID:28206643

DOSE-RESPONSE STUDIES OF SODIUM ARSENITE IN THE SKIN OF K6/ODC TRANSGENIC MOUSE

EPA Science Inventory

It has previously been observed that chronic exposure to inorganic arsenic and/or its metabolites increase(s) tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, gene expression profiles w...

EXPRESSON OF AS3MT ALTERS TRANSCRIPTIONAL PROFILES IN HUMAN UROTHELIAL CELLS EXPOSED TO ARSENITE

EPA Science Inventory

Inorganic arsenic (iAs) is an environmental toxin and human carcinogen. The enzymatic methylation of iAs that is catalyzed by As (3+ oxidation state)-methyltransferase (AS3MT) generates reactive methyl-As intermediates that may contribute to the toxic or carcinogenic effects of i...

Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves

NASA Astrophysics Data System (ADS)

Dixit, Garima; Singh, Amit Pal; Kumar, Amit; Dwivedi, Sanjay; Deeba, Farah; Kumar, Smita; Suman, Shankar; Adhikari, Bijan; Shukla, Yogeshwar; Trivedi, Prabodh Kumar; Pandey, Vivek; Tripathi, Rudra Deo

2015-11-01

Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress.

Shotgun metabolomic approach based on mass spectrometry for hepatic mitochondria of mice under arsenic exposure.

PubMed

García-Sevillano, M A; García-Barrera, T; Navarro, F; Montero-Lobato, Z; Gómez-Ariza, J L

2015-04-01

Mass spectrometry (MS)-based toxicometabolomics requires analytical approaches for obtaining unbiased metabolic profiles. The present work explores the general application of direct infusion MS using a high mass resolution analyzer (a hybrid systems triple quadrupole-time-of-flight) and a complementary gas chromatography-MS analysis to mitochondria extracts from mouse hepatic cells, emphasizing on mitochondria isolation from hepatic cells with a commercial kit, sample treatment after cell lysis, comprehensive metabolomic analysis and pattern recognition from metabolic profiles. Finally, the metabolomic platform was successfully checked on a case-study based on the exposure experiment of mice Mus musculus to inorganic arsenic during 12 days. Endogenous metabolites alterations were recognized by partial least squares-discriminant analysis. Subsequently, metabolites were identified by combining MS/MS analysis and metabolomics databases. This work reports for the first time the effects of As-exposure on hepatic mitochondria metabolic pathways based on MS, and reveals disturbances in Krebs cycle, β-oxidation pathway, amino acids degradation and perturbations in creatine levels. This non-target analysis provides extensive metabolic information from mitochondrial organelle, which could be applied to toxicology, pharmacology and clinical studies.

Population Structure and Abundance of Arsenite-Oxidizing Bacteria along an Arsenic Pollution Gradient in Waters of the Upper Isle River Basin, France▿ †

PubMed Central

Quéméneur, Marianne; Cébron, Aurélie; Billard, Patrick; Battaglia-Brunet, Fabienne; Garrido, Francis; Leyval, Corinne; Joulian, Catherine

2010-01-01

Denaturing gradient gel electrophoresis (DGGE) and quantitative real-time PCR (qPCR) were successfully developed to monitor functional aoxB genes as markers of aerobic arsenite oxidizers. DGGE profiles showed a shift in the structure of the aoxB-carrying bacterial population, composed of members of the Alpha-, Beta- and Gammaproteobacteria, depending on arsenic (As) and Eh levels in Upper Isle River Basin waters. The highest aoxB gene densities were found in the most As-polluted oxic surface waters but without any significant correlation with environmental factors. Arsenite oxidizers seem to play a key role in As mobility in As-impacted waters. PMID:20453153

Identifying arsenic trioxide (ATO) functions in leukemia cells by using time series gene expression profiles.

PubMed

Yang, Hong; Lin, Shan; Cui, Jingru

2014-02-10

Arsenic trioxide (ATO) is presently the most active single agent in the treatment of acute promyelocytic leukemia (APL). In order to explore the molecular mechanism of ATO in leukemia cells with time series, we adopted bioinformatics strategy to analyze expression changing patterns and changes in transcription regulation modules of time series genes filtered from Gene Expression Omnibus database (GSE24946). We totally screened out 1847 time series genes for subsequent analysis. The KEGG (Kyoto encyclopedia of genes and genomes) pathways enrichment analysis of these genes showed that oxidative phosphorylation and ribosome were the top 2 significantly enriched pathways. STEM software was employed to compare changing patterns of gene expression with assigned 50 expression patterns. We screened out 7 significantly enriched patterns and 4 tendency charts of time series genes. The result of Gene Ontology showed that functions of times series genes mainly distributed in profiles 41, 40, 39 and 38. Seven genes with positive regulation of cell adhesion function were enriched in profile 40, and presented the same first increased model then decreased model as profile 40. The transcription module analysis showed that they mainly involved in oxidative phosphorylation pathway and ribosome pathway. Overall, our data summarized the gene expression changes in ATO treated K562-r cell lines with time and suggested that time series genes mainly regulated cell adhesive. Furthermore, our result may provide theoretical basis of molecular biology in treating acute promyelocytic leukemia. Copyright © 2013 Elsevier B.V. All rights reserved.

Use of urinary 13,14, dihydro-15-keto-prostaglandin F2α (PGFM) concentrations to diagnose pregnancy and predict parturition in the giant panda (Ailuropoda melanolecua)

PubMed Central

Brown, Janine L.; Kersey, David C.; Snyder, Rebecca J.; Durrant, Barbara S.; Kouba, Andrew J.

2018-01-01

Pregnancy determination is difficult in the giant panda (Ailuropoda melanolecua), representing a challenge for ex situ conservation efforts. Research in other species experiencing pseudopregnancy indicates that urinary/fecal concentrations of 13,14, dihydro-15-keto-prostaglandin F2α (PGFM) can accurately determine pregnancy status. Our objective was to determine if urinary PGFM concentrations are associated with pregnancy status in the giant panda. Urinary PGFM concentrations were measured in female giant pandas (n = 4) throughout gestation (n = 6) and pseudopregnancy (n = 4) using a commercial enzyme immunoassay. Regardless of pregnancy status, PGFM excretion followed a predictable pattern: 1) baseline concentrations for 11–19 weeks following ovulation; 2) a modest, initial peak 14–36 days after the start of the secondary urinary progestagen rise; 3) a subsequent period of relatively low concentrations; and 4) a large, terminal peak at the end of the luteal phase. Pregnant profiles were distinguished by an earlier initial peak (P = 0.024), higher inter-peak concentrations (P < 0.001), and a larger terminal peak (P = 0.003) compared to pseudopregnancy profiles. Parturition occurred 23 to 25 days from the initial PGFM surge and within 24 hours of the start of the terminal increase. These pattern differences indicate that urinary PGFM monitoring can be used to predict pregnancy status and time parturition in the giant panda. Furthermore, this is the only species known to exhibit a significant PGFM increase during pseudopregnancy, suggesting a unique physiological mechanism for regulating the end of the luteal phase in the giant panda. PMID:29718929

Urinary metabolomic profiling in rats exposed to dietary di(2-ethylhexyl) phthalate (DEHP) using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS).

PubMed

Dong, Xinwen; Zhang, Yunbo; Dong, Jin; Zhao, Yue; Guo, Jipeng; Wang, Zhanju; Liu, Mingqi; Na, Xiaolin; Wang, Cheng

2017-07-01

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental chemical with widespread nonoccupational human exposure through multiple ways. Although considerable efforts have been invested to investigate mechanisms of DEHP toxicity, the key metabolic biomarkers of DEHP toxicity remain to be identified. The aim of this study was to assess the urinary metabonomics of dietary DEHP in rats using the technique of ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). Fourteen female Wistar rats were divided into two groups and given increasing dietary doses of DEHP for 30 consecutive days. The urinary metabolite profile was studied using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) enabled clusters to be clearly separated. Eleven principal urinary metabolites were identified as contributing to the clusters. The clusters in the positive electrospray ionization (ESI) mode were xanthurenic acid, kynurenic acid, nonate, N6-methyladenosine, and L-isoleucyl-L-proline. The clusters in the negative ESI mode were hippuric acid, tetrahydrocortisol, citric acid, phenylpropionylglycine, cPA(18:2(9Z, 12Z)/0:0), and LysoPC(14:1(9Z)). The urinary metabonomic changes indicated that exposure to dietary DEHP can affect energy-related metabolism, liver and renal function, fatty acid metabolism, and cause DNA damage in rats. The findings of this study on the urinary metabolites and metabolic pathways of DEHP may form the basis for future studies on the mechanisms of toxicity of this commonly found environmental chemical.

Urinary extracellular vesicles for RNA extraction: optimization of a protocol devoid of prokaryote contamination.

PubMed

Tataruch-Weinert, Dorota; Musante, Luca; Kretz, Oliver; Holthofer, Harry

2016-01-01

Urinary extracellular vesicles (UEVs) represent an ideal platform for biomarker discovery. They carry different types of RNA species, and reported profile discrepancies related to the presence/absence of 18s and 28s rRNA remain controversial. Moreover, sufficient urinary RNA yields and respective quality RNA profiles are still to be fully established. UEVs were enriched by hydrostatic filtration dialysis, and RNA content was extracted using 7 different commercially available techniques. RNA quantity was assessed using spectrophotometry and fluorometry, whilst RNA quality was determined by capillary electrophoresis. The presence of prokaryotic transcriptome was stressed when cellular RNA, as a control, was spiked into the UEVs samples before RNA extraction. The presence of bacteria in hydrostatic filtration dialysis above 1,000 kDa molecular weight cut-off and in crude urine was confirmed with growth media plates. The efficiency in removing urinary bacteria was evaluated by differential centrifugation, filtration (0.22 µm filters) and chemical pretreatment (water purification tablet). For volumes of urine >200 ml, the chemical treatment provides ease of handling without affecting vesicle integrity, protein and RNA profiles. This protocol was selected to enrich RNA with 7 methods, and its respective quality and quantity were assessed. The results were given as follows: (a) Fluorometry gave more repeatability and reproducibility than spectrophotometry to assess the RNA yields, (b) UEVs were enriched with small RNA, (c) Ribosomal RNA peaks were not observed for any RNA extraction method used and (d) RNA yield was higher for column-based method designed for urinary exosome, whilst the highest relative microRNA presence was obtained using TRIzol method. Our results show that the presence of bacteria can lead to misidentification in the electrophoresis peaks. Fluorometry is more reliable than spectrophotometry. RNA isolation method must be selected in conjunction with appropriate UEV collection procedure. We also suggested that a minimum 250 ml of urine should be processed to gather enough RNA for robust quantification, qualification and downstream analysis.

Urinary extracellular vesicles for RNA extraction: optimization of a protocol devoid of prokaryote contamination

PubMed Central

Tataruch-Weinert, Dorota; Musante, Luca; Kretz, Oliver; Holthofer, Harry

2016-01-01

Background Urinary extracellular vesicles (UEVs) represent an ideal platform for biomarker discovery. They carry different types of RNA species, and reported profile discrepancies related to the presence/absence of 18s and 28s rRNA remain controversial. Moreover, sufficient urinary RNA yields and respective quality RNA profiles are still to be fully established. Methods UEVs were enriched by hydrostatic filtration dialysis, and RNA content was extracted using 7 different commercially available techniques. RNA quantity was assessed using spectrophotometry and fluorometry, whilst RNA quality was determined by capillary electrophoresis. Results The presence of prokaryotic transcriptome was stressed when cellular RNA, as a control, was spiked into the UEVs samples before RNA extraction. The presence of bacteria in hydrostatic filtration dialysis above 1,000 kDa molecular weight cut-off and in crude urine was confirmed with growth media plates. The efficiency in removing urinary bacteria was evaluated by differential centrifugation, filtration (0.22 µm filters) and chemical pretreatment (water purification tablet). For volumes of urine >200 ml, the chemical treatment provides ease of handling without affecting vesicle integrity, protein and RNA profiles. This protocol was selected to enrich RNA with 7 methods, and its respective quality and quantity were assessed. The results were given as follows: (a) Fluorometry gave more repeatability and reproducibility than spectrophotometry to assess the RNA yields, (b) UEVs were enriched with small RNA, (c) Ribosomal RNA peaks were not observed for any RNA extraction method used and (d) RNA yield was higher for column-based method designed for urinary exosome, whilst the highest relative microRNA presence was obtained using TRIzol method. Conclusion Our results show that the presence of bacteria can lead to misidentification in the electrophoresis peaks. Fluorometry is more reliable than spectrophotometry. RNA isolation method must be selected in conjunction with appropriate UEV collection procedure. We also suggested that a minimum 250 ml of urine should be processed to gather enough RNA for robust quantification, qualification and downstream analysis. PMID:27345058

Dietary micronutrient intake and its relationship with arsenic metabolism in Mexican women

PubMed Central

López-Carrillo, Lizbeth; Gamboa-Loira, Brenda; Becerra, Wendy; Hernández-Alcaraz, César; Hernández-Ramírez, Raúl Ulises; Gandolfi, A. Jay; Franco-Marina, Francisco; Cebrián, Mariano E.

2017-01-01

Introduction Concentrations of inorganic arsenic (iAs) metabolites in urine present intra-and interindividual variations, which are determined not only by the magnitude of exposure to iAs, but also by differences in genetic, environmental and dietary factors. Objective To evaluate whether differences in dietary intake of selected micronutrients are associated with the metabolism of iAs. Methods The intake of 21 micronutrients was estimated for 1027 women living in northern Mexico using a food frequency questionnaire. Concentration of urinary metabolites of iAs was determined by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and the proportion of iAs metabolites was calculated (%iAs, monomethylarsonic acid [%MMA] and dimethylarsinic acid [%DMA]), as well as ratios corresponding to the first (MMA/iAs), second (DMA/MMA) and total methylation (DMA/iAs). Results After adjustment for covariates, it was found that methionine, choline, folate, vitamin B12, Zn, Se and vitamin C favor elimination of iAs mainly by decreasing the %MMA and/or increasing %DMA in urine. Conclusions Our results confirm that diet contributes to the efficiency of iAs elimination. Further studies are needed to assess the feasibility of dietary interventions that modulate the metabolism of iAs and the consequent risk of diseases related to its exposure. PMID:27565879

Prenatal Heavy Metal Exposure and Adverse Birth Outcomes in Myanmar: A Birth-Cohort Study.

PubMed

Wai, Kyi Mar; Mar, Ohn; Kosaka, Satoko; Umemura, Mitsutoshi; Watanabe, Chiho

2017-11-03

Arsenic, cadmium and lead are well-known environmental contaminants, and their toxicity at low concentration is the target of scientific concern. In this study, we aimed to identify the potential effects of prenatal heavy metal exposure on the birth outcomes among the Myanmar population. This study is part of a birth-cohort study conducted with 419 pregnant women in the Ayeyarwady Division, Myanmar. Face-to-face interviews were performed using a questionnaire, and maternal spot urine samples were collected at the third trimester. Birth outcomes were evaluated at delivery during the follow up. The median values of adjusted urinary arsenic, cadmium, selenium and lead concentration were 74.2, 0.9, 22.6 and 1.8 μg/g creatinine, respectively. Multivariable logistic regression revealed that prenatal cadmium exposure (adjusted odds ratio (OR) = 1.10; 95% confidence interval (CI): 1.01-1.21; p = 0.043), gestational age (adjusted OR = 0.83; 95% CI: 0.72-0.95; p = 0.009) and primigravida mothers (adjusted OR = 4.23; 95% CI: 1.31-13.65; p = 0.016) were the predictors of low birth weight. The present study identified that Myanmar mothers were highly exposed to cadmium. Prenatal maternal cadmium exposure was associated with an occurrence of low birth weight.

Dietary micronutrient intake and its relationship with arsenic metabolism in Mexican women.

PubMed

López-Carrillo, Lizbeth; Gamboa-Loira, Brenda; Becerra, Wendy; Hernández-Alcaraz, César; Hernández-Ramírez, Raúl Ulises; Gandolfi, A Jay; Franco-Marina, Francisco; Cebrián, Mariano E

2016-11-01

Concentrations of inorganic arsenic (iAs) metabolites in urine present intra- and interindividual variations, which are determined not only by the magnitude of exposure to iAs, but also by differences in genetic, environmental and dietary factors. To evaluate whether differences in dietary intake of selected micronutrients are associated with the metabolism of iAs. The intake of 21 micronutrients was estimated for 1027 women living in northern Mexico using a food frequency questionnaire. Concentration of urinary metabolites of iAs was determined by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and the proportion of iAs metabolites was calculated (%iAs, monomethylarsonic acid [%MMA] and dimethylarsinic acid [%DMA]), as well as ratios corresponding to the first (MMA/iAs), second (DMA/MMA) and total methylation (DMA/iAs). After adjustment for covariates, it was found that methionine, choline, folate, vitamin B12, Zn, Se and vitamin C favor elimination of iAs mainly by decreasing the %MMA and/or increasing %DMA in urine. Our results confirm that diet contributes to the efficiency of iAs elimination. Further studies are needed to assess the feasibility of dietary interventions that modulate the metabolism of iAs and the consequent risk of diseases related to its exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

Urinary tract infections in patients with spinal cord injuries.

PubMed

D'Hondt, Frederiek; Everaert, Karel

2011-12-01

Spinal cord injuries (SCI) result in different lower urinary tract dysfunctions. Because of both the disease and the bladder drainage method, urinary tract infections (UTIs) are one of the most frequent conditions seen in SCI patients. Diagnosis is not always easy due to lack of symptoms. Asymptomatic bacteriuria needs no treatment. If symptoms occur, antibiotherapy is indicated. Duration depends mainly on severity of illness and upper urinary tract or prostatic involvement. Choice of antibiotherapy should be based on local resistance profiles, but fluoroquinolones seems to be an adequate empirical treatment. Prevention of UTI is important, as lots of complications can be foreseen. Catheter care, permanent low bladder pressure and clean intermittent catheterization (CIC) with hydrophilic catheters are interventions that can prevent UTI. Probiotics might be useful, but data are limited.

¹H NMR-based metabolic profiling of naproxen-induced toxicity in rats.

PubMed

Jung, Jeeyoun; Park, Minhwa; Park, Hye Jin; Shim, Sun Bo; Cho, Yang Ha; Kim, Jinho; Lee, Ho-Sub; Ryu, Do Hyun; Choi, Donwoong; Hwang, Geum-Sook

2011-01-15

The dose-dependent perturbations in urinary metabolite concentrations caused by naproxen toxicity were investigated using ¹H NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic evaluation of naproxen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) of ¹H NMR from rat urine revealed a dose-dependent metabolic shift between the vehicle-treated control rats and rats treated with low-dose (10 mg/kg body weight), moderate-dose (50 mg/kg), and high-dose (100 mg/kg) naproxen, coinciding with their gastric damage scores after naproxen administration. The resultant metabolic profiles demonstrate that the naproxen-induced gastric damage exhibited energy metabolism perturbations that elevated their urinary levels of citrate, cis-aconitate, creatine, and creatine phosphate. In addition, naproxen administration decreased choline level and increased betaine level, indicating that it depleted the main protective constituent of the gastric mucosa. Moreover, naproxen stimulated the decomposition of tryptophan into kynurenate, which inhibits fibroblast growth factor-1 and delays ulcer healing. These findings demonstrate that ¹H NMR-based urinary metabolic profiling can facilitate noninvasive and rapid diagnosis of drug side effects and is suitable for elucidating possible biological pathways perturbed by drug toxicity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A new perspective on metals and other contaminants in fluoridation chemicals*

PubMed Central

Mullenix, Phyllis J

2014-01-01

Background: Fluoride additives contain metal contaminants that must be diluted to meet drinking water regulations. However, each raw additive batch supplied to water facilities does not come labeled with concentrations per contaminant. This omission distorts exposure profiles and the risks associated with accidents and routine use. Objectives: This study provides an independent determination of the metal content of raw fluoride products. Methods: Metal concentrations were analyzed in three hydrofluorosilicic acid (HFS) and four sodium fluoride (NaF) samples using inductively coupled plasma-atomic emission spectrometry. Arsenic levels were confirmed using graphite furnace atomic absorption analysis. Results: Results show that metal content varies with batch, and all HFS samples contained arsenic (4.9–56.0 ppm) or arsenic in addition to lead (10.3 ppm). Two NaF samples contained barium (13.3–18.0 ppm) instead. All HFS (212–415 ppm) and NaF (3312–3630 ppm) additives contained a surprising amount of aluminum. Conclusions: Such contaminant content creates a regulatory blind spot that jeopardizes any safe use of fluoride additives. PMID:24999851

[Translation and linguistic validation in classical Arabic of the urinary symptom profile (USP) questionnaire].

PubMed

Arabi, H; Bendeddouche, I; Khalfaoui, S; Louardi, N; Ameur, A; Lebreton, F; Amarenco, G

2013-04-01

The objective was to translate and linguistically validate in classical Arabic; the French version of the Urinary Symptom Profile (USP), the scale adapted to vesico-sphincter disorders. Prospective study of 30 patients suffering the vesico-sphincter disorders. The translation was obtained by the method: translation back-translation. Patients completed the final questionnaire on day 0 and day 15. The feasibility, acceptability, internal consistency using Cronbach's alpha and test-retest repeatability by the interclass correlation coefficient (ICC) with the confidence interval (CI) were studied. The sample consisted of 30 subjects including 20 men (66.6%) and 10 women (33.3%). The mean age was 48±18, 14 years ranging from 25 to 70 years. The questionnaire was feasible and acceptable. The Cronbach's alpha of the three dimensions, urinary stress incontinence, overactive bladder and voiding difficulties was respectively 0.9880, 0.9774 and 0.9683, respectively; the ICC was 0.9762 (95% CI: 0.9307-0.9919), 0.9558 (CI 95%: 0.8738-0.9849) and 0.9385 (95% CI: 0.8274-0.9789). The Arabic version of the classic USP had excellent internal consistency and excellent repeatability enable a full assessment of all urinary disorders and their severity. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

[Methods of use and behavior of cocaine addicts consulting medical-legal emergency units in Paris. Clinical aspects and urinary toxicology profile].

PubMed

Bécour, Bertrand; Menet, Marie-Claude; Questel, Frank; Guyon, François; Diamant-Berger, Odile

2003-03-01

Establish the epidemiological characteristics and urinary toxicological profiles of a population of cocaine addicts under police custody. A series of 60 cocaine addicts consulting the medico-legal emergency unit of the Hôtel-Dieu hospital in Paris was studied prospectively on the following elements: clinical characteristics, method of cocaine administration and association with other licit or illicit substances. Urinary toxicological analysis, using immuno-chemistry and chromatography linked to a mass spectrometer was systematically proposed to each patient. Half of the 17 to 26 year-old patients declared having consumed cocaine for the past 2 to 5 years. Inhalation of the vapours and the intravenous route were used more than the cigarette or nasal route. The majority of 26 to 35 year-olds were multi-drug addicted, generally associating cocaine, heroine and tobacco. Analysis of the urine provided an objective assessment of the cocaine consumption of these persons under police custody in Paris. Screening for urinary toxicity gives better knowledge on the consumption of addictive products by the person in whom urine was sampled. This study was conducted in cocaine addicts under police custody, and for the majority were social misfits. In this population, the consumption of crack by inhalation predominated.

Effect of age on toxicokinetics among human volunteers exposed to propylene glycol methyl ether (PGME).

PubMed

Hopf, Nancy B; Vernez, David; Berthet, Aurelie; Charriere, Nicole; Arnoux, Christine; Tomicic, Catherine

2012-05-20

Aging adults represent the fastest growing population segment in many countries. Physiological and metabolic changes in the aging process may alter how aging adults biologically respond to pollutants. In a controlled human toxicokinetic study (exposure chamber; 12 m³), aging volunteers (n=10; >58 years) were exposed to propylene glycol monomethyl ether (PGME, CAS no. 107-98-2) at 50 ppm for 6 h. The dose-dependent renal excretion of oxidative metabolites, conjugated and free PGME could potentially be altered by age. (1) Compare PGME toxicokinetic profiles between aging and young volunteers (20-25 years) and gender; (2) test the predictive power of a compartmental toxicokinetic (TK) model developed for aging persons against urinary PGME concentrations found in this study. Urine samples were collected before, during, and after the exposure. Urinary PGME was quantified by capillary GC/FID. Differences in urinary PGME profiles were not noted between genders but between age groups. Metabolic parameters had to be changed to fit the age adjusted TK model to the experimental results, implying a slower enzymatic pathway in the aging volunteers. For an appropriate exposure assessment, urinary total PGME should be quantified. Age is a factor that should be considered when biological limit values are developed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Metabolomic Profiling of Extracellular Vesicles and Alternative Normalization Methods Reveal Enriched Metabolites and Strategies to Study Prostate Cancer-Related Changes

PubMed Central

Puhka, Maija; Takatalo, Maarit; Nordberg, Maria-Elisa; Valkonen, Sami; Nandania, Jatin; Aatonen, Maria; Yliperttula, Marjo; Laitinen, Saara; Velagapudi, Vidya; Mirtti, Tuomas; Kallioniemi, Olli; Rannikko, Antti; Siljander, Pia R-M; af Hällström, Taija Maria

2017-01-01

Body fluids are a rich source of extracellular vesicles (EVs), which carry cargo derived from the secreting cells. So far, biomarkers for pathological conditions have been mainly searched from their protein, (mi)RNA, DNA and lipid cargo. Here, we explored the small molecule metabolites from urinary and platelet EVs relative to their matched source samples. As a proof-of-concept study of intra-EV metabolites, we compared alternative normalization methods to profile urinary EVs from prostate cancer patients before and after prostatectomy and from healthy controls. Methods: We employed targeted ultra-performance liquid chromatography-tandem mass spectrometry to profile over 100 metabolites in the isolated EVs, original urine samples and platelets. We determined the enrichment of the metabolites in the EVs and analyzed their subcellular origin, pathways and relevant enzymes or transporters through data base searches. EV- and urine-derived factors and ratios between metabolites were tested for normalization of the metabolomics data. Results: Approximately 1 x 1010 EVs were sufficient for detection of metabolite profiles from EVs. The profiles of the urinary and platelet EVs overlapped with each other and with those of the source materials, but they also contained unique metabolites. The EVs enriched a selection of cytosolic metabolites including members from the nucleotide and spermidine pathways, which linked to a number of EV-resident enzymes or transporters. Analysis of the urinary EVs from the patients indicated that the levels of glucuronate, D-ribose 5-phosphate and isobutyryl-L-carnitine were 2-26-fold lower in all pre-prostatectomy samples compared to the healthy control and post-prostatectomy samples (p < 0.05). These changes were only detected from EVs by normalization to EV-derived factors or with metabolite ratios, and not from the original urine samples. Conclusions: Our results suggest that metabolite analysis of EVs from different samples is feasible using a high-throughput platform and relatively small amount of sample material. With the knowledge about the specific enrichment of metabolites and normalization methods, EV metabolomics could be used to gain novel biomarker data not revealed by the analysis of the original EV source materials. PMID:29109780

Revisiting the biogeochemistry of arsenic in the Baltic Sea: Impact of anthropogenic activity.

PubMed

Li, Lei; Pohl, Christa; Ren, Jing-Ling; Schulz-Bull, Detlef; Cao, Xiu-Hong; Nausch, Günther; Zhang, Jing

2018-02-01

With the increase in anthropogenic environmental disruption, the behavior of arsenic in the Baltic Sea has received more scientific attention because of its complex forms and toxicity, and was re-visited to determine if there have been measurable changes recently. A cruise was conducted in 10-19 May 2011 to investigate the species and distribution of total dissolved inorganic arsenic (TDIAs: [TDIAs]=[As(V)]+[As(III)]) revealing links between the hydrographic dynamics and biological/chemical reactions in the Baltic Sea. In addition, long-term (2002-2010) time-series investigations of particulate arsenic in the Gotland Basin were also conducted in February every year for monitoring purposes. The behavior of TDIAs was non-conservative due to the removal and regeneration processes occurring in the Baltic Sea. Biological scavenging plays a dominant role as sink for TDIAs, with removal amount of 3.1±1.6nmol/L above the pycnocline of the Baltic Sea. Significant regeneration of TDIAs was observed below the pycnocline of the Baltic Sea, which was closely related to hypoxia. The decomposition of organic arsenic and release from the sediment by desorption of As-bearing Fe and Mn oxides were thought to be two major sources for TDIAs regeneration. The median concentration of TDIAs (8.4nmol/L) was much lower than in most marginal seas and oceans, including the near-bottom water around a chemical weapon dumpsite (13.9nmol/L). The hypoxia in the deep water contributed to the increase in As(III) concentrations based on the relationship between As(III)/TDIAs ratio and apparent oxygen utilization. If the difference of As(III) profiles (1981 and 2011) actually represents a long-term increase in As(III) concentrations and a shoaling of the As(III) chemocline, these factors could enhance the toxic effects and extend the residence time of arsenic and, hence, potentially have negative impacts on fisheries and ecosystem health in the Baltic Sea. Copyright © 2017 Elsevier B.V. All rights reserved.

Local Resistance Profiling of Ultra Shallow Junction Annealed with Combination of Spike Lamp and Laser Annealing Processes using Scanning Spreading Resistance Microscope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abo, Satoshi; Nishikawa, Kazuhisa; Ushigome, Naoya

2011-01-07

Local resistance profiles of ultra shallow boron and arsenic implanted into silicon with energies of 2.0 and 4.0 keV and doses of 2.0x10{sup 15} and 1.0x10{sup 15} ions/cm{sup 2} activated by a combination of conventional spike lamp and laser annealing processes were measured by scanning spreading resistance microscope (SSRM) with a depth resolution of less than 10 nm. The lowest local resistance at the low resistance region in 2.0 keV boron implanted silicon with 1050 deg. C spike lamp annealing followed by 0.35 kW/mm{sup 2} laser annealing was half of that without laser annealing. The lowest local resistance at themore » low resistance region in the arsenic implanted silicon activated by 1050 deg. C spike lamp annealing followed by 0.39 kW/mm{sup 2} laser annealing was 74% lower than that followed by 0.36 kW/mm{sup 2} laser annealing. The lowest local resistances at the low resistance regions in the arsenic implanted silicon with 0.36 and 0.39 kW/mm{sup 2} laser annealing followed by 1050 deg. C spike lamp annealing were 41 and 33% lower than those with spike lamp annealing followed by laser annealing. Laser annealing followed by spike lamp annealing could suppress the diffusion of the impurities and was suitable for making the ultra shallow and low resistance regions.« less

Metabolic stone composition in Egyptian children.

PubMed

Aggour, Ashraf; Ziada, Ali M; AbdelHamid, Ahmad Z; AbdelRahman, Sherif; Morsi, Ahmad

2009-04-01

The composition of urinary stones in children depends on socioeconomic conditions, geography and dietary habits. Pediatric urolithiasis remains endemic in developing countries. The aim of this study was to analyze stone composition in an Egyptian patient population. We analyzed prospectively urinary stones from 100 consecutive children (73 males, 27 females), aged 14 months to 12 years. The stones were located in the upper urinary tract in 78%, lower urinary tract in 19% and both in 3%. Male patients had more lower urinary tract stones. On presentation 67% had flank pain and 37% had hematuria. Stones were treated by open surgery in 69% of patients, shockwave lithotripsy in 20% and endoscopic extraction in 13%. The components of the upper urinary tract calculi were calcium oxalate (47%), ammonium acid urate (26%) and calcium carbonate (21%), whereas the main components of the lower urinary tract calculi were ammonium acid urate (27.2%), struvite (27.2%) and calcium carbonate (22.7%). Urinary tract infection was involved in the development of one third of the stones. Endemic stones were present in 17% of patients, and stones of metabolic origin in 15%. The etiology of stone formation remained unknown in one third of patients. The epidemiological profile of urinary stones in Egyptian children can now be considered intermediate between developing countries where dietary deficiencies are the main causes and developed countries where infectious and metabolic calculi are observed.

Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis

ClinicalTrials.gov

2017-02-02

Pseudomonas Infections; Pseudomonas Septicemia; Pseudomonas; Pneumonia; Pseudomonal Bacteraemia; Pseudomonas Urinary Tract Infection; Pseudomonas Gastrointestinal Tract Infection; Sepsis; Sepsis, Severe; Critically Ill

Biomarkers identified by urinary metabonomics for noninvasive diagnosis of nutritional rickets.

PubMed

Wang, Maoqing; Yang, Xue; Ren, Lihong; Li, Songtao; He, Xuan; Wu, Xiaoyan; Liu, Tingting; Lin, Liqun; Li, Ying; Sun, Changhao

2014-09-05

Nutritional rickets is a worldwide public health problem; however, the current diagnostic methods retain shortcomings for accurate diagnosis of nutritional rickets. To identify urinary biomarkers associated with nutritional rickets and establish a noninvasive diagnosis method, urinary metabonomics analysis by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis were employed to investigate the metabolic alterations associated with nutritional rickets in 200 children with or without nutritional rickets. The pathophysiological changes and pathogenesis of nutritional rickets were illustrated by the identified biomarkers. By urinary metabolic profiling, 31 biomarkers of nutritional rickets were identified and five candidate biomarkers for clinical diagnosis were screened and identified by quantitative analysis and receiver operating curve analysis. Urinary levels of five candidate biomarkers were measured using mass spectrometry or commercial kits. In the validation step, the combination of phosphate and sebacic acid was able to give a noninvasive and accurate diagnostic with high sensitivity (94.0%) and specificity (71.2%). Furthermore, on the basis of the pathway analysis of biomarkers, our urinary metabonomics analysis gives new insight into the pathogenesis and pathophysiology of nutritional rickets.

Aqueous extract of Carica papaya Linn. roots potentially attenuates arsenic induced biochemical and genotoxic effects in Wistar rats.

PubMed

Ojo, Oluwafemi Adeleke; Ojo, Adebola Busola; Awoyinka, Olayinka; Ajiboye, Basiru Olaitan; Oyinloye, Babatunji Emmanuel; Osukoya, Olukemi Adetutu; Olayide, Israel Idowu; Ibitayo, Adejoke

2018-04-01

In Africa, the fruit, leaf, seed and roots of Carica papaya Linn. are generally used to treat a variety of diseases such as malaria, cancer, and cardiovascular diseases. In this study, we evaluated the protective potentials of aqueous extract of C. papaya roots on arsenic-induced biochemical and genotoxic effects in Wistar rats. Rats were induced intraperitoneal with sodium arsenate (dissolved in distilled water at 3 mg/kg body weight) for 21 days and the animals were administered simultaneously with 200 mg/kg body weight vitamin C, 100 and 150 mg/kg body weight of the C. papaya Linn. root aqueous extract once daily for three weeks. Results obtained reveals that activities of plasma 8-OHdG, serum lipids concentration, atherogenic index (AI), coronary artery index (CRI), aspartate transaminase, alanine transaminase, alkaline phosphatase, total bilirubin levels were elevated significantly ( p  < 0.05) and catalase, glutathione peroxidase, superoxide dismutase, plasma hematological profile were progressively reduced ( p  < 0.05) in arsenic-alone exposed rats. Significant increase in the quantity of chromosomal aberrations (CA), micronuclei (MN) frequency, oxidative damages in the bone marrow cells from arsenic alone rats was observed. Though, mitotic index scores in these cells were progressively reduced (p < 0.05). In animals administered with aqueous extract of C. papaya roots and vitamin C, the altered parameters were significantly recovered towards the levels observed in normal control rats. These results suggest that aqueous C. papaya roots preparations might have therapeutic potential as a supplement that can be applied in arsenic poisoning.

Urinary pH as a Risk Factor for Stone Type

NASA Astrophysics Data System (ADS)

Sakhaee, Khashayar

2007-04-01

A high urinary pH is main risk factor for the calcium phosphate stone formation; however, its pathophysiologic mechanism has not been fully understood. The introduction of Topiramate in the treatment of various neurological disorders has been complicated by metabolic acidosis, significant hypocitraturia, elevated urinary pH, and calcium phosphate stone formation. This model provides a probe to investigate the pathophysiologic mechanism of calcium phosphate stone formation and perhaps to develop appropriate countermeasures in the future. On the other hand an unduly acidic urine predisposes one to uric acid nephrolithiasis. Our recent investigation linking low urinary pH, and defective renal ammoniagenesis to insulin resistance provides new knowledge to unfold the pathophysiology of uric acid nephrolithiasis. The metabolic profile leading to uric acid stone may emerge as one of the components of metabolic syndrome.

Uric acid nephrolithiasis: An update.

PubMed

Cicerello, Elisa

2018-04-01

Uric acid nephrolithiasis appears to increase in prevalence. While a relationship between uric acid stones and low urinary pH has been for long known, additional association with various metabolic conditions and pathophysiological basis has recently been elucidated. Some conditions such as diabetes and metabolic syndrome disease, excessive dietary intake, and increased endogenous uric acid production and/or defect in ammoniagenesis are associated with low urinary pH. In addition, the phenomenon of global warming could result in an increase in areas with greater climate risk for uric acid stone formation. There are three therapeutic steps to be taken for management of uric acid stones: identification of urinary pH profiles, assessment of urinary volume status, and identification of disorders leading to excessive uric acid production. However, the most important factor for uric acid stone formation is acid urinary pH, which is a prerequisite for uric acid precipitation. This article reviews recent insights into the pathophysiology of uric acid stones and their management.

In vitro assessment of arsenic mobility in historical mine waste dust using simulated lung fluid.

PubMed

Martin, Rachael; Dowling, Kim; Nankervis, Scott; Pearce, Dora; Florentine, Singarayer; McKnight, Stafford

2018-06-01

Exposure studies have linked arsenic (As) ingestion with disease in mining-affected populations; however, inhalation of mine waste dust as a pathway for pulmonary toxicity and systemic absorption has received limited attention. A biologically relevant extractant was used to assess the 24-h lung bioaccessibility of As in dust isolated from four distinct types of historical gold mine wastes common to regional Victoria, Australia. Mine waste particles less than 20 µm in size (PM 20 ) were incubated in a simulated lung fluid containing a major surface-active component found in mammalian lungs, dipalmitoylphosphatidylcholine. The supernatants were extracted, and their As contents measured after 1, 2, 4, 8 and 24 h. The resultant As solubility profiles show rapid dissolution followed by a more modest increasing trend, with between 75 and 82% of the total 24-h bioaccessible As released within the first 8 h. These profiles are consistent with the solubility profile of scorodite, a secondary As-bearing phase detected by X-ray diffraction in one of the investigated waste materials. Compared with similar studies, the cumulative As concentrations released at the 24-h time point were extremely low (range 297 ± 6-3983 ± 396 µg L -1 ), representing between 0.020 ± 0.002 and 0.036 ± 0.003% of the total As in the PM 20 .

Metabolomics Approach to Male Lower Urinary Tract Symptoms: Identification of Possible Biomarkers and Potential Targets for New Treatments.

PubMed

Mitsui, Takahiko; Kira, Satoru; Ihara, Tatsuya; Sawada, Norifumi; Nakagomi, Hiroshi; Miyamoto, Tatsuya; Shimura, Hiroshi; Yokomichi, Hiroshi; Takeda, Masayuki

2018-05-01

We identified metabolites using a metabolomics approach and investigated the association between these metabolites and lower urinary tract symptoms. We used a 24-hour bladder diary and I-PSS (International Prostate Symptom Score) to assess micturition behavior and lower urinary tract symptoms in 58 male patients without apparent neurological disease. Lower urinary tract symptoms were defined as a total I-PSS score of 8 or greater. Patients with a score of 7 or less were placed in the control group. A comprehensive study of plasma metabolites was also performed by capillary electrophoresis time-of-flight mass spectrometry. Metabolites were compared between the lower urinary tract symptoms and control groups using the Mann-Whitney U test. Biomarkers of male lower urinary tract symptoms from the metabolites were analyzed using multivariable logistic regression analysis to determine the OR. Of the 58 men 32 were in the lower urinary tract symptoms group and the remaining 26 were in the control group. The 24-hour bladder diary showed that nocturnal urine volume, 24-hour micturition frequency, nocturnal micturition frequency and the nocturia index were significantly higher in the lower urinary tract symptoms group. Metabolomics analysis identified 60 metabolites from patient plasma. Multivariate analysis revealed that increased glutamate and decreased arginine, asparagine and inosine monophosphate were significantly associated with lower urinary tract symptoms in males. Decreases in citrulline and glutamine could also be associated with male lower urinary tract symptoms. Male lower urinary tract symptoms may develop due to abnormal metabolic processes in some pathways. Potential new treatments for lower urinary tract symptoms can be developed by identifying changes in the amino acid profiles. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Impact of storage conditions on the urinary metabolomics fingerprint.

PubMed

Laparre, Jérôme; Kaabia, Zied; Mooney, Mark; Buckley, Tom; Sherry, Mark; Le Bizec, Bruno; Dervilly-Pinel, Gaud

2017-01-25

Urine stability during storage is essential in metabolomics to avoid misleading conclusions or erroneous interpretations. Facing the lack of comprehensive studies on urine metabolome stability, the present work performed a follow-up of potential modifications in urinary chemical profile using LC-HRMS on the basis of two parameters: the storage temperature (+4 °C, -20 °C, -80 °C and freeze-dried stored at -80 °C) and the storage duration (5-144 days). Both HILIC and RP chromatographies have been implemented in order to globally monitor the urinary metabolome. Using an original data processing associated to univariate and multivariate data analysis, our study confirms that chemical profiles of urine samples stored at +4 °C are very rapidly modified, as observed for instance for compounds such as:N-acetyl Glycine, Adenosine, 4-Amino benzoic acid, N-Amino diglycine, creatine, glucuronic acid, 3-hydroxy-benzoic acid, pyridoxal, l-pyroglutamic acid, shikimic acid, succinic acid, thymidine, trigonelline and valeryl-carnitine, while it also demonstrates that urine samples stored at -20 °C exhibit a global stability over a long period with no major modifications compared to -80 °C condition. This study is the first to investigate long term stability of urine samples and report potential modifications in the urinary metabolome, using both targeted approach monitoring individually a large number (n > 200) of urinary metabolites and an untargeted strategy enabling assessing for global impact of storage conditions. Copyright © 2016 Elsevier B.V. All rights reserved.