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Sample records for genes urinary arsenic

  1. Polymorphisms in cell cycle regulatory genes, urinary arsenic profile and urothelial carcinoma

    SciTech Connect

    Chung, C.-J.; Huang, C.-J.; Pu, Y.-S.; Su, C.-T.; Huang, Y.-K.; Chen, Y.-T.; Hsueh, Y.-M.

    2008-10-15

    Introduction: Polymorphisms in p53, p21 and CCND1 could regulate the progression of the cell cycle and might increase the susceptibility to inorganic arsenic-related cancer risk. The goal of our study was to evaluate the roles of cell cycle regulatory gene polymorphisms in the carcinogenesis of arsenic-related urothelial carcinoma (UC). Methods: A hospital-based case-controlled study was conducted to explore the relationships among the urinary arsenic profile, 8-hydroxydeoxyguanosine (8-OHdG) levels, p53 codon 72, p21 codon 31 and CCND1 G870A polymorphisms and UC risk. The urinary arsenic profile was determined using high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). 8-OHdG levels were measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP). Results: Subjects carrying the p21 Arg/Arg genotype had an increased UC risk (age and gender adjusted OR = 1.53; 95% CI, 1.02-2.29). However, there was no association of p53 or CCND1 polymorphisms with UC risk. Significant effects were observed in terms of a combination of the three gene polymorphisms and a cumulative exposure of cigarette smoking, along with the urinary arsenic profile on the UC risk. The higher total arsenic concentration, monomethylarsonic acid percentage (MMA%) and lower dimethylarsinic acid percentage (DMA%), possessed greater gene variant numbers, had a higher UC risk and revealed significant dose-response relationships. However, effects of urinary 8-OHdG levels combined with three gene polymorphisms did not seem to be important for UC risk. Conclusions: The results showed that the variant genotype of p21 might be a predictor of inorganic arsenic-related UC risk.

  2. Binational arsenic exposure survey: methodology and estimated arsenic intake from drinking water and urinary arsenic concentrations.

    PubMed

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

    2012-04-01

    The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.

  3. 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...

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

    SciTech Connect

    Chen, Wei-Jen; Huang, Ya-Li; Shiue, Horng-Sheng; Chen, Tzen-Wen; Lin, Yuh-Feng; Huang, Chao-Yuan; Lin, Ying-Chin; Han, Bor-Cheng; Hsueh, Yu-Mei

    2014-09-01

    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 recruited 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

  5. Profile of urinary arsenic metabolites during pregnancy.

    PubMed Central

    Hopenhayn, Claudia; Huang, Bin; Christian, Jay; Peralta, Cecilia; Ferreccio, Catterina; Atallah, Raja; Kalman, David

    2003-01-01

    Chronic exposure to inorganic arsenic (In-As) from drinking water is associated with different health effects, including skin, lung, bladder, and kidney cancer as well as vascular and possibly reproductive effects. In-As is metabolized through the process of methylation, resulting in the production and excretion of methylated species, mainly monomethylarsenate (MMA) and dimethylarsenate (DMA). Because a large percentage of the dose is excreted in urine, the distribution of urinary In-As, MMA, and DMA is considered a useful indicator of methylation patterns in human populations. Several factors affect these patterns, including sex and exposure level. In this study, we investigated the profile of urinary In-As, MMA, and DMA of pregnant women. Periodic urine samples were collected from early to late pregnancy among 29 pregnant women living in Antofagasta, Chile, who drank tap water containing 40 micro g/L In-As. The total urinary arsenic across four sampling periods increased with increasing weeks of gestation, from an initial mean value of 36.1 to a final value of 54.3 micro g/L. This increase was mainly due to an increase in DMA, resulting in lower percentages of In-As and MMA and a higher percentage of DMA. Our findings indicate that among women exposed to moderate arsenic from drinking water during pregnancy, changes occur in the pattern of urinary arsenic excretion and metabolite distribution. The toxicologic significance of this is not clear, given recent evidence suggesting that intermediate methylated species may be highly toxic. Nevertheless, this study suggests that arsenic metabolism changes throughout the course of pregnancy, which in turn may have toxicologic effects on the developing fetus. Key words: arsenic, arsenic metabolism, arsenic methylation, Chile, pregnancy, urinary arsenic. PMID:14644662

  6. Profile of urinary arsenic metabolites during pregnancy.

    PubMed

    Hopenhayn, Claudia; Huang, Bin; Christian, Jay; Peralta, Cecilia; Ferreccio, Catterina; Atallah, Raja; Kalman, David

    2003-12-01

    Chronic exposure to inorganic arsenic (In-As) from drinking water is associated with different health effects, including skin, lung, bladder, and kidney cancer as well as vascular and possibly reproductive effects. In-As is metabolized through the process of methylation, resulting in the production and excretion of methylated species, mainly monomethylarsenate (MMA) and dimethylarsenate (DMA). Because a large percentage of the dose is excreted in urine, the distribution of urinary In-As, MMA, and DMA is considered a useful indicator of methylation patterns in human populations. Several factors affect these patterns, including sex and exposure level. In this study, we investigated the profile of urinary In-As, MMA, and DMA of pregnant women. Periodic urine samples were collected from early to late pregnancy among 29 pregnant women living in Antofagasta, Chile, who drank tap water containing 40 micro g/L In-As. The total urinary arsenic across four sampling periods increased with increasing weeks of gestation, from an initial mean value of 36.1 to a final value of 54.3 micro g/L. This increase was mainly due to an increase in DMA, resulting in lower percentages of In-As and MMA and a higher percentage of DMA. Our findings indicate that among women exposed to moderate arsenic from drinking water during pregnancy, changes occur in the pattern of urinary arsenic excretion and metabolite distribution. The toxicologic significance of this is not clear, given recent evidence suggesting that intermediate methylated species may be highly toxic. Nevertheless, this study suggests that arsenic metabolism changes throughout the course of pregnancy, which in turn may have toxicologic effects on the developing fetus. Key words: arsenic, arsenic metabolism, arsenic methylation, Chile, pregnancy, urinary arsenic.

  7. Urinary excretion of arsenic following rice consumption.

    PubMed

    Meharg, A A; Williams, P N; Deacon, C M; Norton, G J; Hossain, M; Louhing, D; Marwa, E; Lawgalwi, Y; Taggart, M; Cascio, C; Haris, P

    2014-11-01

    Patterns of arsenic excretion were followed in a cohort (n = 6) eating a defined rice diet, 300 g per day d.wt. where arsenic speciation was characterized in cooked rice, following a period of abstinence from rice, and other high arsenic containing foods. A control group who did not consume rice were also monitored. The rice consumed in the study contained inorganic arsenic and dimethylarsinic acid (DMA) at a ratio of 1:1, yet the urine speciation was dominated by DMA (90%). At steady state (rice consumption/urinary excretion) ∼40% of rice derived arsenic was excreted via urine. By monitoring of each urine pass throughout the day it was observed that there was considerable variation (up to 13-fold) for an individual's total arsenic urine content, and that there was a time dependent variation in urinary total arsenic content. This calls into question the robustness of routinely used first pass/spot check urine sampling for arsenic analysis.

  8. Developmentally Restricted Genetic Determinants of Human Arsenic Metabolism: Association between Urinary Methylated Arsenic and CYT19 Polymorphisms in Children

    PubMed Central

    Meza, Maria Mercedes; Yu, Lizhi; Rodriguez, Yelitza Y.; Guild, Mischa; Thompson, David; Gandolfi, A. Jay; Klimecki, Walter T.

    2005-01-01

    We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb. We chose 23 polymorphic sites to test in the arsenic-exposed population. Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D:M). In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D:M ratios in the total population. Subsequent analysis of this association revealed that the association signal for the entire population was actually caused by an extremely strong association in only the children (7–11 years of age) between CYT19 genotype and D:M levels. With children removed from the analysis, no significant genetic association was observed in adults (18–79 years). The existence of a strong, developmentally regulated genetic association between CYT19 and arsenic metabolism carries import for both arsenic pharmacogenetics and arsenic toxicology, as well as for public health and governmental regulatory officials. PMID:15929903

  9. Urinary arsenic metabolites of subjects exposed to elevated arsenic present in coal in Shaanxi Province, China.

    PubMed

    Gao, Jianwei; Yu, Jiangping; Yang, Linsheng

    2011-06-01

    In contrast to arsenic (As) poisoning caused by naturally occurring inorganic arsenic-contaminated water consumption, coal arsenic poisoning (CAP) induced by elevated arsenic exposure from coal combustion has rarely been reported. In this study, the concentrations and distributions of urinary arsenic metabolites in 57 volunteers (36 subjects with skin lesions and 21 subjects without skin lesions), who had been exposed to elevated levels of arsenic present in coal in Changshapu village in the south of Shaanxi Province (China), were reported. The urinary arsenic species, including inorganic arsenic (iAs) [arsenite (iAsIII) and arsenate (iAsV)], monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV), were determined by high-performance liquid chromatography (HPLC) combined with inductively coupled plasma mass spectroscopy (ICP-MS). The relative distributions of arsenic species, the primary methylation index (PMI=MMAV/iAs) and the secondary methylation index (SMI=DMAV/MMAV) were calculated to assess the metabolism of arsenic. Subjects with skin lesions had a higher concentration of urinary arsenic and a lower arsenic methylation capability than subjects without skin lesions. Women had a significantly higher methylation capability of arsenic than men, as defined by a higher percent DMAV and SMI in urine among women, which was the one possible interpretation of women with a higher concentration of urinary arsenic but lower susceptibility to skin lesions. The findings suggested that not only the dose of arsenic exposure but also the arsenic methylation capability have an impact on the individual susceptibility to skin lesions induced by coal arsenic exposure.

  10. 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...

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

    PubMed Central

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

    2012-01-01

    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 individualswithout 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 (DMA) urinary concentrations, whereas wild type AS3MT rs11191439 had significantly lower levels of AsIII and MMA. Genetic polymorphisms GSTO and As3MT modify arsenic metabolism as evidenced by altered urinary arsenic excretion. PMID:22339537

  12. Association between GSTO2 polymorphism and the urinary arsenic profile in copper industry workers.

    PubMed

    Paiva, Leiliane; Hernández, Alba; Martínez, Valeria; Creus, Amadeu; Quinteros, Domingo; Marcos, Ricardo

    2010-07-01

    Two members of the recently identified Omega class glutathione S-transferase enzymes (GSTO1 and GSTO2) have been proposed to play a role in the response to arsenic exposure. Therefore, polymorphisms in these genes could be related with variations in the arsenic excretion profile and, consequently, with the individual response to chronic exposure. Exons and flanking regions of GSTO2 gene have been screened in two different ethnic groups (20 Europeans and 20 Chilean Indians), and the urinary arsenic patterns and the GSTO2 Asn142Asp polymorphism have been investigated in 207 copper mine workers occupationally exposed to arsenic. Three polymorphisms of GSTO2 already described were detected in Europeans and Chilean Indians, although with significant different allele frequencies. The genotyping for the Asn142Asp polymorphism revealed that almost no significant association exists between this change and the arsenic excretion profile. However, 142Asp change seems to be correlated with an increase in DMA excretion after age and total urinary arsenic adjustment (OR=3.61; P=0.05). Altogether, our findings indicate that ethnical differences should be taken into account for correlation studies between GST Omega polymorphisms and arsenic susceptibility, and that the 142Asp allozyme could modulate arsenic biotransformation and thereby arsenic toxicity.

  13. Urinary Arsenic and Insulin Resistance in US Adolescents

    PubMed Central

    Peng, Qing; Harlow, Siobán D.; Park, Sung Kyun

    2015-01-01

    Chronic arsenic exposure has been associated with increased diabetes risk in adults. Insulin resistance (IR) has been proposed as a mechanism of arsenic-related diabetes. Although limited evidence in adults found no association between arsenic and IR, the association in adolescents is largely unknown. We examined the association between urinary arsenic and insulin resistance in US adolescents. Eight hundred thirty five adolescents aged 12-19 years, with complete data on urinary arsenic (total arsenic, inorganic arsenic and dimethylarsenic acid (DMA)), fasting glucose, insulin and key covariates were identified from the National Health and Nutrition Examination Survey (NHANES) cycles 2003/2004 through 2009/2010. Generalized additive mixed models accounting for intra-cluster correlation arising from the complex survey design were used to estimate the association between the updated Homeostasis Model Assessment (HOMA2)-IR and each type of arsenic. After adjusting for potential confounders, including urinary creatinine, sociodemographic factors, BMI, waist circumference, and arsenobetaine, arsenic exposure was not associated with HOMA2-IR. Interquartile range increases in total arsenic, inorganic arsenic and DMA were associated with 1.5% (95% CI: -2.0, 5.2), 1.1% (95% CI: -1.5, 3.8) and 0.25% (95% CI: -2.3, 2.9) increases in HOMA2-IR, respectively. In conclusion, despite arsenic's association with diabetes in adults and potential role in insulin resistance, our findings do not support the hypothesis that arsenic exposure at levels common in the US contributes to insulin resistance in adolescents. Whether higher doses and longer exposure duration are required for appreciable influence on insulin resistance, or that arsenic does not act through insulin resistance to induce diabetes needs further investigation.1 PMID:25845984

  14. Urinary arsenic and insulin resistance in US adolescents.

    PubMed

    Peng, Qing; Harlow, Siobán D; Park, Sung Kyun

    2015-06-01

    Chronic arsenic exposure has been associated with increased diabetes risk in adults. Insulin resistance (IR) has been proposed as a mechanism of arsenic-related diabetes. Although limited evidence in adults found no association between arsenic and IR, the association in adolescents is largely unknown. We examined the association between urinary arsenic and insulin resistance in US adolescents. Eight hundred thirty five adolescents aged 12-19 years, with complete data on urinary arsenic (total arsenic, inorganic arsenic and dimethylarsenic acid (DMA)), fasting glucose, insulin and key covariates were identified from the National Health and Nutrition Examination Survey (NHANES) cycles 2003/2004 through 2009/2010. Generalized additive mixed models accounting for intra-cluster correlation arising from the complex survey design were used to estimate the association between the updated Homeostasis Model Assessment (HOMA2)-IR and each type of arsenic. After adjusting for potential confounders, including urinary creatinine, sociodemographic factors, BMI, waist circumference, and arsenobetaine, arsenic exposure was not associated with HOMA2-IR. Interquartile range increases in total arsenic, inorganic arsenic and DMA were associated with 1.5% (95% CI: -2.0, 5.2), 1.1% (95% CI: -1.5, 3.8) and 0.25% (95% CI: -2.3, 2.9) increases in HOMA2-IR, respectively. In conclusion, despite arsenic's association with diabetes in adults and potential role in insulin resistance, our findings do not support the hypothesis that arsenic exposure at levels common in the US contributes to insulin resistance in adolescents. Whether higher doses and longer exposure duration are required for appreciable influence on insulin resistance, or that arsenic does not act through insulin resistance to induce diabetes needs further investigation.

  15. Urinary arsenic profile affects the risk of urothelial carcinoma even at low arsenic exposure

    SciTech Connect

    Pu, Y.-S.; Yang, S.-M.; Huang, Y.-K.; Chung, C.-J.; Huang, Steven K.; Chiu, Allen Wen-Hsiang; Yang, M.-H.; Chen, C.-J.; Hsueh, Y.-M. . E-mail: ymhsueh@tmu.edu.tw

    2007-01-15

    Arsenic exposure is associated with an increased risk of urothelial carcinoma (UC). To explore the association between individual risk and urinary arsenic profile in subjects without evident exposure, 177 UC cases and 313 age-matched controls were recruited between September 2002 and May 2004 for a case-control study. Urinary arsenic species including the following three categories, inorganic arsenic (As{sup III} + As{sup V}), monomethylarsonic acid (MMA{sup V}) and dimethylarsinic acid (DMA{sup V}), were determined with high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Arsenic methylation profile was assessed by percentages of various arsenic species in the sum of the three categories measured. The primary methylation index (PMI) was defined as the ratio between MMA{sup V} and inorganic arsenic. Secondary methylation index (SMI) was determined as the ratio between DMA{sup V} and MMA{sup V}. Smoking is associated with a significant risk of UC in a dose-dependent manner. After multivariate adjustment, UC cases had a significantly higher sum of all the urinary species measured, higher percent MMA{sup V}, lower percent DMA{sup V}, higher PMI and lower SMI values compared with controls. Smoking interacts with the urinary arsenic profile in modifying the UC risk. Differential carcinogenic effects of the urinary arsenic profile, however, were seen more prominently in non-smokers than in smokers, suggesting that smoking is not the only major environmental source of arsenic contamination since the UC risk differs in non-smokers. Subjects who have an unfavorable urinary arsenic profile have an increased UC risk even at low exposure levels.

  16. Rice consumption and urinary concentrations of arsenic in US adults.

    PubMed

    Wei, Yudan; Zhu, Jianmin; Nguyen, An

    2014-01-01

    Exposure to inorganic arsenic in the general population occurs mainly from drinking water and food sources. This study examined the association between rice consumption and urinary concentrations of arsenic in US adults, aged 20-85 years, in the 2003-2006 National Health and Nutrition Examination Survey. Significantly higher geometric means of creatinine-corrected urinary concentrations of total arsenic (TAs) and dimethylarsinic acid (DMA) were found in participants who consumed rice more than twice per week, compared to the reference group. Multivariate logistic regression analysis revealed a statistically significant association between rice consumption and urinary concentrations of TAs [odds ratio (OR) = 1.51 (1.08, 2.09)] and DMA [OR = 2.24 (1.57, 3.21)] after adjustment for demographic variables, seafood intake (the main source of organic arsenic), and source of drinking water. Furthermore, significant variations in rice consumption and urinary concentrations of arsenic were observed in different racial groups. This study demonstrated that rice consumption contributed to inorganic arsenic exposure in US adults.

  17. Influence of MRP1 G1666A and GSTP1 Ile105Val genetic variants on the urinary and blood arsenic levels of Turkish smelter workers.

    PubMed

    Kaya-Akyüzlü, Dilek; Kayaaltı, Zeliha; Söylemezoğlu, Tülin

    2016-04-01

    To understand the cellular mechanisms responsible for arsenic metabolism and transport pathways plays a fundamental role in order to prevent the arsenic-induced toxicity. The effect of MRP1 G1666A and GSTP1 Ile105Val polymorphisms on blood and urinary arsenic levels were determined in 95 Turkish smelter workers. Blood and urinary arsenic concentrations were measured by GF-AAS with Zeeman correction and gene polymorphisms were investigated by PCR-RFLP method. The mean blood and urinary arsenic levels were 21.60±12.28μg/L and 5.58±4.37μg/L, respectively. A significant association between MRP1 1666A allele and urinary arsenic levels was found (p=0.001). GSTP1 Ile105Val polymorphism was detected not to be associated with either blood or urinary arsenic levels (p=0.384, p=0.440, respectively). Significant association was also detected between MRP1A(-)/GSTP1Val(-) genotypes and urinary arsenic levels (p=0.001). This study suggested that MRP1 G1666A alone and, also, combined with GSTP1 Ile105Val were associated with inter-individual variations in urinary arsenic levels, but not with blood arsenic levels.

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

    SciTech Connect

    Huang, Chao-Yuan; Su, Chien-Tien; Chung, Chi-Jung; Pu, Yeong-Shiau; Chu, Jan-Show; Yang, Hsiu-Yuan; Wu, Chia-Chang; Hsueh, Yu-Mei

    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 with 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.

  19. 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.

  20. Comparative genomic hybridization study of arsenic-exposed and non-arsenic-exposed urinary transitional cell carcinoma

    SciTech Connect

    Hsu, L.-I; Chiu, Allen W.; Pu, Y.-S.; Wang, Y.-H.; Huan, Steven K.; Hsiao, C.-H.; Hsieh, F.-I; Chen, C.-J.

    2008-03-01

    To compare the differences in DNA aberrations between arsenic-exposed and non-arsenic-exposed transitional cell carcinoma (TCC), we analyzed 19 arsenic-exposed and 29 non-arsenic-exposed urinary TCCs from Chi-Mei Hospital using comparative genomic hybridization. DNA aberrations were detected in 42 TCCs including 19 arsenic-exposed and 23 non-arsenic-exposed TCCs. Arsenic-exposed TCCs had more changes than unexposed TCCs (mean {+-} SD, 6.6 {+-} 2.9 vs. 2.9 {+-} 2.2). Arsenic exposure was significantly associated with the number of DNA aberrations after adjustment for tumor stage, tumor grade and cigarette smoking in multiple regression analysis. The most frequent DNA gains, which were strikingly different between arsenic-exposed and non-arsenic-exposed TCCs, included those at 1p, 4p, 4q and 8q. A much higher frequency of DNA losses in arsenic-exposed TCCs compared with non-arsenic-exposed TCCs was observed in 10q, 11p and 17p. Chromosomal loss in 17p13 was associated not only with arsenic exposure, but also with tumor stage and grade. The p53 immunohistochemistry staining showed that chromosome 17p13 loss was associated with either p53 no expression (25%) or p53 overexpression (75%). The findings suggest that long-term arsenic exposure may increase the chromosome abnormality in TCC, and 17p loss plays an important role in arsenic-induced urinary carcinogenesis.

  1. Urinary arsenic speciation and its correlation with 8-OHdG in Chinese residents exposed to arsenic through coal burning

    SciTech Connect

    Li, X.; Pi, J.B.; Li, B.; Xu, Y.Y.; Jin, Y.P.; Sun, G.F.

    2008-10-15

    In contrast to arsenicosis caused by consumption of water contaminated by naturally occurring inorganic arsenic, human exposure to this metalloid through coal burning has been rarely reported. In this study, arsenic speciation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in urine were determined in the Chinese residents exposed to arsenic through coal burning in Guizhou, China, an epidemic area of chronic arsenic poisoning caused by coal burning. The urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic (tAs) of high-arsenic exposed subjects were significantly higher than those of low-arsenic exposed residents. A biomarker of oxidative DNA damage, urinary 8-OHdG level was significantly higher in high-arsenic exposed subjects than that of low exposed. Significant positive correlations were found between 8-OHdG levels and concentrations of iAs, MMA, DMA and tAs, respectively. In addition, a significant negative correlation was observed between 8-OHdG levels and the secondary methylation ratio (DMA/(MMA + DMA)). The results suggest that chronic arsenic exposure through burning coal rich in arsenic is associated with oxidative DNA damages, and that secondary methylation capacity is potentially related to the susceptibility of individuals to oxidative DNA damage induced by arsenic exposure through coal burning in domestic living.

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

    PubMed

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

    1997-08-01

    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.

  3. 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.

  4. Developmental and genetic modulation of arsenic biotransformation: A gene by environment interaction?

    SciTech Connect

    Meza, Mercedes; Gandolfi, A. Jay; Klimecki, Walter T.

    2007-08-01

    The complexity of arsenic toxicology has confounded the identification of specific pathways of disease causation. One focal point of arsenic research is aimed at fully characterizing arsenic biotransformation in humans, a process that appears to be quite variable, producing a mixture of several arsenic species with greatly differing toxic potencies. In an effort to characterize genetic determinants of variability in arsenic biotransformation, a genetic association study of 135 subjects in western Sonora, Mexico was performed by testing 23 polymorphic sites in three arsenic biotransformation candidate genes. One gene, arsenic 3 methyltransferase (AS3MT), was strongly associated with the ratio of urinary dimethylarsinic acid to monomethylarsonic acid (D/M) in children (7-11 years) but not in adults (18-79 years). Subsequent analyses revealed that the high D/M values associated with variant AS3MT alleles were primarily due to lower levels of monomethylarsonic acid as percent of total urinary arsenic (%MMA5). In light of several reports of arsenic-induced disease being associated with relatively high %MMA5 levels, these findings raise the possibility that variant AS3MT individuals may suffer less risk from arsenic exposure than non-variant individuals. These analyses also provide evidence that, in this population, regardless of AS3MT variant status, children tend to have lower %MMA5 values than adults, suggesting that the global developmental regulation of arsenic biotransformation may interact with genetic variants in metabolic genes to result in novel genetic effects such as those in this report.

  5. 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

    2017-03-08

    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.

  6. Metabolites of arsenic and increased DNA damage of p53 gene in arsenic plant workers

    SciTech Connect

    Wen Weihua; Wen Jinghua; Lu Lin; Liu Hua; Yang Jun; Cheng Huirong; Che Wangjun; Li Liang; Zhang Guanbei

    2011-07-01

    Recent studies have shown that monomethylarsonous acid is more cytotoxic and genotoxic than arsenate and arsenite, which may attribute to the increased levels of reactive oxygen species. In this study, we used hydride generation-atomic absorption spectrometry to determine three arsenic species in urine of workers who had been working in arsenic plants,and calculated primary and secondary methylation indexes. The damages of exon 5, 6, 8 of p53 gene were determined by the method developed by Sikorsky, et al. Results show that the concentrations of each urinary arsenic species,and damage indexes of exon 5 and 8 of p53 gene in the exposed population were significantly higher, but SMI was significantly lower than in the control group. The closely positive correlation between the damage index of exon 5 and PMI,MMA, DMA were found, but there was closely negative correlation between the damage index of exon 5 and SMI. Those findings suggested that DNA damage of exon 5 and 8 of p53 gene existed in the population occupationally exposed to arsenic. For exon 5, the important factors may include the model of arsenic metabolic transformation, the concentrations of MMA and DMA, and the MMA may be of great importance. - Research Highlights: > In our study, the mean SMI for workers came from arsenic plants is 4.06, so they may be in danger. > There are more MMA, there are more damage of exon 5 of p53 gene. > MMA and damage of exon 5 of p53 gene may be useful biomarkers to assess adverse health effects caused by arsenic.

  7. 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.

  8. 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

  9. 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.

  10. 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...

  11. Urinary Trivalent Methylated Arsenic Species in a Population Chronically Exposed to Inorganic Arsenic

    PubMed Central

    Valenzuela, Olga L.; Borja-Aburto, Victor H.; Garcia-Vargas, Gonzalo G.; Cruz-Gonzalez, Martha B.; Garcia-Montalvo, Eliud A.; Calderon-Aranda, Emma S.; Del Razo, Luz M.

    2005-01-01

    Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous 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. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs–exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis. PMID:15743710

  12. Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic.

    PubMed

    Valenzuela, Olga L; Borja-Aburto, Victor H; Garcia-Vargas, Gonzalo G; Cruz-Gonzalez, Martha B; Garcia-Montalvo, Eliud A; Calderon-Aranda, Emma S; Del Razo, Luz M

    2005-03-01

    Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous 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. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis.

  13. Urinary 8-hydroxydeoxyguanosine and urothelial carcinoma risk in low arsenic exposure area

    SciTech Connect

    Chung, C.-J.; Huang, C.-J.; Pu, Y.-S.; Su, C.-T.; Huang, Y.-K.; Chen, Y.-T.; Hsueh, Y.-M.

    2008-01-01

    Arsenic is a well-documented human carcinogen and is known to cause oxidative stress in cultured cells and animals. A hospital-based case-control study was conducted to evaluate the relationship among the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), the arsenic profile, and urothelial carcinoma (UC). Urinary 8-OHdG was measured by using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. The urinary species of inorganic arsenic and their metabolites were analyzed by high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). This study showed that the mean urinary concentration of total arsenics was significantly higher, at 37.67 {+-} 2.98 {mu}g/g creatinine, for UC patients than for healthy controls of 21.10 {+-} 0.79 {mu}g/g creatinine (p < 0.01). Urinary 8-OHdG levels correlated with urinary total arsenic concentrations (r = 0.19, p < 0.01). There were significantly higher 8-OHdG levels, of 7.48 {+-} 0.97 ng/mg creatinine in UC patients, compared to healthy controls of 5.95 {+-} 0.21 ng/mg creatinine. Furthermore, female UC patients had higher 8-OHdG levels of 9.22 {+-} 0.75 than those of males at 5.76 {+-} 0.25 ng/mg creatinine (p < 0.01). Multiple linear regression analyses revealed that high urinary 8-OHdG levels were associated with increased total arsenic concentrations, inorganic arsenite, monomethylarsonic acid (MMA), and dimethylarsenate (DMA) as well as the primary methylation index (PMI) even after adjusting for age, gender, and UC status. The results suggest that oxidative DNA damage was associated with arsenic exposure, even at low urinary level of arsenic.

  14. Environmental Arsenic Exposure and Urinary 8-OHdG in Arizona and Sonora.

    PubMed

    Burgess, Jefferey L; Meza, María M; Josyula, Arun B; Poplin, Gerald S; Kopplin, Michael J; McClellen, Hannah E; Stürup, Stefan; Lantz, R Clark

    2007-01-01

    Although at high levels arsenic exposure is associated with increased cancer incidence, information on the health effects of lower exposure levels is limited. The objective of this study was to determine whether arsenic at concentrations below 40 microg/L in drinking water is associated with increased urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage and repair. Urine samples were collected from 73 nonsmoking adults residing in two communities in Arizona (mean tap water arsenic (microg/L) 4.0 +/- 2.3 and 20.3 +/- 3.7), and 51 subjects in four communities in Sonora, Mexico (mean tap water arsenic (microg/L) ranging from 4.8 +/- 0.1 to 33.3 +/- 0.6). Although urinary arsenic concentration increased with higher exposure in tap water, urinary 8-OHdG concentration did not differ by community within Arizona or Sonora, and was not associated with urinary arsenic concentration. At the exposure levels evaluated in this study, drinking water arsenic was not associated with increased DNA oxidation as measured by urinary 8-OHdG.

  15. Biological and behavioral modifiers of urinary arsenic metabolic profiles in a U.S. population

    EPA Science Inventory

    Biological and behavioral modifiers of urinary arsenic metabolic profiles in a U.S. population David J. Thomas – ISTD, NHEERL Edward F. Hudgens – EHPD, NHEERL John Rogers - Westat Relations between intensity of arsenic exposure from home tap water and levels of inorganic As ...

  16. Urinary arsenic speciation profile in ethnic group of the Atacama desert (Chile) exposed to variable arsenic levels in drinking water.

    PubMed

    Yáñez, Jorge; Mansilla, Héctor D; Santander, I Paola; Fierro, Vladimir; Cornejo, Lorena; Barnes, Ramón M; Amarasiriwardena, Dulasiri

    2015-01-01

    Ethnic groups from the Atacama Desert (known as Atacameños) have been exposed to natural arsenic pollution for over 5000 years. This work presents an integral study that characterizes arsenic species in water used for human consumption. It also describes the metabolism and arsenic elimination through urine in a chronically exposed population in northern Chile. In this region, water contained total arsenic concentrations up to 1250 μg L(-1), which was almost exclusively As(V). It is also important that this water was ingested directly from natural water sources without any treatment. The ingested arsenic was extensively methylated. In urine 93% of the arsenic was found as methylated arsenic species, such as monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)]. The original ingested inorganic species [As(V)], represent less than 1% of the total urinary arsenic. Methylation activity among individuals can be assessed by measuring primary [inorganic As/methylated As] and secondary methylation [MMA/DMA] indexes. Both methylation indexes were 0.06, indicating a high biological converting capability of As(V) into MMA and then MMA into DMA, compared with the control population and other arsenic exposed populations previously reported.

  17. Use of human metabolic studies and urinary arsenic speciation is assessing arsenic exposure

    SciTech Connect

    Johnson, L.R.; Farmer, J.G. Univ. of Edinburgh )

    1991-01-01

    The use of hair and nail analyses to assess human exposure to the trace metalloid arsenic (As) is hindered by the possibility of external contamination. Even though urine represents the major excretory route, its use as an indicator of exposure is limited when no distinction is made between the nontoxic organoarsenical (arsenobetaine) excreted following the consumption of seafood and the toxic inorganic forms of As and related metabolites. The development of analytical techniques capable of separating the different chemical species of As in urine have shown that the ingestion of inorganic As (AsV or AsIII) by animals and man triggers an in vivo reduction/methylation process resulting in excretion of the less toxic species, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA). This paper establishes the uptake, bio-transformation and elimination patterns reflected in urinary As following carefully controlled experimental exposure.

  18. Urinary arsenic metabolism in a Western Chinese population exposed to high-dose inorganic arsenic in drinking water: Influence of ethnicity and genetic polymorphisms

    SciTech Connect

    Fu, Songbo; Wu, Jie; Li, Yuanyuan; Liu, Yan; Gao, Yanhui; Yao, Feifei; Qiu, Chuanying; Song, Li; Wu, Yu; Liao, Yongjian; Sun, Dianjun

    2014-01-01

    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, while 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.

  19. Measured versus modeled dietary arsenic and relation to urinary arsenic excretion and total exposure

    PubMed Central

    Kurzius-Spencer, Margaret; O’Rourke, Mary Kay; Hsu, Chiu-Hsieh; Hartz, Vern; Harris, Robin B.; Burgess, Jefferey L.

    2014-01-01

    Chronic exposure to arsenic (As) in food and water is a significant public health problem. Person-specific aggregate exposure is difficult to collect, and modeling based on limited food As residue databases is of uncertain reliability. Two, cross-sectional, population exposure studies—the National Human Exposure Assessment Survey (NHEXAS)-Arizona and the Arizona Border Survey (ABS)— had a total of 252 subjects with diet, water, and urinary As data. Total As was measured in 24-hour duplicate diet samples and modeled using 24-hour diet diaries in conjunction with several published food surveys of As. Two-stage regression was used to assess the effects of dietary As on urinary total As (uAs): 1) generalized linear mixed models of uAs above versus below the limit of detection (LOD); and 2) restricted models limited to those subjects with uAs > LOD, using bootstrap sampling and mixed models adjusted for age, sex, BMI, ethnicity, current smoking, and As intake from drinking and cooking water. In restricted models, measured and modeled estimates were significant predictors of uAs. Modeled dietary As based on Total Diet Study mean residues greatly underestimated dietary intake. In households with tap water As ≤ 10 ppb, over 93% of total As exposure was attributable to diet. PMID:23321855

  20. Occurrence of trivalent monomethyl arsenic and other urinary arsenic species in a highly exposed juvenile population in Bangladesh.

    PubMed

    Kalman, David A; Dills, Russell L; Steinmaus, Craig; Yunus, Md; Khan, Al Fazal; Prodhan, Md Mofijuddin; Yuan, Yan; Smith, Allan H

    2014-01-01

    Following reports of high cytotoxicity and mutagenicity of monomethyl arsonous acid (MMA(III)) and early reports of urinary MMA(III) in arsenic-exposed individuals, MMA(III) has often been included in population studies. Use of urinary MMA(III) as an indicator of exposure and/or health risk is challenged by inconsistent results from field studies and stability studies, which indicate potential artifacts. We measured urinary arsenic species in children chronically exposed to arsenic in drinking water, using collection, storage, and analysis methods shown to conserve MMA(III). MMA(III) was easily oxidized in sample storage and processing, but recoveries of 80% or better in spiked urine samples were achieved. Attempts to preserve the distribution of MMA between trivalent and pentavalent forms using complexing agents were unsuccessful and MMA(III) spiked into treated urine samples actually showed lower stability than in untreated samples. In 643 urine samples from a highly exposed population from the Matlab district in Bangladesh stored for 3-6 months at ≤-70 °C, MMA(III) was detected in 41 samples, with an estimated median value of 0.3 μg/l, and levels of MMA(III) above 1 μg/l in only two samples. The low urinary concentrations in highly exposed individuals and known difficulties in preserving sample oxidation state indicate that urinary MMA(III) is not suitable for use as an epidemiological biomarker.

  1. 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...

  2. Association of Children’s Urinary CC16 Levels with Arsenic Concentrations in Multiple Environmental Media

    PubMed Central

    Beamer, Paloma I.; Klimecki, Walter T.; Loh, Miranda; Van Horne, Yoshira Ornelas; Sugeng, Anastasia J.; Lothrop, Nathan; Billheimer, Dean; Guerra, Stefano; Lantz, Robert Clark; Canales, Robert A.; Martinez, Fernando D.

    2016-01-01

    Arsenic exposure has been associated with decreased club cell secretory protein (CC16) levels in adults. Further, both arsenic exposure and decreased levels of CC16 in childhood have been associated with decreased adult lung function. Our objective was to determine if urinary CC16 levels in children are associated with arsenic concentrations in environmental media collected from their homes. Yard soil, house dust, and tap water were taken from 34 homes. Urine and toenail samples were collected from 68 children. All concentrations were natural log-transformed prior to data analysis. There were associations between urinary CC16 and arsenic concentration in soil (b = −0.43, p = 0.001, R2 = 0.08), water (b = −0.22, p = 0.07, R2 = 0.03), house dust (b = −0.37, p = 0.07, R2 = 0.04), and dust loading (b = −0.21, p = 0.04, R2 = 0.04). In multiple analyses, only the concentration of arsenic in soil was associated with urinary CC16 levels (b = −0.42, p = 0.02, R2 = 0.14 (full model)) after accounting for other factors. The association between urinary CC16 and soil arsenic may suggest that localized arsenic exposure in the lungs could damage the airway epithelium and predispose children for diminished lung function. Future work to assess this possible mechanism should examine potential associations between airborne arsenic exposures, CC16 levels, lung function, and other possible confounders in children in arsenic-impacted communities. PMID:27223295

  3. Association of urinary monomethylated arsenic concentration and risk of hypertension: a cross-sectional study from arsenic contaminated areas in northwestern China

    PubMed Central

    2013-01-01

    Background Although some studies mainly from Taiwan, Bangladesh and the United States, have suggested a consistent dose–response increase in the prevalence of hypertension with increasing arsenic exposure, the association between chronic environmental arsenic exposure and the risk of hypertension is still inconclusive. Most of the studies discussed the association from the point of view of arsenic concentration in drinking water or cumulative arsenic exposure (CAE), few involved arsenic speciation into the discussion. In this cross-sectional study, we evaluated the potential association between environmental arsenic exposure through drinking water and the prevalence of hypertension by analyzing not only CAE but also urinary arsenic speciation, and provided data on arsenic exposure and hypertension from mainland of China. Methods A cross-sectional study was conducted in one of the arsenic contaminated areas in the northwest of China. Among a total of 1005 residents who voluntarily participated in the study, 604 of eligible subjects were confirmed and interviewed door to door. Standing height, body weight, and blood pressure were measured. First void urine was collected and measured for the concentration of urinary arsenic speciation. CAE was calculated in a subpopulation of 360 subjects with detailed water consumption history. The association between urinary arsenic speciation, CAE and the risk of hypertension were analyzed by multiple logistic regressions. Results We found that the levels of urinary arsenic species of inorganic arsenic (iAs), monomethylated arsenic (MMA), dimethylated arsenic (DMA) and total arsenic (tAs) were significantly correlated with systolic or pulse blood pressure. A positive relationship was found between the highest tertile of CAE and hypertension in a dose-dependent manner. Subjects with higher concentration of urinary MMA or lower percentage of DMA tended to be liable to suffer from hypertension. A significant increasing trend of the

  4. Differences in urinary arsenic metabolites between diabetic and non-diabetic subjects in Bangladesh.

    PubMed

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

    2013-03-12

    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.

  5. 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.

  6. 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

  7. A Pathway-based Analysis of Urinary Arsenic Metabolites and Skin Lesions

    PubMed Central

    Kile, Molly L.; Hoffman, Elaine; Rodrigues, Ema G.; Breton, Carrie V.; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Hsueh, Yu-Mei; Christiani, David C.

    2011-01-01

    Inorganic arsenic is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Limited evidence suggests that the ability to fully metabolize arsenic into DMA influences susceptibility to disease. To determine whether percentage of MMA was predictive of disease, the authors used data from a case-control study conducted in Bangladesh (2001–2003). Persons who were diagnosed with keratosis, melanosis, Bowen's disease, or squamous cell carcinoma were matched on age, sex, and village to persons without these conditions. This analysis was restricted to persons who had no missing data on covariates (859 cases, 868 controls). A path analysis was used to evaluate simultaneously the association between the percentage of all urinary arsenic metabolites and the odds of skin lesions using PROC CALIS in SAS, version 9.1 (SAS Institute, Inc., Cary, North Carolina) and Mplus, version 6.1 (Muthén & Muthén, Los Angeles, California). The odds of skin lesions were significantly associated with log10 percentage of MMA (adjusted odds ratio (ORadj) = 1.56, 95% confidence interval (CI): 1.15, 2.12) but not log10 percentage of inorganic arsenic (ORadj = 1.06, 95% CI: 0.75, 1.50) or log10 percentage of DMA (ORadj = 1.07, 95% CI: 0.33, 3.46). This novel analysis confirmed that persons who excrete a higher proportion of MMA have a greater risk of skin lesions after data are adequately controlled for urinary arsenic metabolites, current arsenic exposure, and other risk factors. PMID:21378128

  8. Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated rats

    SciTech Connect

    Adair, Blakely M.; Moore, Tanya; Conklin, Sean D.; Creed, John T.; Wolf, Douglas C.; Thomas, David J. . E-mail: thomas.david@epa.gov

    2007-07-15

    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 dimethylated and trimethylated arsenicals; urines were analyzed for these arsenicals and their thiolated derivatives. In dimethylarsinic acid-treated rats, highest concentrations of dimethylated arsenic were found in blood. In lung, liver, and kidney, concentrations of dimethylated arsenic exceeded those of trimethylated species; in urinary bladder and urine, trimethylated arsenic predominated. Dimethylthioarsinic acid and trimethylarsine sulfide were present in urine of dimethylarsinic acid-treated rats. Concentrations of dimethylated arsenicals were similar in most tissues of dimethylarsinic acid- and arsenate-treated rats, including urinary bladder which is the target for dimethylarsinic acid-induced carcinogenesis in the rat. Mean concentration of dimethylated arsenic was significantly higher (P < 0.05) in urine of dimethylarsinic acid-treated rats than in arsenate-treated rats, suggesting a difference between treatment groups in the flux of dimethylated arsenic through urinary bladder. Concentrations of trimethylated arsenic concentrations were consistently higher in dimethylarsinic acid-treated rats than in arsenate-treated rats; these differences were significant (P < 0.05) in liver, urinary bladder, and urine. Concentrations of dimethylthioarsinic acid and trimethylarsine sulfide were higher in urine from dimethylarsinic acid-treated rats than from arsenate-treated rats. Dimethylarsinic acid is extensively metabolized in the rat, yielding significant concentrations of trimethylated species and of thiolated derivatives. One or more of these metabolites could be the species causing alterations of cellular function that lead to tumors in the urinary bladder.

  9. Oxidative DNA damage estimated by urinary 8-hydroxy-2'-deoxyguanosine and arsenic in glass production workers.

    PubMed

    Lin, Tser-Sheng; Wu, Chin-Ching; Wu, Jyun-De; Wei, Chun-Han

    2012-07-01

    A total of 130 male glass workers, including 33 administrative workers, 18 batch house workers, 42 craftsmen, and 37 melting process workers, were recruited to investigate the potential DNA damage resulting from toxic element exposure. The occupational exposure to trace elements, including arsenic (As), cadmium (Cd), manganese (Mn), nickel (Ni), lead (Pb), and selenium (Se), was estimated by their urinary levels as internal doses. In addition, all participants filled a self-filled questionnaire indicating their individual information. The average levels of urinary As, Cd, Mn, Ni, Pb, Se, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were 282.3 ± 464.6, 3.07 ± 5.39, 3.81 ± 11.43, 81.48 ± 138.9, 18.23 ± 49.61, 165.2 ± 224.9, and 17.21 ± 26.34 μg/g creatinine, respectively. The urinary levels of 8-OHdG and toxic elements were strongly associated with the work nature of the worker, with an exception of Mn and Pb. In contrast, the levels of toxic element were not influenced by age, smoking behavior, and alcohol consumption. The urinary 8-OHdG was found significantly higher in higher internal exposure groups of As, Cd, Ni, and Se. However, the stepwise multiple regression models showed that urinary 8-OHdG was only associated with urinary As and heat stress but inversely with age.

  10. Altered Gene Expression by Low-Dose Arsenic Exposure in Humans and Cultured Cardiomyocytes: Assessment by Real-Time PCR Arrays

    PubMed Central

    Mo, Jinyao; Xia, Yajuan; Wade, Timothy J.; DeMarini, David M.; Davidson, Mercy; Mumford, Judy

    2011-01-01

    Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA). We found that expression of tumor necrosis factor-α (TNF-α), which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-μM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes. PMID:21776218

  11. 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.

  12. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    SciTech Connect

    Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  13. Urinary arsenic metabolism in a Western Chinese population exposed to high-dose inorganic arsenic in drinking water: influence of ethnicity and genetic polymorphisms.

    PubMed

    Fu, Songbo; Wu, Jie; Li, Yuanyuan; Liu, Yan; Gao, Yanhui; Yao, Feifei; Qiu, Chuanying; Song, Li; Wu, Yu; Liao, Yongjian; Sun, Dianjun

    2014-01-01

    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 969μg/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, while 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.

  14. 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

  15. 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-...

  16. 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...

  17. 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...

  18. 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...

  19. 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 ...

  20. 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.

  1. COMPARISON OF IN VITRO AND IN VIVO RESPONSES TO ARSENIC: GENE EXPRESSION PROFILING IN NORMAL HUMAN EPIDERMAL KERATINOCYTES AND HYPERKERATOSES FROM ARSENIC-EXPOSED HUMANS

    EPA Science Inventory

    Chronic exposure to arsenic is positively associated with skin, urinary bladder, lung, liver and kidney cancer development in humans. Elucidating the mode of action of arsenic carcinogenesis is a complicated issue as target cells are exposed to different toxic species of arsenic....

  2. Distribution of blood lead, blood cadmium, urinary cadmium, and urinary arsenic levels in employees of a copper smelter

    SciTech Connect

    Lilis, R.; Valciukas, J.A.; Weber, J.P.; Fischbein, A.; Nicholson, W.J.; Campbell, C.; Malkin, J.; Selikoff, I.J.

    1984-02-01

    A cross-sectional medical examination of a copper smelter work force included determination of blood lead (Pb-B), zinc protoporphyrin (ZPP), blood cadmium (Cd-B), urinary cadmium (Cd-U), and urinary arsenic (As-U), since it was known that such metal impurities were present in the copper concentrate. A total of 776 copper smelter employees (680 active and 96 retirees and ex-employees) were examined. Another 144 men, never employed in the smelter, but who had worked in copper mines (and sometimes in gold mines) were also examined. Mean Pb-B, ZPP, Cd-B, and As-U were significantly higher in active copper smelter employees than in retirees or miners, indicating exposure and absorption in the copper smelter. Significant correlations between Pb-B and Cd-B, and Cd-U and As-U were present, confirming the common source of absorption. Although there was evidence for an increased lead absorption, this was very moderate, with practically no Pb-B levels in excess of 60 ..mu..g/dl. A marked effect of smoking on blood cadmium levels was present; nevertheless, for all smoking categories Cd-B levels were significantly higher in active employees, indicating the independent contribution of exposure to cadmium in the smelter. Cd-U did not exceed 10 ..mu..g/g creatinine, the generally accepted critical level for the kidney, but was higher than 2 ..mu..g/g cretinine, a level very rarely exceeded in the general population, in a sizable proportion of those examined. The highest Cd-U levels were found in retired copper smelter employees; age might have been a contributing factor, besides a longer duration of exposure in the smelter.

  3. Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen

    SciTech Connect

    Waalkes, Michael P. . E-mail: waalkes@niehs.nih.gov; Liu Jie; Ward, Jerrold M.; Diwan, Bhalchandra A.

    2006-09-15

    Pregnant CD1 mice received 85 ppm arsenite in the drinking water from gestation day 8 to 18, groups (n = 35) of male offspring were subsequently injected on postpartum days 1 through 5 with diethylstilbestrol (DES; 2 {mu}g/pup/day) or tamoxifen (TAM; 10 {mu}g/pup/day), and tumor formation was assessed over 90 weeks. Arsenic alone increased hepatocellular carcinoma (14%), adenoma (23%) and total tumors (31%) compared to control (0, 2 and 2%, respectively). Arsenic alone also increased lung adenocarcinoma, adrenal cortical adenoma and renal cystic tubular hyperplasia compared to control. Compared to arsenic alone, arsenic plus DES increased liver tumor incidence in mice at risk 2.2-fold and increased liver tumor multiplicity (tumors/liver) 1.8-fold. The treatments alone did not impact urinary bladder carcinogenesis, but arsenic plus TAM significantly increased formation of urinary bladder transitional cell tumors (papilloma and carcinoma; 13%) compared to control (0%). Urinary bladder proliferative lesions (combined tumors and hyperplasia) were also increased by arsenic plus TAM (40%) or arsenic plus DES (43%) compared to control (0%) or the treatments alone. Urinary bladder proliferative lesions occurred in the absence of any evidence of uroepithelial cytotoxic lesions. Urinary bladder lesions and hepatocellular carcinoma induced by arsenic plus TAM and/or DES overexpressed estrogen receptor-{alpha}, indicating that aberrant estrogen signaling may have been a factor in the enhanced carcinogenic response. Thus, in male CD1 mice, gestational arsenic exposure alone induced liver adenoma and carcinoma, lung adenocarcinoma, adrenal adenoma and renal cystic hyperplasia. Furthermore, DES enhanced transplacental arsenic-induced hepatocarcinogenesis. In utero arsenic also initiated urinary bladder tumor formation when followed by postnatal TAM and uroepithelial proliferative lesions when followed by TAM or DES.

  4. Arsenic

    MedlinePlus

    ... and minerals. Arsenic compounds are used to preserve wood, as pesticides, and in some industries. Arsenic can ... Breathing sawdust or burning smoke from arsenic-treated wood Living in an area with high levels of ...

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

    SciTech Connect

    Wu, M.-M.; Chiou, H.-Y. . E-mail: hychiou@tmu.edu.tw; Hsueh, Y.-M.; Hong, C.-T.; Su, C.-L.; Chang, S.-F.; Huang, W.-L.; Wang, H.-T.; Wang, Y.-H.; Hsieh, Y.-C.; Chen, C.-J.

    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 by 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.

  6. Evaluation of gene expression changes in human primary lung epithelial cells following 24-hr exposures to inorganic arsenic and its methylated metabolites and to arsenic trioxide.

    PubMed

    Efremenko, Alina Y; Seagrave, JeanClare; Clewell, Harvey J; Van Landingham, Cynthia; Gentry, P Robinan; Yager, Janice W

    2015-06-01

    The concentration response for altered gene expression in primary lung epithelial cells was determined following two treatments with arsenicals: (1) a mixture of trivalent arsenic compounds representative of urinary arsenic concentrations in exposed human populations, and (2) arsenite (As2 O3 ) a common form of inhaled arsenic dust that is frequently used in both in vivo and in vitro experimental exposures. Biochemical assays did not detect any evidence of cytotoxicity at the concentrations used, apart from a concentration-related increase in cellular heme oxygenase that was also indicated by the genomic analysis. Cell signal pathway enrichment analysis indicated similar responses to both treatments, with concentration-related responses in pathways related to cell adhesion, cytoskeleton remodeling, development (morphogenesis), cell cycle control, and to a lesser extent inflammatory responses. These cellular responses to arsenic were consistent with those observed in a previous study with primary uroepithelial cells. Benchmark dose analysis also demonstrated similar potency of the two treatments as well as comparable sensitivity of the two cell types. A number of genes showing similar concentration-dependent expression across individuals in both bladder and lung cells were identified, including heme oxygenase 1, thioredoxin reductase, DNA damage binding protein 2, and thrombomodulin. The data on human primary lung cells from this study, together with the data from human primary uroepithelial cells, support a conclusion that biological responses to arsenic by human cells under study conditions are unlikely to occur at concentrations below 0.1 µM. Environ. Mol. Mutagen. 56:477-490, 2015. © 2015 Wiley Periodicals, Inc.

  7. 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...

  8. Urinary Metabolomics Revealed Arsenic Internal Dose-Related Metabolic Alterations: A Proof-of-Concept Study in a Chinese Male Cohort

    PubMed Central

    2015-01-01

    Urinary biomonitoring provides the most accurate arsenic exposure assessment; however, to improve the risk assessment, arsenic-related metabolic biomarkers are required to understand the internal processes that may be perturbed, which may, in turn, link the exposure to a specific health outcome. This study aimed to investigate arsenic-related urinary metabolome changes and identify dose-dependent metabolic biomarkers as a proof-of-concept of the information that could be obtained by combining metabolomics and targeted analyses. Urinary arsenic species such as inorganic arsenic, methylarsonic acid, dimethylarsinic acid and arsenobetaine were quantified using high performance liquid chromatography (HPLC)-inductively coupled plasma-mass spectrometry in a Chinese adult male cohort. Urinary metabolomics was conducted using HPLC-quadrupole time-of-flight mass spectrometry. Arsenic-related metabolic biomarkers were investigated by comparing the samples of the first and fifth quintiles of arsenic exposure classifications using a partial least-squares discriminant model. After the adjustments for age, body mass index, smoking, and alcohol consumption, five potential biomarkers related to arsenic exposure (i.e., testosterone, guanine, hippurate, acetyl-N-formyl-5-methoxykynurenamine, and serine) were identified from 61 candidate metabolites; these biomarkers suggested that endocrine disruption and oxidative stress were associated with urinary arsenic levels. Testosterone, guanine, and hippurate showed a high or moderate ability to discriminate the first and fifth quintiles of arsenic exposure with area-under-curve (AUC) values of 0.89, 0.87, and 0.83, respectively; their combination pattern showed an AUC value of 0.91 with a sensitivity of 88% and a specificity of 80%. Arsenic dose-dependent AUC value changes were also observed. This study demonstrated that metabolomics can be used to investigate arsenic-related biomarkers of metabolic changes; the dose-dependent trends of

  9. 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...

  10. GENE EXPRESSION CHANGES IN MOUSE BLADDER TISSUE IN RESPONSE TO INORGANIC ARSENIC

    EPA Science Inventory

    Chronic human exposures to high arsenic concentrations are associated with lung, skin, and bladder cancer. Considerable controversy exists concerning arsenic mode of action and low dose extrapolation. This investigation was designed to identify dose-response changes in gene expre...

  11. Urinary arsenic profiles and the risks of cancer mortality: A population-based 20-year follow-up study in arseniasis-endemic areas in Taiwan

    SciTech Connect

    Chung, Chi-Jung; Huang, Ya-Li; Huang, Yung-Kai; Wu, Meei-Maan; Chen, Shu-Yuan; Hsueh, Yu-Mei; Chen, Chien-Jen

    2013-04-15

    Few studies investigated the association between chronic arsenic exposure and the mortality of cancers by estimating individual urinary arsenic methylation profiles. Therefore, we compared with the general population in Taiwan to calculate the standardized mortality ratio (SMR) in arseniasis-endemic area of Taiwan from 1996 to 2010 and evaluated the dose-response relationships between environmental arsenic exposure indices or urinary arsenic profiles and the mortality of cause-specific cancer. A cohort of 1563 residents was conducted and collected their urine sample and information regarding arsenic exposure from a questionnaire. All-cause death was identified using the National Death Registry of Taiwan. Urinary arsenic profiles were measured using high performance liquid chromatography–hydride generator–atomic absorption spectrometry. We used Cox proportional hazard models to evaluate the mortality risks. In results, 193 all-site cancer deaths, and 29, 71, 43 deaths respectively for liver, lung and bladder cancers were ascertained. The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. People with high urinary InAs% or low DMA% or low secondary methylation index (SMI) were the most likely to suffer bladder cancer after adjusting other risk factors. Even stopping exposure to arsenic from the artesian well water, the mortality rates of the residents were higher than general population. Finally, urinary InAs%, DMA% and SMI could be the potential biomarkers to predict the mortality risk of bladder cancer. -- Highlights: ► The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. ► People with high urinary InAs% were the most likely to suffer bladder cancer. ► People with low DMA% or low SMI were the most likely to suffer bladder cancer.

  12. The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk is modified by glutathione S-transferase M1 gene null genotype

    SciTech Connect

    Chung, Chi-Jung; Huang, Chao-Yuan; Pu, Yeong-Shiau; Shiue, Horng-Sheng; Su, Chien-Tien; Hsueh, Yu-Mei

    2013-01-15

    Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene–environment interaction in the carcinogenesis of UC. A hospital-based case–control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography–hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain risk factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene–environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene–environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination. -- Highlights: ► Subjects with GSTM1 null genotype had significantly increased UC risk. ► UC patients had poor arsenic metabolic ability compared to controls. ► GSTM1 null genotype may modify arsenic related UC risk.

  13. EFFECTS OF DIETARY FOLATE ON ARSENIC-INDUCED GENE EXPRESSION IN MICE

    EPA Science Inventory

    Effects of Dietary Folate on Arsenic-induced Gene Expression in Mice

    Arsenic, a drinking water contaminant, is a known carcinogen. Human exposure to inorganic arsenic has been linked to tumors of skin, bladder, lung, and to a lesser extent, kidney and liver. Dietary fola...

  14. Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking water

    SciTech Connect

    Kenyon, E.M. Hughes, M.F.; Adair, B.M.; Highfill, J.H.; Crecelius, E.A.; Clewell, H.J.; Yager, J.W.

    2008-11-01

    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{sup V} because its trivalent metabolites have unique toxicities and relatively greater potency compared to their pentavalent counterparts for many endpoints. In this study, dose-dependency in tissue distribution and urinary excretion for inorganic arsenic and its methylated metabolites was assessed in female C57Bl/6 mice exposed to 0, 0.5, 2, 10 or 50 ppm arsenic (as arsenate, As{sup V}) in their drinking water for 12 weeks. No adverse effects were observed and body weight gain did not differ significantly among groups. Urinary excretion of arsenite monomethylarsonous acid (MMA{sup III}), dimethylarsinous acid (DMA{sup III}), dimethylarsinic acid (DMA{sup V}), and trimethylarsine oxide (TMAO) increased linearly with dose, whereas As{sup V} and monomethylarsonic acid (MMA{sup V}) excretion was non-linear with respect to dose. Total tissue arsenic accumulation was greatest in kidney > lung > urinary bladder >>> skin > blood > liver. Monomethyl arsenic (MMA, i.e. MMA{sup III} + MMA{sup V}) was the predominant metabolite in kidney, whereas dimethylarsenic (DMA, i.e., DMA{sup III} + DMA{sup V}) was the predominant metabolite in lung. Urinary bladder tissue had roughly equivalent levels of inorganic arsenic and dimethylarsenic, as did skin. These data indicate that pharmacokinetic models for arsenic metabolism and disposition need to include mechanisms for organ-specific accumulation of some arsenicals and that urinary metabolite profiles are not necessarily reflective of target tissue dosimetry.

  15. 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

    SciTech Connect

    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. - 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.

  16. Arsenic

    MedlinePlus

    ... basis for regulation and standard setting worldwide. The current recommended limit of arsenic in drinking-water is 10 μg/litre, although this guideline value is designated as provisional because of measurement difficulties and the practical difficulties in removing arsenic ...

  17. Distribution of Microbial Arsenic Reduction, Oxidation and Extrusion Genes along a Wide Range of Environmental Arsenic Concentrations

    PubMed Central

    Escudero, Lorena V.; Casamayor, Emilio O.; Chong, Guillermo; Pedrós-Alió, Carles; Demergasso, Cecilia

    2013-01-01

    The presence of the arsenic oxidation, reduction, and extrusion genes arsC, arrA, aioA, and acr3 was explored in a range of natural environments in northern Chile, with arsenic concentrations spanning six orders of magnitude. A combination of primers from the literature and newly designed primers were used to explore the presence of the arsC gene, coding for the reduction of As (V) to As (III) in one of the most common detoxification mechanisms. Enterobacterial related arsC genes appeared only in the environments with the lowest As concentration, while Firmicutes-like genes were present throughout the range of As concentrations. The arrA gene, involved in anaerobic respiration using As (V) as electron acceptor, was found in all the systems studied. The As (III) oxidation gene aioA and the As (III) transport gene acr3 were tracked with two primer sets each and they were also found to be spread through the As concentration gradient. Sediment samples had a higher number of arsenic related genes than water samples. Considering the results of the bacterial community composition available for these samples, the higher microbial phylogenetic diversity of microbes inhabiting the sediments may explain the increased number of genetic resources found to cope with arsenic. Overall, the environmental distribution of arsenic related genes suggests that the occurrence of different ArsC families provides different degrees of protection against arsenic as previously described in laboratory strains, and that the glutaredoxin (Grx)-linked arsenate reductases related to Enterobacteria do not confer enough arsenic resistance to live above certain levels of As concentrations. PMID:24205341

  18. Distribution of microbial arsenic reduction, oxidation and extrusion genes along a wide range of environmental arsenic concentrations.

    PubMed

    Escudero, Lorena V; Casamayor, Emilio O; Chong, Guillermo; Pedrós-Alió, Carles; Demergasso, Cecilia

    2013-01-01

    The presence of the arsenic oxidation, reduction, and extrusion genes arsC, arrA, aioA, and acr3 was explored in a range of natural environments in northern Chile, with arsenic concentrations spanning six orders of magnitude. A combination of primers from the literature and newly designed primers were used to explore the presence of the arsC gene, coding for the reduction of As (V) to As (III) in one of the most common detoxification mechanisms. Enterobacterial related arsC genes appeared only in the environments with the lowest As concentration, while Firmicutes-like genes were present throughout the range of As concentrations. The arrA gene, involved in anaerobic respiration using As (V) as electron acceptor, was found in all the systems studied. The As (III) oxidation gene aioA and the As (III) transport gene acr3 were tracked with two primer sets each and they were also found to be spread through the As concentration gradient. Sediment samples had a higher number of arsenic related genes than water samples. Considering the results of the bacterial community composition available for these samples, the higher microbial phylogenetic diversity of microbes inhabiting the sediments may explain the increased number of genetic resources found to cope with arsenic. Overall, the environmental distribution of arsenic related genes suggests that the occurrence of different ArsC families provides different degrees of protection against arsenic as previously described in laboratory strains, and that the glutaredoxin (Grx)-linked arsenate reductases related to Enterobacteria do not confer enough arsenic resistance to live above certain levels of As concentrations.

  19. Differential Methylation of the Arsenic (III) Methyltransferase Promoter According to Arsenic Exposure

    PubMed Central

    Gribble, Matthew O.; Tang, Wan-yee; Shang, Yan; Pollak, Jonathan; Umans, Jason G.; Francesconi, Kevin A.; Goessler, Walter; Silbergeld, Ellen K.; Guallar, Eliseo; Cole, Shelley A.; Fallin, M. Daniele; Navas-Acien, Ana

    2013-01-01

    Inorganic arsenic is methylated in the body by arsenic (III) methyltransferase. Arsenic methylation is thought to play a role in arsenic-related epigenetic phenomena including aberrant DNA and histone methylation. However, it is unclear whether the promoter of the AS3MT gene, which codes for arsenic (III) methyltransferase, is differentially methylated as a function of arsenic exposure. In this study we evaluated AS3MT promoter methylation according to exposure, assessed by urinary arsenic excretion in a stratified random sample of 48 participants from the Strong Heart Study who had urine arsenic measured at baseline and DNA available from 1989–1991 and 1998–1999. For this study, all data are from the 1989–1991 visit. We measured AS3MT promoter methylation at its 48 CpG loci by bisulphite sequencing. We compared mean % methylation at each CpG locus by arsenic exposure group using linear regression adjusted for study centre, age and sex. A hypomethylated region in the AS3MT promoter was associated with higher arsenic exposure. In vitro, arsenic induced AS3MT promoter hypomethylation and it increased AS3MT expression in human peripheral blood mononuclear cells. These findings may suggest that arsenic exposure influences the epigenetic regulation of a major arsenic metabolism gene. PMID:24154821

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

    SciTech Connect

    Wu, Chia-Chang; Huang, Yung-Kai; Chung, Chi-Jung; Huang, Chao-Yuan; Pu, Yeong-Shiau; Shiue, Horng-Sheng; Lai, Li-An; Lin, Ying-Chin; Su, Chien-Tien; Hsueh, Yu-Mei

    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 liquid 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.

  1. Polymorphisms in Endothelin System Genes, Arsenic Levels and Obesity Risk

    PubMed Central

    Martínez-Barquero, Vanesa; de Marco, Griselda; Martínez-Hervas, Sergio; Rentero, Pilar; Galan-Chilet, Inmaculada; Blesa, Sebastian; Morchon, David; Morcillo, Sonsoles; Rojo, Gemma; Ascaso, Juan Francisco; Real, José Tomás; Martín-Escudero, Juan Carlos; Chaves, Felipe Javier

    2015-01-01

    Background/Objectives Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity. Subjects/Methods We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex. Results We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53) Conclusions Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to

  2. 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.

  3. Urinary arsenic and porphyrin profile in C57BL/6J mice chronically exposed to monomethylarsonous acid (MMA{sup III}) for two years

    SciTech Connect

    Krishnamohan, Manonmanii; Qi, Lixia; Lam, Paul K.S.; Moore, Michael R.; Ng, Jack C.

    2007-10-01

    Arsenicals are proven carcinogens in humans and it imposes significant health impacts on both humans and animals. Recently monomethylarsonous acid (MMA{sup III}), the toxic metabolite of arsenic has been identified in human urine and believed to be more acutely toxic than arsenite and arsenate. Arsenic also affects the activity of a number of haem biosynthesis enzymes. As a part of 2-year arsenic carcinogenicity study, young female C57BL/6J mice were given drinking water containing 0, 100, 250 and 500 {mu}g/L arsenic as MMA{sup III}ad libitum. 24 h urine samples were collected at 0, 1, 2, 4, 8 weeks and every 8 weeks for up to 104 weeks. Urinary arsenic speciation and porphyrins were measured using HPLC-ICP-MS and HPLC with fluorescence detection respectively. DMA{sup V} was a major urinary metabolite detected. Significant dose-response relationship was observed between control and treatment groups after 1, 4, 24, 32, 48, 56, 88, 96 and 104 weeks. The level of uroporphyrin in 250 and 500 {mu}g As/L group is significantly different from the control group after 4, 8, 16, 32, 56, 72, 80, 96 and 104 weeks. Coproporphyrin I level in 500 {mu}As/L group is significantly different from control group after 8, 24, 32, 40, 56, 72, 80, 88 and 104 weeks. After 4 weeks the level of coproporphyrin III concentration significantly increased in all the treatment groups compared to the control except week 16 and 48. Our results show urinary DMA{sup V} and porphyrin profile can be used as an early warning biomarker for chronic MMA{sup III} exposure before the onset of cancer.

  4. 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.

  5. Effects of arsenic exposure on DNA methylation and epigenetic gene regulation.

    PubMed

    Reichard, John F; Puga, Alvaro

    2010-02-01

    Arsenic is a nonmutagenic human carcinogen that induces tumors through unknown mechanisms. A growing body of evidence suggests that its carcinogenicity results from epigenetic changes, particularly in DNA methylation. Changes in gene methylation status, mediated by arsenic, have been proposed to activate oncogene expression or silence tumor suppressor genes, leading to long-term changes in the activity of genes controlling cell transformation. Mostly descriptive, and often contradictory, studies have demonstrated that arsenic exposure is associated with both hypo- and hyper-methylation at various genetic loci in vivo or in vitro. This ambiguity has made it difficult to assess whether the changes induced by arsenic are causally involved in the transformation process or are simply a reflection of the altered physiology of rapidly dividing cancer cells. Here, we discuss the evidence supporting changes in DNA methylation as a cause of arsenic carcinogenesis and highlight the strengths and limitations of these studies, as well as areas where consistencies and inconsistencies exist.

  6. Arsenic resistance and prevalence of arsenic resistance genes in Campylobacter jejuni and Campylobacter coli isolated from retail meats.

    PubMed

    Noormohamed, Aneesa; Fakhr, Mohamed K

    2013-08-07

    Studies that investigate arsenic resistance in the foodborne bacterium Campylobacter are limited. A total of 552 Campylobacter isolates (281 Campylobacter jejuni and 271 Campylobacter coli) isolated from retail meat samples were subjected to arsenic resistance profiling using the following arsenic compounds: arsanilic acid (4-2,048 μg/mL), roxarsone (4-2048 μg/mL), arsenate (16-8,192 μg/mL) and arsenite (4-2,048 μg/mL). A total of 223 of these isolates (114 Campylobacter jejuni and 109 Campylobacter coli) were further analyzed for the presence of five arsenic resistance genes (arsP, arsR, arsC, acr3, and arsB) by PCR. Most of the 552 Campylobacter isolates were able to survive at higher concentrations of arsanilic acid (512-2,048 μg/mL), roxarsone (512-2,048 μg/mL), and arsenate (128-1,024 μg/mL), but at lower concentrations for arsenite (4-16 μg/mL). Ninety seven percent of the isolates tested by PCR showed the presence of arsP and arsR genes. While 95% of the Campylobacter coli isolates contained a larger arsenic resistance operon that has all of the four genes (arsP, arsR, arsC and acr3), 85% of the Campylobacter jejuni isolates carried the short operon (arsP, and arsR). The presence of arsC and acr3 did not significantly increase arsenic resistance with the exception of conferring resistance to higher concentrations of arsenate to some Campylobacter isolates. arsB was prevalent in 98% of the tested Campylobacter jejuni isolates, regardless of the presence or absence of arsC and acr3, but was completely absent in Campylobacter coli. To our knowledge, this is the first study to determine arsenic resistance and the prevalence of arsenic resistance genes in such a large number of Campylobacter isolates.

  7. Influence of GSTT1 Genetic Polymorphisms on Arsenic Metabolism

    PubMed Central

    Kile, Molly L.; Houseman, E. Andres; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Hsueh, Yu-Mei; Christiani, David C.

    2014-01-01

    SUMMARY A repeated measures study was conducted in Pabna, Bangladesh to investigate factors that influence biomarkers of arsenic exposure. Drinking water arsenic concentrations were measured by inductively-coupled plasma mass spectrometry (ICP-MS) and urinary arsenic species [arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] were detected using High Performance Liquid Chromatography (HPLC) and Hydride Generated Atomic Absorption Spectrometry (HGAAS). Linear mixed effects models with random intercepts were used to evaluate the effects of arsenic contaminated drinking water, genetic polymorphisms in glutathione-S-transferase (GSTT1 and GSTM1) on total urinary arsenic, primary methylation index [MMA/(As3+As5)], secondary methylation index (DMA/MMA), and total methylation index [(MMA+DMA)/(As3+As5)]. Drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and total methylation index. A significant gene-environment interaction was observed between urinary arsenic exposure in drinking water GSTT1 but not GSTM1 where GSTT1 null individuals had a slightly higher excretion rate of arsenic compared to GSTT1 wildtypes after adjusting for other factors. Additionally, individuals with GSTT1 null genotypes had a higher primary methylation index and lower secondary methylation index compared to GSTT1 wildtype after adjusting for other factors. This data suggests that GSTT1 contributes to the observed variability in arsenic metabolism. Since individuals with a higher primary methylation index and lower secondary methylation index are more susceptible to arsenic related disease, these results suggest that GSTT1 null individuals may be more susceptible to arsenic-related toxicity. No significant associations were observed between GSTM1 and any of the arsenic methylation indices. PMID:24511153

  8. Influence of GSTT1 Genetic Polymorphisms on Arsenic Metabolism.

    PubMed

    Kile, Molly L; Houseman, E Andres; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Hsueh, Yu-Mei; Christiani, David C

    2013-08-01

    A repeated measures study was conducted in Pabna, Bangladesh to investigate factors that influence biomarkers of arsenic exposure. Drinking water arsenic concentrations were measured by inductively-coupled plasma mass spectrometry (ICP-MS) and urinary arsenic species [arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] were detected using High Performance Liquid Chromatography (HPLC) and Hydride Generated Atomic Absorption Spectrometry (HGAAS). Linear mixed effects models with random intercepts were used to evaluate the effects of arsenic contaminated drinking water, genetic polymorphisms in glutathione-S-transferase (GSTT1 and GSTM1) on total urinary arsenic, primary methylation index [MMA/(As3+As5)], secondary methylation index (DMA/MMA), and total methylation index [(MMA+DMA)/(As3+As5)]. Drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and total methylation index. A significant gene-environment interaction was observed between urinary arsenic exposure in drinking water GSTT1 but not GSTM1 where GSTT1 null individuals had a slightly higher excretion rate of arsenic compared to GSTT1 wildtypes after adjusting for other factors. Additionally, individuals with GSTT1 null genotypes had a higher primary methylation index and lower secondary methylation index compared to GSTT1 wildtype after adjusting for other factors. This data suggests that GSTT1 contributes to the observed variability in arsenic metabolism. Since individuals with a higher primary methylation index and lower secondary methylation index are more susceptible to arsenic related disease, these results suggest that GSTT1 null individuals may be more susceptible to arsenic-related toxicity. No significant associations were observed between GSTM1 and any of the arsenic methylation indices.

  9. Arsenic Methylation in Arabidopsis thaliana Expressing an Algal Arsenite Methyltransferase Gene Increases Arsenic Phytotoxicity

    PubMed Central

    Tang, Zhong; Lv, Yanling; Chen, Fei; Zhang, Wenwen; Rosen, Barry P.; Zhao, Fang-Jie

    2016-01-01

    Arsenic (As) contamination in soil can lead to elevated transfer of As to the food chain. One potential mitigation strategy is to genetically engineer plants to enable them to transform inorganic As to methylated and volatile As species. In this study, we genetically engineered two ecotypes of Arabidopsis thaliana with the arsenite (As(III)) S-adenosylmethyltransferase (arsM) gene from the eukaryotic alga Chlamydomonas reinhardtii. The transgenic A. thaliana plants gained a strong ability to methylate As, converting most of the inorganic As into dimethylarsenate [DMA(V)] in the shoots. Small amounts of volatile As were detected from the transgenic plants. However, the transgenic plants became more sensitive to As(III) in the medium, suggesting that DMA(V) is more phytotoxic than inorganic As. The study demonstrates a negative consequence of engineered As methylation in plants and points to a need for arsM genes with a strong ability to methylate As to volatile species. PMID:26998776

  10. Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus

    SciTech Connect

    Diaz-Villasenor, Andrea Burns, Anna L.; Hiriart, Marcia; Cebrian, Mariano E.; Ostrosky-Wegman, Patricia

    2007-12-01

    Chronic exposure to high concentrations of arsenic in drinking water is associated with an increased risk for developing type 2 diabetes. The present revision focuses on the effect of arsenic on tissues that participate directly in glucose homeostasis, integrating the most important published information about the impairment of the expression of genes related to type 2 diabetes by arsenic as one of the possible mechanisms by which it leads to the disease. Many factors are involved in the manner in which arsenic contributes to the occurrence of diabetes. The reviewed studies suggest that arsenic might increase the risk for type 2 diabetes via multiple mechanisms, affecting a cluster of regulated events, which in conjunction trigger the disease. Arsenic affects insulin sensitivity in peripheral tissue by modifying the expression of genes involved in insulin resistance and shifting away cells from differentiation to the proliferation pathway. In the liver arsenic disturbs glucose production, whereas in pancreatic beta-cells arsenic decreases insulin synthesis and secretion and reduces the expression of antioxidant enzymes. The consequences of these changes in gene expression include the reduction of insulin secretion, induction of oxidative stress in the pancreas, alteration of gluconeogenesis, abnormal proliferation and differentiation pattern of muscle and adipocytes as well as peripheral insulin resistance.

  11. 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...

  12. 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

  13. Measuring Escherichia coli Gene Expression during Human Urinary Tract Infections

    PubMed Central

    Mobley, Harry L. T.

    2016-01-01

    Extraintestinal Escherichia coli (E. coli) evolved by acquisition of pathogenicity islands, phage, plasmids, and DNA segments by horizontal gene transfer. Strains are heterogeneous but virulent uropathogenic isolates more often have specific fimbriae, toxins, and iron receptors than commensal strains. One may ask whether it is the virulence factors alone that are required to establish infection. While these virulence factors clearly contribute strongly to pathogenesis, bacteria must survive by metabolizing nutrients available to them. By constructing mutants in all major metabolic pathways and co-challenging mice transurethrally with each mutant and the wild type strain, we identified which major metabolic pathways are required to infect the urinary tract. We must also ask what else is E. coli doing in vivo? To answer this question, we examined the transcriptome of E. coli CFT073 in the murine model of urinary tract infection (UTI) as well as for E. coli strains collected and analyzed directly from the urine of patients attending either a urology clinic or a university health clinic for symptoms of UTI. Using microarrays and RNA-seq, we measured in vivo gene expression for these uropathogenic E. coli strains, identifying genes upregulated during murine and human UTI. Our findings allow us to propose a new definition of bacterial virulence. PMID:26784237

  14. T-Box Genes in the Kidney and Urinary Tract.

    PubMed

    Kispert, A

    2017-01-01

    T-box (Tbx) genes encode an ancient group of transcription factors that play important roles in patterning, specification, proliferation, and differentiation programs in vertebrate organogenesis. This is testified by severe organ malformation syndromes in mice homozygous for engineered null alleles of specific T-box genes and by the large number of human inherited organ-specific diseases that have been linked to mutations in these genes. One of the organ systems that has not been associated with loss of specific T-box gene function in human disease for long is the excretory system. However, this has changed with the finding that mutations in TBX18, a member of a vertebrate-specific subgroup within the Tbx1-subfamily of T-box transcription factor genes, cause congenital anomalies of the kidney and urinary tract, predominantly hydroureter and ureteropelvic junction obstruction. Gene expression analyses, loss-of-function studies, and lineage tracing in the mouse suggest a primary role for this transcription factor in specifying the ureteric mesenchyme in the common anlage of the kidney, the ureter, and the bladder. We review the function of Tbx18 in ureterogenesis and discuss the body of evidence that Tbx18 and other members of the T-box gene family, namely, Tbx1, Tbx2, Tbx3, and Tbx20, play additional roles in development and homeostasis of other components of the excretory system in vertebrates.

  15. Co-expression of Cyanobacterial Genes for Arsenic Methylation and Demethylation in Escherichia coli Offers Insights into Arsenic Resistance

    PubMed Central

    Yan, Yu; Xue, Xi-Mei; Guo, Yu-Qing; Zhu, Yong-Guan; Ye, Jun

    2017-01-01

    Arsenite [As(III)] and methylarsenite [MAs(III)] are the most toxic inorganic and methylated arsenicals, respectively. As(III) and MAs(III) can be interconverted in the unicellular cyanobacterium Nostoc sp. PCC 7120 (Nostoc), which has both the arsM gene (NsarsM), which is responsible for arsenic methylation, and the arsI gene (NsarsI), which is responsible for MAs(III) demethylation. It is not clear how the cells prevent a futile cycle of methylation and demethylation. To investigate the relationship between arsenic methylation and demethylation, we constructed strains of Escherichia coli AW3110 (ΔarsRBC) expressing NsarsM or/and NsarsI. Expression of NsarsI conferred MAs(III) resistance through MAs(III) demethylation. Compared to NsArsI, NsArsM conferred higher resistance to As(III) and lower resistance to MAs(III) by methylating both As(III) and MAs(III). The major species found in solution was dimethylarsenate [DMAs(V)]. Co-expression of NsarsM and NsarsI conferred As(III) resistance at levels similar to that with NsarsM alone, although the main species found in solution after As(III) biotransformation was methylarsenate [MAs(V)] rather than DMAs(V). Co-expression of NsarsM and NsarsI conferred a higher level of resistance to MAs(III) than found with expression of NsarsM alone but lower than expression of only NsarsI. Cells co-expressing both genes converted MAs(III) to a mixture of As(III) and DMAs(V). In Nostoc NsarsM is constitutively expressed, while NsarsI is inducible by either As(III) or MAs(III). Thus, our results suggest that at low concentrations of arsenic, NsArsM activity predominates, while NsArsI activity predominates at high concentrations. We propose that coexistence of arsM and arsI genes in Nostoc could be advantageous for several reasons. First, it confers a broader spectrum of resistance to both As(III) and MAs(III). Second, at low concentrations of arsenic, the MAs(III) produced by NsArsM will possibly have antibiotic-like properties and

  16. Metagenomic analysis revealed highly diverse microbial arsenic metabolism genes in paddy soils with low-arsenic contents.

    PubMed

    Xiao, Ke-Qing; Li, Li-Guan; Ma, Li-Ping; Zhang, Si-Yu; Bao, Peng; Zhang, Tong; Zhu, Yong-Guan

    2016-04-01

    Microbe-mediated arsenic (As) metabolism plays a critical role in global As cycle, and As metabolism involves different types of genes encoding proteins facilitating its biotransformation and transportation processes. Here, we used metagenomic analysis based on high-throughput sequencing and constructed As metabolism protein databases to analyze As metabolism genes in five paddy soils with low-As contents. The results showed that highly diverse As metabolism genes were present in these paddy soils, with varied abundances and distribution for different types and subtypes of these genes. Arsenate reduction genes (ars) dominated in all soil samples, and significant correlation existed between the abundance of arr (arsenate respiration), aio (arsenite oxidation), and arsM (arsenite methylation) genes, indicating the co-existence and close-relation of different As resistance systems of microbes in wetland environments similar to these paddy soils after long-term evolution. Among all soil parameters, pH was an important factor controlling the distribution of As metabolism gene in five paddy soils (p = 0.018). To the best of our knowledge, this is the first study using high-throughput sequencing and metagenomics approach in characterizing As metabolism genes in the five paddy soil, showing their great potential in As biotransformation, and therefore in mitigating arsenic risk to humans.

  17. Volatilization of Arsenic from Polluted Soil by Pseudomonas putida Engineered for Expression of the arsM Arsenic(III) S-Adenosine Methyltransferase Gene

    PubMed Central

    2015-01-01

    Even though arsenic is one of the most widespread environmental carcinogens, methods of remediation are still limited. In this report we demonstrate that a strain of Pseudomonas putida KT2440 endowed with chromosomal expression of the arsM gene encoding the As(III) S-adenosylmethionine (SAM) methyltransfase from Rhodopseudomonas palustris to remove arsenic from contaminated soil. We genetically engineered the P. putida KT2440 with stable expression of an arsM-gfp fusion gene (GE P. putida), which was inserted into the bacterial chromosome. GE P. putida showed high arsenic methylation and volatilization activity. When exposed to 25 μM arsenite or arsenate overnight, most inorganic arsenic was methylated to the less toxic methylated arsenicals methylarsenate (MAs(V)), dimethylarsenate (DMAs(V)) and trimethylarsine oxide (TMAs(V)O). Of total added arsenic, the species were about 62 ± 2.2% DMAs(V), 25 ± 1.4% MAs(V) and 10 ± 1.2% TMAs(V)O. Volatilized arsenicals were trapped, and the predominant species were dimethylarsine (Me2AsH) (21 ± 1.0%) and trimethylarsine (TMAs(III)) (10 ± 1.2%). At later times, more DMAs(V) and volatile species were produced. Volatilization of Me2AsH and TMAs(III) from contaminated soil is thus possible with this genetically engineered bacterium and could be instrumental as an agent for reducing the inorganic arsenic content of soil and agricultural products. PMID:25122054

  18. Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population.

    PubMed

    Argos, Maria; Kibriya, Muhammad G; Parvez, Faruque; Jasmine, Farzana; Rakibuz-Zaman, Muhammad; Ahsan, Habibul

    2006-07-01

    Millions of individuals worldwide are chronically exposed to arsenic through their drinking water. In this study, the effect of arsenic exposure and arsenical skin lesion status on genome-wide gene expression patterns was evaluated using RNA from peripheral blood lymphocytes of individuals selected from the Health Effects of Arsenic Longitudinal Study. Affymetrix HG-U133A GeneChip (Affymetrix, Santa Clara, CA) arrays were used to measure the expression of approximately 22,000 transcripts. Our primary statistical analysis involved identifying differentially expressed genes between participants with and without arsenical skin lesions based on the significance analysis of microarrays statistic with an a priori defined 1% false discovery rate to minimize false positives. To better characterize differential expression, we also conducted Gene Ontology and pathway comparisons in addition to the gene-specific analyses. Four-hundred sixty-eight genes were differentially expressed between these two groups, from which 312 differentially expressed genes were identified by restricting the analysis to female never-smokers. We also explored possible differential gene expression by arsenic exposure levels among individuals without manifest arsenical skin lesions; however, no differentially expressed genes could be identified from this comparison. Our findings show that microarray-based gene expression analysis is a powerful method to characterize the molecular profile of arsenic exposure and arsenic-induced diseases. Genes identified from this analysis may provide insights into the underlying processes of arsenic-induced disease and represent potential targets for chemoprevention studies to reduce arsenic-induced skin cancer in this population.

  19. Exploring the diversity of arsenic resistance genes from acid mine drainage microorganisms.

    PubMed

    Morgante, Verónica; Mirete, Salvador; de Figueras, Carolina G; Postigo Cacho, Marina; González-Pastor, José E

    2015-06-01

    The microbial communities from the Tinto River, a natural acid mine drainage environment, were explored to search for novel genes involved in arsenic resistance using a functional metagenomic approach. Seven pentavalent arsenate resistance clones were selected and analysed to find the genes responsible for this phenotype. Insights about their possible mechanisms of resistance were obtained from sequence similarities and cellular arsenic concentration. A total of 19 individual open reading frames were analysed, and each one was individually cloned and assayed for its ability to confer arsenic resistance in Escherichia coli cells. A total of 13 functionally active genes involved in arsenic resistance were identified, and they could be classified into different global processes: transport, stress response, DNA damage repair, phospholipids biosynthesis, amino acid biosynthesis and RNA-modifying enzymes. Most genes (11) encode proteins not previously related to heavy metal resistance or hypothetical or unknown proteins. On the other hand, two genes were previously related to heavy metal resistance in microorganisms. In addition, the ClpB chaperone and the RNA-modifying enzymes retrieved in this work were shown to increase the cell survival under different stress conditions (heat shock, acid pH and UV radiation). Thus, these results reveal novel insights about unidentified mechanisms of arsenic resistance.

  20. Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormality

    SciTech Connect

    Liao, Y.-T.; Li, W.-F.; Chen, C.-J.; Prineas, Ronald J.; Chen, Wei J.; Zhang Zhuming; Sun, C.-W.; Wang, S.-L.

    2009-09-01

    Arsenic has been linked to increased prevalence of cancer and cardiovascular disease (CVD), but the long-term impact of arsenic exposure remains unclear. Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies. Only recently have genes encoding enzymes responsible for arsenic metabolism, such as AS3MT and GSTO, been cloned and characterized. This study was designed to evaluate the synergistic interaction of genetic factors and arsenic exposure on electrocardiogram abnormality. A total of 216 residents from three tap water implemented villages of previous arseniasis-hyperendemic regions in Taiwan were prospectively followed for an average of 8 years. For each resident, a 12-lead conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT, GSTO1, and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42 incident cases with ECG deterioration identified among 121 baseline-normal subjects, arsenic exposure was significantly correlated with incidence of ECG abnormality. In addition, polymorphisms in two paraoxonase genes were also found associated with the incidence of ECG abnormality. A haplotype R-C-S constituted by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the increased risk. Subjects exposed to high levels of As (cumulative As exposure > 14.7 ppm-year or drinking artesian well water > 21 years) and carrying the R-C-S haplotype had significantly increased risks for ECG abnormality over those with only one risk factor. Results of this study showed a long-term arsenic effect on ECG abnormality and significant gene-gene and gene-environment interactions linked to the incidence of CVD. This finding might have important implications for a novel and potentially useful

  1. Genomic evidence reveals the extreme diversity and wide distribution of the arsenic-related genes in Burkholderiales.

    PubMed

    Li, Xiangyang; Zhang, Linshuang; Wang, Gejiao

    2014-01-01

    So far, numerous genes have been found to associate with various strategies to resist and transform the toxic metalloid arsenic (here, we denote these genes as "arsenic-related genes"). However, our knowledge of the distribution, redundancies and organization of these genes in bacteria is still limited. In this study, we analyzed the 188 Burkholderiales genomes and found that 95% genomes harbored arsenic-related genes, with an average of 6.6 genes per genome. The results indicated: a) compared to a low frequency of distribution for aio (arsenite oxidase) (12 strains), arr (arsenate respiratory reductase) (1 strain) and arsM (arsenite methytransferase)-like genes (4 strains), the ars (arsenic resistance system)-like genes were identified in 174 strains including 1,051 genes; b) 2/3 ars-like genes were clustered as ars operon and displayed a high diversity of gene organizations (68 forms) which may suggest the rapid movement and evolution for ars-like genes in bacterial genomes; c) the arsenite efflux system was dominant with ACR3 form rather than ArsB in Burkholderiales; d) only a few numbers of arsM and arrAB are found indicating neither As III biomethylation nor AsV respiration is the primary mechanism in Burkholderiales members; (e) the aio-like gene is mostly flanked with ars-like genes and phosphate transport system, implying the close functional relatedness between arsenic and phosphorus metabolisms. On average, the number of arsenic-related genes per genome of strains isolated from arsenic-rich environments is more than four times higher than the strains from other environments. Compared with human, plant and animal pathogens, the environmental strains possess a larger average number of arsenic-related genes, which indicates that habitat is likely a key driver for bacterial arsenic resistance.

  2. The Comparative Toxicogenomics Database facilitates identification and understanding of chemical-gene-disease associations: arsenic as a case study

    PubMed Central

    Davis, Allan P; Murphy, Cynthia G; Rosenstein, Michael C; Wiegers, Thomas C; Mattingly, Carolyn J

    2008-01-01

    Background The etiology of many chronic diseases involves interactions between environmental factors and genes that modulate physiological processes. Understanding interactions between environmental chemicals and genes/proteins may provide insights into the mechanisms of chemical actions, disease susceptibility, toxicity, and therapeutic drug interactions. The Comparative Toxicogenomics Database (CTD; ) provides these insights by curating and integrating data describing relationships between chemicals, genes/proteins, and human diseases. To illustrate the scope and application of CTD, we present an analysis of curated data for the chemical arsenic. Arsenic represents a major global environmental health threat and is associated with many diseases. The mechanisms by which arsenic modulates these diseases are not well understood. Methods Curated interactions between arsenic compounds and genes were downloaded using export and batch query tools at CTD. The list of genes was analyzed for molecular interactions, Gene Ontology (GO) terms, KEGG pathway annotations, and inferred disease relationships. Results CTD contains curated data from the published literature describing 2,738 molecular interactions between 21 different arsenic compounds and 1,456 genes and proteins. Analysis of these genes and proteins provide insight into the biological functions and molecular networks that are affected by exposure to arsenic, including stress response, apoptosis, cell cycle, and specific protein signaling pathways. Integrating arsenic-gene data with gene-disease data yields a list of diseases that may be associated with arsenic exposure and genes that may explain this association. Conclusion CTD data integration and curation strategies yield insight into the actions of environmental chemicals and provide a basis for developing hypotheses about the molecular mechanisms underlying the etiology of environmental diseases. While many reports describe the molecular response to arsenic, CTD

  3. Genes That Mediate Arsenic and Heavy Metal Detoxification in Plants

    SciTech Connect

    Lee, David A.; Gong, Ji-Ming; Schroeder, Julian I.

    2003-03-26

    To gain insight into the mechanisms of arsenic tolerance in plants, we developed a genetic screen to isolate Arabidopsis thaliana mutants with altered tolerance to arsenic. We report here on the isolation of ars1, a novel mutant with significantly increased tolerance to arsenate. ars1 accumulates similar levels of arsenic as wild type plants, but ars1 tolerance does not appear to be phytochelatin or glutathione dependent. ars1 plants do have a higher rate of phosphate uptake than wild type plants and plants grown with an excess of phosphate show increased tolerance to arsenate. Traditional models of arsenate tolerance in plants are based on the suppression of phosphate uptake pathways and, consequently, the reduced uptake of arsenate. Our data suggest that arsenate tolerance in ars1 is due to a new mechanism mediated by increased phosphate uptake in ars1. Results exploring increased metal tolerance through engineered phytochelatin expression will also be discussed.

  4. Association of oxidative stress with arsenic methylation in chronic arsenic-exposed children and adults

    SciTech Connect

    Xu Yuanyuan; Wang Yi; Zheng Quanmei; Li Xin; Li Bing; Jin Yaping; Sun Xiance; Sun Guifan

    2008-10-01

    Though oxidative stress is recognized as an important pathogenic mechanism of arsenic, and arsenic methylation capacity is suggested to be highly involved in arsenic-related diseases, the association of arsenic methylation capacity with arsenic-induced oxidative stress remains unclear. To explore oxidative stress and its association with arsenic methylation, cross-sectional studies were conducted among 208 high and 59 low arsenic-exposed subjects. Levels of urinary arsenic species [inorganic arsenic (iAs), monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] were determined by hydride generation atomic absorption spectrometry. Proportions of urinary arsenic species, the first methylation ratio (FMR) and the secondary methylation ratio (SMR) were used as indicators for arsenic methylation capacity. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were analyzed by enzyme-linked immunosorbent assay kits. Reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity in whole blood were determined to reflect anti-oxidative status. The high arsenic-exposed children and adults were significantly increased in urinary 8-OHdG concentrations but decreased in blood GSH levels compared with the low exposed children and adults. In multiple linear regression models, blood GSH levels and urinary 8-OHdG concentrations of arsenic-exposed children and adults showed strong associations with the levels of urinary arsenic species. Arsenic-exposed subjects in the lower and the upper quartiles of proportions of urinary arsenic species, FMR or SMR were significantly different in urinary 8-OHdG, blood GSH and SOD. The associations of arsenic methylation capacity with 8-OHdG, GSH and SOD were also observed in multivariate regression analyses. These results may provide linkage between arsenic methylation capacity and oxidative stress in humans and suggest that adverse health effects induced by arsenic are related to arsenic methylation through oxidative stress.

  5. Dose-Responsive Gene Expression Changes in Juvenile and Adult Mummichogs (Fundulus heteroclitus) After Arsenic Exposure

    PubMed Central

    Gonzalez, Horacio O.; Hu, Jianjun; Gaworecki, Kristen M.; Roling, Jonathan A.; Baldwin, William S.; Gardea-Torresdey, Jorge L.; Bain, Lisa J.

    2010-01-01

    The present study investigated arsenic's effects on mummichogs (Fundulus heteroclitus), while also examining what role that gender or exposure age might play. Adult male and female mummichogs were exposed to 172ppb, 575ppb, or 1,720ppb arsenic as sodium arsenite for 10 days immediately prior to spawning. No differences were noted in the number or viability of eggs between the groups, but there was a significant increase in deformities in 1,720ppb arsenic exposure group. Total RNA from adult livers or 6-week old juveniles was used to probe custom macroarrays for changes in gene expression. In females, 3% of the genes were commonly differentially expressed in the 172 and 575ppb exposure groups compared to controls. In the males, between 1.1-3% of the differentially expressed genes were in common between the exposure groups. Several genes, including apolipoprotein and serum amyloid precursor were commonly expressed in either a dose-responsive manner or were dose-specific, but consistent across genders. These patterns of regulation were confirmed by QPCR. These findings will provide us with a better understanding of the effects of dose, gender, and exposure age on the response to arsenic. PMID:20451245

  6. 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...

  7. Elevated ERCC-1 Gene Expression in blood cells associated with exposure to arsenic from drinking water in Inner Mongolia

    EPA Science Inventory

    Background: Chronic arsenic exposure has been associated with human cancers. The objective of this study was to investigate arsenic effects on a DNA nucleotide excision repair gene, ERCC1, expression in human blood cells. Material and Methods: Water and toe nail samples were coll...

  8. Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

    PubMed Central

    Wlodarczyk, Bogdan J.; Zhu, Huiping; Finnell, Richard H.

    2014-01-01

    Background In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity vary widely and depend on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Methods Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. Results When the dams in Mthfr+/− x Mthfr+/− matings were treated with 7.2mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr+/+ x Mthfr+/−, Mthfr+/− x Mthfr+/− and Mthfr−/− x Mthfr+/−) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote x wild-type versus wild-type x nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Conclusions Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure. PMID:24384392

  9. 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

  10. Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

    SciTech Connect

    Wlodarczyk, Bogdan J. Zhu, Huiping; Finnell, Richard H.

    2014-02-15

    Background: In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity varies widely and depends on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Methods: Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. Results: When the dams in Mthfr{sup +/−} × Mthfr{sup +/−} matings were treated with 7.2 mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr{sup +/+} × Mthfr{sup +/−}, Mthfr{sup +/−} × Mthfr{sup +/−} and Mthfr{sup −/−} × {sup Mthfr+/−}) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote × wild-type versus wild-type × nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Conclusions: Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure. - Highlights: • An interaction between Mthfr genotype and arsenic embryotoxicity is presented. • Maternal Mthfr genotype

  11. Diversity and Distribution of Arsenic-Related Genes Along a Pollution Gradient in a River Affected by Acid Mine Drainage.

    PubMed

    Desoeuvre, Angélique; Casiot, Corinne; Héry, Marina

    2016-04-01

    Some microorganisms have the capacity to interact with arsenic through resistance or metabolic processes. Their activities contribute to the fate of arsenic in contaminated ecosystems. To investigate the genetic potential involved in these interactions in a zone of confluence between a pristine river and an arsenic-rich acid mine drainage, we explored the diversity of marker genes for arsenic resistance (arsB, acr3.1, acr3.2), methylation (arsM), and respiration (arrA) in waters characterized by contrasted concentrations of metallic elements (including arsenic) and pH. While arsB-carrying bacteria were representative of pristine waters, Acr3 proteins may confer to generalist bacteria the capacity to cope with an increase of contamination. arsM showed an unexpected wide distribution, suggesting biomethylation may impact arsenic fate in contaminated aquatic ecosystems. arrA gene survey suggested that only specialist microorganisms (adapted to moderately or extremely contaminated environments) have the capacity to respire arsenate. Their distribution, modulated by water chemistry, attested the specialist nature of the arsenate respirers. This is the first report of the impact of an acid mine drainage on the diversity and distribution of arsenic (As)-related genes in river waters. The fate of arsenic in this ecosystem is probably under the influence of the abundance and activity of specific microbial populations involved in different As biotransformations.

  12. 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

  13. Characterization of the ars gene cluster from extremely arsenic-resistant Microbacterium sp. strain A33.

    PubMed

    Achour-Rokbani, Asma; Cordi, Audrey; Poupin, Pascal; Bauda, Pascale; Billard, Patrick

    2010-02-01

    The arsenic resistance gene cluster of Microbacterium sp. A33 contains a novel pair of genes (arsTX) encoding a thioredoxin system that are cotranscribed with an unusual arsRC2 fusion gene, ACR3, and arsC1 in an operon divergent from arsC3. The whole ars gene cluster is required to complement an Escherichia coli ars mutant. ArsRC2 negatively regulates the expression of the pentacistronic operon. ArsC1 and ArsC3 are related to thioredoxin-dependent arsenate reductases; however, ArsC3 lacks the two distal catalytic cysteine residues of this class of enzymes.

  14. Drinking-Water Arsenic Exposure Modulates Gene Expression in Human Lymphocytes from a U.S. Population

    PubMed Central

    Andrew, Angeline S.; Jewell, David A.; Mason, Rebecca A.; Whitfield, Michael L.; Moore, Jason H.; Karagas, Margaret R.

    2008-01-01

    Background Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 μg/L in the northeastern, western, and north central regions of the United States. Objectives We investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression. Methods We conducted separate Affymetrix microarray-based genomewide analyses of expression patterns. Peripheral blood lymphocyte samples from 21 controls interviewed (1999–2002) as part of a case–control study in New Hampshire were selected based on high- versus low-level arsenic exposure levels. Results The biologic functions of the transcripts that showed statistically significant abundance differences between high- and low-arsenic exposure groups included an overrepresentation of genes involved in defense response, immune function, cell growth, apoptosis, regulation of cell cycle, T-cell receptor signaling pathway, and diabetes. Notably, the high-arsenic exposure group exhibited higher levels of several killer cell immunoglobulin-like receptors that inhibit natural killer cell activity. Conclusions These findings define biologic changes that occur with chronic arsenic exposure in humans and provide leads and potential targets for understanding and monitoring the pathogenesis of arsenic-induced diseases. PMID:18414638

  15. 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...

  16. Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans.

    PubMed

    Vivante, Asaf; Kohl, Stefan; Hwang, Daw-Yang; Dworschak, Gabriel C; Hildebrandt, Friedhelm

    2014-04-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) cover a wide range of structural malformations that result from defects in the morphogenesis of the kidney and/or urinary tract. These anomalies account for about 40-50 % of children with chronic kidney disease worldwide. Knowledge from genetically modified mouse models suggests that single gene mutations in renal developmental genes may lead to CAKUT in humans. However, until recently, only a handful of CAKUT-causing genes were reported, most of them in familial syndromic cases. Recent findings suggest that CAKUT may arise from mutations in a multitude of different single gene causes. We focus here on single-gene causes of CAKUT and their developmental origin. Currently, more than 20 monogenic CAKUT-causing genes have been identified. High-throughput sequencing techniques make it likely that additional CAKUT-causing genes will be identified in the near future.

  17. Evaluation of a GFP Report Gene Construct for Environmental Arsenic Detection

    SciTech Connect

    Roberto, F.F.; Barnes, J.M.; Bruhn, D.F.

    2002-03-28

    Detection of arsenic and other heavy metal contaminants in the environment is critical to ensuring safe drinking water and effective cleanup of historic activities that have led to widespread contamination of soil and groundwater. Biosensors have the potential to significantly reduce the costs associated with site characterization and long term environmental monitoring. By exploiting the highly selective and sensitive natural mechanisms by which bacteria and other living organisms respond to heavy metals, and fusing transcriptionally active components of these mechanisms to reporter genes, such as B-galactosidase, bacterial luciferase (lux), or green fluorescent protein (GFP) from marine jellyfish, it is possible to produce inexpensive, yet effective biosensors. This article describes the response to submicrogram quantities of arsenite and arsenate of a whole cell arsenic biosensor utilizing a GFP reporter gene.

  18. Dietary arsenic exposure with low level of arsenic in drinking water and biomarker: a study in West Bengal.

    PubMed

    Mazumder, Debendra Nath Guha; Deb, Debasree; Biswas, Anirban; Saha, Chandan; Nandy, Ashoke; Das, Arabinda; Ghose, Aloke; Bhattacharya, Kallol; Mazumdar, Kunal Kanti

    2014-01-01

    The authors investigated association of arsenic intake through water and diet and arsenic level in urine in people living in arsenic endemic region in West Bengal supplied with arsenic-safe water (<50 μg L(-1)). Out of 94 (Group-1A) study participants using water with arsenic level <50 μg L(-1), 72 participants (Group-1B) were taking water with arsenic level <10 μg L(-1). Multiple regressions analysis conducted on the Group-1A participants showed that daily arsenic dose from water and diet were found to be significantly positively associated with urinary arsenic level. However, daily arsenic dose from diet was found to be significantly positively associated with urinary arsenic level in Group-1B participants only, but no significant association was found with arsenic dose from water in this group. In a separate analysis, out of 68 participants with arsenic exposure through diet only, urinary arsenic concentration was found to correlate positively (r = 0.573) with dietary arsenic in 45 participants with skin lesion while this correlation was insignificant (r = 0.007) in 23 participants without skin lesion. Our study suggested that dietary arsenic intake was a potential pathway of arsenic exposure even where arsenic intake through water was reduced significantly in arsenic endemic region in West Bengal. Observation of variation in urinary arsenic excretion in arsenic-exposed subjects with and without skin lesion needed further study.

  19. Chronic arsenic toxicity: studies in West Bengal, India.

    PubMed

    Guha Mazumder, Debendranath; Dasgupta, U B

    2011-09-01

    Chronic arsenic toxicity (arsenicosis) as a result of drinking arsenic-contaminated groundwater is a major environmental health hazard throughout the world, including India. A lot of research on health effects, including genotoxic effect of chronic arsenic toxicity in humans, have been carried out in West Bengal during the last 2 decades. A review of literature including information available from West Bengal has been made to characterize the problem. Scientific journals, monographs, and proceedings of conferences with regard to human health effects, including genotoxicity, of chronic arsenic toxicity have been reviewed. Pigmentation and keratosis are the specific skin diseases characteristic of chronic arsenic toxicity. However, in West Bengal, it was found to produce various systemic manifestations, such as chronic lung disease, characterized by chronic bronchitis, chronic obstructive and/or restrictive pulmonary disease, and bronchiectasis; liver diseases, such as non cirrhotic portal fibrosis; polyneuropathy; peripheral vascular disease; hypertension; nonpitting edema of feet/hands; conjunctival congestion; weakness; and anemia. High concentrations of arsenic, greater than or equal to 200 μg/L, during pregnancy were found to be associated with a sixfold increased risk for stillbirth. Cancers of skin, lung, and urinary bladder are the important cancers associated with this toxicity. Of the various genotoxic effects of arsenic in humans, chromosomal aberration and increased frequency of micronuclei in different cell types have been found to be significant. Various probable mechanisms have been incriminated to cause DNA damage because of chronic arsenic toxicity. The results of the study in West Bengal suggest that deficiency in DNA repair capacity, perturbation of methylation of promoter region of p53 and p16 genes, and genomic methylation alteration may be involved in arsenic-induced disease manifestation in humans. P53 polymorphism has been found to be

  20. Association of Cardiometabolic Genes with Arsenic Metabolism Biomarkers in American Indian Communities: The Strong Heart Family Study (SHFS)

    PubMed Central

    Balakrishnan, Poojitha; Vaidya, Dhananjay; Franceschini, Nora; Voruganti, V. Saroja; Gribble, Matthew O.; Haack, Karin; Laston, Sandra; Umans, Jason G.; Francesconi, Kevin A.; Goessler, Walter; North, Kari E.; Lee, Elisa; Yracheta, Joseph; Best, Lyle G.; MacCluer, Jean W.; Kent, Jack; Cole, Shelley A.; Navas-Acien, Ana

    2016-01-01

    Background: Metabolism of inorganic arsenic (iAs) is subject to inter-individual variability, which is explained partly by genetic determinants. Objectives: We investigated the association of genetic variants with arsenic species and principal components of arsenic species in the Strong Heart Family Study (SHFS). Methods: We examined variants previously associated with cardiometabolic traits (~ 200,000 from Illumina Cardio MetaboChip) or arsenic metabolism and toxicity (670) among 2,428 American Indian participants in the SHFS. Urine arsenic species were measured by high performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and percent arsenic species [iAs, monomethylarsonate (MMA), and dimethylarsinate (DMA), divided by their sum × 100] were logit transformed. We created two orthogonal principal components that summarized iAs, MMA, and DMA and were also phenotypes for genetic analyses. Linear regression was performed for each phenotype, dependent on allele dosage of the variant. Models accounted for familial relatedness and were adjusted for age, sex, total arsenic levels, and population stratification. Single nucleotide polymorphism (SNP) associations were stratified by study site and were meta-analyzed. Bonferroni correction was used to account for multiple testing. Results: Variants at 10q24 were statistically significant for all percent arsenic species and principal components of arsenic species. The index SNP for iAs%, MMA%, and DMA% (rs12768205) and for the principal components (rs3740394, rs3740393) were located near AS3MT, whose gene product catalyzes methylation of iAs to MMA and DMA. Among the candidate arsenic variant associations, functional SNPs in AS3MT and 10q24 were most significant (p < 9.33 × 10–5). Conclusions: This hypothesis-driven association study supports the role of common variants in arsenic metabolism, particularly AS3MT and 10q24. Citation: Balakrishnan P, Vaidya D, Franceschini N, Voruganti

  1. Low dose of arsenic trioxide triggers oxidative stress in zebrafish brain: expression of antioxidant genes.

    PubMed

    Sarkar, Shuvasree; Mukherjee, Sandip; Chattopadhyay, Ansuman; Bhattacharya, Shelley

    2014-09-01

    Occurrence of arsenic in the aquatic environment of West Bengal (India), Bangladesh and other countries are of immediate environmental concern. In the present study, zebrafish (Danio rerio) was used as a model to investigate oxidative stress related enzyme activities and expression of antioxidant genes in the brain to 50µg/L arsenic trioxide for 90 days. In treated fish, generation of reactive oxygen species (ROS), malondialdehyde (MDA) and conjugated diene (CD) showed a triphasic response attaining a peak at the end of the exposure. In addition, a gradual increase in GSH level was noted until 60 days and at 90 days, a sudden fall was recorded which heightened arsenic toxicity. However, GSH level does not correlate well with the glutathione reductase (GR) activity. Generation of ROS in zebrafish brain due to As2O3 exposure was further evidenced by significant alteration of glutathione peroxidase (GPx) and catalase (CAT) activity, which converts H2O2 to water and helps in detoxication. Moreover, enhanced mRNA level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in As2O3 exposed zebrafish indicates a protective role of Nrf2. kelch-like ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, inversely correlates with the mRNA expression of Nrf2. As2O3 induced toxicity was also validated by the alteration in NRF2 and NRF2 dependent expression of proteins such as heme oxygenase1 (HO1) and NAD(P)H dehydrogenase quinone1 (NQO1). The mRNA expression of glutathione peroxidase (Gpx1), catalase (Cat), manganese superoxide dismutase (Mn-Sod), copper/zinc superoxide dismutase (Cu/Zn Sod) and cytochrome c oxidase1 (Cox1) were also up regulated. The expression of uncoupling protein 2 (Ucp2), an important mitochondrial enzyme was also subdued in arsenic exposed zebrafish. The oxidative stress induced by arsenic also cause reduced mRNA expression of B-cell lymphoma 2 (Bcl2) present in the inner mitochondrial membrane and thereby indicating onset of apoptosis in

  2. 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.

  3. The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area

    SciTech Connect

    Huang, Chao-Yuan; Su, Chien-Tien; Chu, Jan-Show; Huang, Shu-Pin; Pu, Yeong-Shiau; Yang, Hsiu-Yuan; Chung, Chi-Jung; Wu, Chia-Chang; Hsueh, Yu-Mei

    2011-12-15

    Our recent study demonstrated the increased risk of renal cell carcinoma (RCC) associated with high urinary total arsenic levels among people living in a low arsenic exposure area. Genomic instability is important in arsenic carcinogenesis. This study evaluated the relationship between the polymorphisms of p53, p21, and MDM2, which plays a role in gene stability, and the arsenic-related RCC risk. Here, we found that p53 Pro/Pro genotype and MDM2 SNP309 GG genotype significantly increased RCC risk compared to the p53 Arg/Arg genotype and MDM2 SNP309 TT genotype. RCC patients with the p53Arg/Arg genotype had a signicantly low percentage of inorganic arsenic, a low percentage of monomethylarsonic acid (MMA), and a high percentage of dimethylarsinic acid (DMA), which indicates efcient arsenic methylation capacity. Subjects with the p53 Arg/Pro + Pro/Pro genotype or MDM2 SNP309 TG + GG genotype, in conjunction with high urinary total arsenic ({>=} 14.02 {mu}g/L), had a signicantly higher RCC risk than those with the p53 Arg/Arg or MDM2 SNP309 TT genotypes and low urinary total arsenic. Taken together, this is the first study to show that a variant genotype of p53 Arg{sup 72}Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area. -- Highlights: Black-Right-Pointing-Pointer Subjects with p53 Pro/Pro or MDM2 GG genotype significantly increased RCC risk. Black-Right-Pointing-Pointer A significant multiplicative joint effect of p53 and p21 on RCC risk. Black-Right-Pointing-Pointer RCC patients with p53 Arg/Arg genotype had efficient arsenic methylation capacity. Black-Right-Pointing-Pointer Joint effect of p53 or MDM2 genotype and high urinary total arsenic on RCC risk.

  4. Arsenic metabolites affect expression of the neurofilament and tau genes: an in-vitro study into the mechanism of arsenic neurotoxicity.

    PubMed

    Vahidnia, A; van der Straaten, R J H M; Romijn, F; van Pelt, J; van der Voet, G B; de Wolff, F A

    2007-09-01

    Neurological studies indicate that the central (CNS) and peripheral nervous system (PNS) may be affected by arsenic (As). As-exposed patients show significantly lower nerve conduction velocities (NCVs) in their peripheral nerves in comparison to healthy subjects. As may play a role in the disruption of neuroskeletal integrity, but the mechanisms by which it exerts a toxic effect on the peripheral and central nervous system are still unclear. In the present study, we examined the neurotoxic effects of various arsenic metabolites (iAs(III), iAs(V), MMA(V) and DMA(V)) on two different cell lines derived from the peripheral (ST-8814) and central (SK-N-SH) nervous system. The effects of the arsenic metabolites were examined on the relative quantification levels of the cytoskeletal genes, neurofilament-light (NEFL), neurofilament-medium (NEF3), neurofilament-heavy (NEFH) and microtubule-associated protein-tau (MAPT), using real-time PCR. Our results show that iAs(III) and iAs(V) have no significant effects on either cell lines. On the other hand, MMA(V) and DMA(V) cause significant changes in expression levels of NEF3 and NEFL genes, while the expression level of the NEFH gene is significantly increased in both cell lines.

  5. Higher urinary heavy metal, phthalate, and arsenic but not parabens concentrations in people with high blood pressure, U.S. NHANES, 2011-2012.

    PubMed

    Shiue, Ivy

    2014-06-05

    Link between environmental chemicals and human health has emerged but not been completely examined in risk factors. Therefore, it was aimed to study the relationships of different sets of urinary environmental chemical concentrations and risk of high blood pressure (BP) in a national, population-based study. Data were retrieved from United States National Health and Nutrition Examination Surveys, 2011-2012 including demographics, BP readings, and urinary environmental chemical concentrations. Analyses included chi-square test, t-test and survey-weighted logistic regression modeling. After full adjustment (adjusting for urinary creatinine, age, sex, ethnicity, and body mass index), urinary cesium (OR 1.56, 95%CI 1.11-2.20, P = 0.014), molybden (OR 1.46, 95%CI 1.06-2.01, P = 0.023), manganese (OR 1.42, 95%CI 1.09-1.86, P = 0.012), lead (OR 1.58, 95%CI 1.28-1.96, P < 0.001), tin (OR 1.44, 95%CI 1.25-1.66, P < 0.001), antimony (OR 1.39, 95%CI 1.10-1.77, P = 0.010), and tungsten (OR 1.49, 95%CI 1.25-1.77, P < 0.001) concentrations were observed to be associated with high BP. People with higher urinary mono-2-ethyl-5-carboxypentyl phthalate (OR 1.33, 95%CI 1.00-1.62, P = 0.006), mono-n-butyl phthalate (OR 1.35, 95%CI 1.13-1.62, P = 0.002), mono-2-ethyl-5-hydroxyhexyl (OR 1.25, 95%CI 1.05-1.49, P = 0.014), mono-n-methyl phthalate (OR 1.26, 95%CI 1.07-1.48, P = 0.007), mono-2-ethyl-5-oxohexyl (OR 1.25, 95%CI 1.07-1.48, P = 0.009), and monobenzyl phthalate (OR 1.40, 95%CI 1.15-1.69, P = 0.002) tended to have high BP as well. However, there are no clear associations between environmental parabens and high BP, nor between pesticides and high BP. In addition, trimethylarsine oxide (OR 2.47, 95%CI 1.27-4.81, P = 0.011) and dimethylarsonic acid concentrations (OR 1.42, 95%CI 1.12-1.79, P = 0.006) were seen to be associated with high BP. In sum, urinary heavy metal, phthalate, and arsenic concentrations were associated with high BP, although the causal effect cannot be

  6. 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

  7. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells.

    PubMed

    Stueckle, Todd A; Lu, Yongju; Davis, Mary E; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B; Rojanasakul, Yon

    2012-06-01

    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 6month 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.

  8. Impact of early developmental arsenic exposure on promotor CpG-island methylation of genes involved in neuronal plasticity.

    PubMed

    Martínez, Liborio; Jiménez, Verónica; García-Sepúlveda, Christian; Ceballos, Fátima; Delgado, Juan Manuel; Niño-Moreno, Perla; Doniz, Lesly; Saavedra-Alanís, Víctor; Castillo, Claudia G; Santoyo, Martha E; González-Amaro, Roberto; Jiménez-Capdeville, María E

    2011-04-01

    Epigenetic mechanisms are crucial to regulate the expression of different genes required for neuronal plasticity. Neurotoxic substances such as arsenic, which induces cognitive deficits in exposed children before any other manifestation of toxicity, could interfere with the epigenetic modulation of neuronal gene expression required for learning and memory. This study assessed in Wistar rats the effects that developmental arsenic exposure had on DNA methylation patterns in hippocampus and frontal cortex. Animals were exposed to arsenic in drinking water (3 and 36ppm) from gestation until 4 months of age, and DNA methylation in brain cells was determined by flow cytometry, immunohistochemistry and methylation-specific polymerase chain reaction (PCR) of the promoter regions of reelin (RELN) and protein phosphatase 1 (PP1) at 1, 2, 3 and 4 months of age. Immunoreactivity to 5 methyl-cytosine was significantly higher in the cortex and hippocampus of exposed animals compared to controls at 1 month, and DNA hypomethylation was observed the following months in the cortex at high arsenic exposure. Furthermore, we observed a significant increase in the non-methylated form of PP1 gene promoter at 2 and 3 months of age, either in cortex or hippocampus. In order to determine whether this exposure level is associated with memory deficits, a behavioral test was performed at the same age points, revealing progressive and dose-dependent deficits of fear memory. Our results demonstrate alterations of the methylation pattern of genes involved in neuronal plasticity in an animal model of memory deficit associated with arsenic exposure.

  9. 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...

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

    SciTech Connect

    Muñoz, Alexandra; Chervona, Yana; Hall, Megan; Kluz, Thomas; Gamble, Mary V.; Costa, Max

    2015-05-01

    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. 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

  11. Polymorphisms in maternal folate pathway genes interact with arsenic in drinking water to influence risk of myelomeningocele

    PubMed Central

    Mazumdar, Maitreyi; Valeri, Linda; Rodrigues, Ema G.; Hasan, Md Omar Sharif Ibne; Hamid, Rezina; Paul, Ligi; Selhub, Jacob; Silva, Fareesa; Mostofa, MdGolam; Quamruzzaman, Quazi; Rahman, Mahmuder; Christiani, David C.

    2015-01-01

    Background Arsenic induces neural tube defects in many animal models. Additionally, studies have shown that mice with specific genetic defects in folate metabolism and transport are more susceptible to arsenic-induced neural tube defects. We sought to determine whether 14 single-nucleotide polymorphisms in genes involved in folate metabolism modified the effect of exposure to drinking water contaminated with inorganic arsenic and posterior neural tube defect (myelomeningocele) risk. Methods Fifty-four mothers of children with myelomeningocele and 55 controls were enrolled through clinical sites in rural Bangladesh in a case-control study of the association between environmental arsenic exposure and risk of myelomeningocele. We assessed participants for level of myelomeningocele, administered questionnaires, conducted biological and environmental sample collection, and performed genotyping. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure inorganic arsenic concentration in drinking water. Candidate single-nucleotide polymorphisms were identified through review of the literature. Results Drinking water inorganic arsenic concentration was associated with increased risk of myelomeningocele for participants with 4 of the 14 studied single-nucleotide polymorphisms in genes involved in folate metabolism: the AA/AG genotype of rs2236225 (MTHFD1), the GG genotype of rs1051266 (SLC19A1), the TT genotype of rs7560488 (DNMT3A), and the GG genotype of rs3740393 (AS3MT) with adjusted OR of 1.13, 1.31, 1.20, and 1.25 for rs2236225, rs1051266, rs7560488, and rs3740393, respectively. Conclusions Our results support the hypothesis that environmental arsenic exposure increases the risk of myelomeningocele via interaction with folate metabolic pathways. PMID:26250961

  12. Molecular detection of virulence genes as markers in Pseudomonas aeruginosa isolated from urinary tract infections.

    PubMed

    Sabharwal, Neha; Dhall, Shriya; Chhibber, Sanjay; Harjai, Kusum

    2014-01-01

    Catheter associated urinary tract infections by P. aeruginosa are related to variety of complications. Quorum sensing and related circuitry guard its virulence potential. Though P. aeruginosa accounts for an appreciable amount of virulence factors, this organism is highly unstable phenotypically. Thus, genotyping of clinical isolates of P. aeruginosa is of utmost importance for understanding the epidemiology of infection. This may contribute towards development of immunotherapeutic approaches against this multi drug resistant pathogen. Moreover, no epidemiological study has been reported yet on uroisolates of P. aeruginosa. Thus this study was planned to obtain information regarding presence, distribution and rate of occurrence of quorum sensing and some associated virulence genes at genetic level. The profiling of quorum sensing genes lasI, lasR, rhlI, rhlR and virulence genes like toxA, aprA, rhlAB, plcH, lasB and fliC of twelve strains of P. aeruginosa isolated from patients with UTIs was done by direct PCR. The results showed variable distribution of quorum sensing genes and virulence genes. Their percentage occurrence may be specifically associated with different levels of intrinsic virulence and pathogenicity in urinary tract. Such information can help in identifying these virulence genes as useful diagnostic markers for clinical P. aeruginosa strains isolated from UTIs.

  13. Arsenic and phosphate rock impacted the abundance and diversity of bacterial arsenic oxidase and reductase genes in rhizosphere of As-hyperaccumulator Pteris vittata.

    PubMed

    Han, Yong-He; Fu, Jing-Wei; Xiang, Ping; Cao, Yue; Rathinasabapathi, Bala; Chen, Yanshan; Ma, Lena Q

    2017-01-05

    Microbially-mediated arsenic (As) transformation in soils affects As speciation and plant uptake. However, little is known about the impacts of As on bacterial communities and their functional genes in the rhizosphere of As-hyperaccumulator Pteris vittata. In this study, arsenite (AsIII) oxidase genes (aroA-like) and arsenate (AsV) reductase genes (arsC) were amplified from three soils, which were amended with 50mgkg(-1) As and/or 1.5% phosphate rock (PR) and grew P. vittata for 90 d. The aroA-like genes in the rhizosphere were 50 times more abundant than arsC genes, consistent with the dominance of AsV in soils. According to functional gene alignment, most bacteria belonged to α-, β- and γ-Proteobacteria. Moreover, aroA-like genes showed a higher biodiversity than arsC genes based on clone library analysis and could be grouped into nine clusters based on terminal restriction fragment length polymorphism (T-RFLP) analysis. Besides, AsV amendment elevated aroA-like gene diversity, but decreased arsC gene diversity. Redundancy analysis indicated that soil pH, available Ca and P, and AsV concentration were key factors driving diverse compositions in aroA-like gene community. This work identified new opportunities to screen for As-oxidizing and/or -reducing bacteria to aid phytoremediation of As-contaminated soils.

  14. Risk of carotid atherosclerosis associated with genetic polymorphisms of apolipoprotein E and inflammatory genes among arsenic exposed residents in Taiwan

    SciTech Connect

    Hsieh, Y.-C.; Hsieh, F.-I; Lien, L.-M.; Chou, Y.-L.; Chiou, H.-Y. Chen, C.-J.

    2008-02-15

    Arsenic had been reported to be associated with carotid atherosclerosis. However, there were few studies to evaluate the association between the susceptible gene of lipid metabolism and inflammation and carotid atherosclerosis among arsenic exposure residents. The aim of the study was to investigate the associations between the genetic polymorphisms of APOE and MCP-1 and the risk of carotid atherosclerosis among residents of Lanyang Basin in Taiwan which was a newly confirmed arsenic-endemic area. In total, 479 residents who had been genotyped of these two genes and examined the severity of carotid atherosclerosis were included in this study. The study subjects with carotid intima media thickness (IMT) {>=} 1.0 mm or with the observable plaque in the extracranial carotid artery were diagnosed as carotid atherosclerosis. A significantly age- and gender-adjusted odds ratio of 2.0 for the development of carotid atherosclerosis was observed in study subjects with {epsilon}4 allele of APOE than those without {epsilon}4 allele. Compared with study subjects who carried wild genotypes of APOE and MCP-1, those with both risk genotypes of APOE and MCP-1 had 2.5-fold risk of carotid atherosclerosis after adjustment for age and gender, revealing a significant dose-response relationship between number of risk genotypes of these genes and risk of carotid atherosclerosis. Additionally, study subjects with two risk genotypes of APOE and MCP-1 and either had ingested well water contained arsenic level > 10 {mu}g/L or had arsenic exposure > 0.22 mg/L-year would have strikingly highest risk of 10.3-fold and 15.7-fold, respectively, for the development carotid atherosclerosis, showing significant joint effect of arsenic exposure and risk genotypes of APOE and MCP-1.

  15. Biological and behavioral factors modify biomarkers of arsenic exposure in a U.S. population.

    PubMed

    Calderon, Rebecca L; Hudgens, Edward E; Carty, Cara; He, Bin; Le, X Chris; Rogers, John; Thomas, David J

    2013-10-01

    Although consumption of drinking water contaminated with inorganic arsenic is usually considered the primary exposure route, aggregate exposure to arsenic depends on direct consumption of water, use of water in food preparation, and the presence in arsenicals in foods. To gain insight into the effects of biological and behavioral factors on arsenic exposure, we determined arsenic concentrations in urine and toenails in a U.S. population that uses public or private water supplies containing inorganic arsenic. Study participants were 904 adult residents of Churchill County, Nevada, whose home tap water supplies contained <3 to about 1200 µg of arsenic per liter. Biomarkers of exposure for this study were summed urinary concentrations of inorganic arsenic and its methylated metabolites (speciated arsenical), of all urinary arsenicals (total arsenical), and of all toenail arsenicals (total arsenical). Increased tap water arsenic concentration and consumption were associated with significant upward trends for urinary speciated and total and toenail total arsenical concentrations. Significant gender differences in concentrations of speciated and total arsenicals in urine and toenails reflected male-female difference in water intake. Both recent and higher habitual seafood consumption significantly increased urinary total but not speciated arsenical concentration. In a stepwise general linear model, seafood consumption significantly predicted urinary total arsenical but not urinary speciated or toenail total arsenical concentrations. Smoking behavior significantly predicted urinary speciated or total arsenical concentration. Gender, tap water arsenic concentration, and primary drinking water source significantly predicted urinary speciated and total concentrations and toenail total arsenical concentrations. These findings confirm the primacy of home tap water as a determinant of arsenic concentration in urine and toenails. However, biological and behavioral factors can

  16. Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study

    PubMed Central

    Savlı, Hakan; Galimberti, Sara; Sünnetçi, Deniz; Canestraro, Martina; Palumbo, Giuseppe; Nagy, Balint; Raimondo, Francesco Di; Petrini, Mario

    2015-01-01

    Objective: We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39. Materials and Methods: Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR. Results: Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor) and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings. Conclusion: Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-κB was observed as an important modulator in leukemic transformation of MDS. PMID:25913414

  17. Gene Expression of Normal Human Epidermal Keratinocytes Modulated by Trivalent Arsenicals

    EPA Science Inventory

    Chronic exposure to inorganic arsenic (iAs) is associated with the development of benign and malignant human skin lesions including nonmelanoma skin cancers. The precise arsenical form(s) responsible for this carcinogenic effect are unknown, although trivalent inorganic arsenic (...

  18. 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...

  19. FOLATE DEFICIENCY ENHANCES ARSENIC EFFECTS ON EXPRESSION OF GENES INVOLVED IN EPIDERMAL DIFFERENTIATION

    EPA Science Inventory

    Chronic arsenic exposure in humans is associated with cancers of the skin, lung, and bladder. There is evidence that folate deficiency may increase susceptibility to arsenic¿s effects, including arsenic-induced skin lesions. K6/ODC mice develop skin tumors when exposed to 10 ppm ...

  20. Urinary delta-ALA: a potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese.

    PubMed

    Andrade, Vanda; Mateus, M Luísa; Batoréu, M Camila; Aschner, Michael; dos Santos, A P Marreilha

    2013-09-01

    Lead (Pb), arsenic (As) and manganese (Mn) are neurotoxic elements that often occur in mixtures for which practically no information is available on biomarkers (BMs) for the evaluation of exposure/effects. Exposures to these metals may increase delta-aminolevulinic acid (delta-ALA), which in itself may potentiate neurotoxicity. The objective of this study was to investigate the utility of urinary delta-ALA (delta-ALA-U) levels as BM of exposure and/or neurotoxic effects induced by this mixture. Five groups of Wistar rats were treated for 8 days with Pb (5mg/kg), As (60mg/L), Mn (10mg/kg), the 3-metal mixture (same doses of the single metals), and control group. Motor activity was evaluated and 24-h urine collected before and after the treatment. 24-hours (h) after the last dose, the rats were sacrificed and the brains removed for analyses. Delta-ALA and metal levels were determined in brain and urine. Co-treated rats showed a significant (p<0.05) correlation between increased Pb, As, Mn and delta-ALA levels in the brain and decreased motor activity. Delta-ALA-U concentrations were higher in the mixture-treated group than the sum of the delta-ALA-U levels in each single-treated groups and discriminated (p<0.05) between the mixture and untreated rats. Moreover, delta-ALA-U was correlated (p<0.05) with brain delta-ALA levels. These results establish that treatments with this metal mixture exacerbate behavioral dysfunction, increasing most prominently brain Pb levels. This study is the first to establish that delta-ALA-U levels represent a sensitive BM of exposure/neurotoxic effect to this metal mixture.

  1. Urinary delta-ALA: a potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese

    PubMed Central

    Andrade, Vanda; Mateus, M. Luísa; Batoréu, M. Camila; Aschner, Michael; Marreilha dos Santos, A.P.

    2013-01-01

    Lead (Pb), arsenic (As) and manganese (Mn) are neurotoxic elements that often occur in mixtures for which practically no information is available on biomarkers (BMs) for the evaluation of exposure/effects. Exposures to these metals may increase delta-aminolevulinic acid (delta-ALA), which in itself may potentiate neurotoxicity. The objective of this study was to investigate the utility of urinary delta-ALA (delta-ALA-U) levels as BM of exposure and/or neurotoxic effects induced by this mixture. Five groups of Wistar rats were treated for 8 days with Pb (5 mg/kg), As (60 mg/L), Mn (10 mg/kg), the 3-metal mixture (same doses of the single metals), and control group. Motor activity was evaluated and 24-h urine collected before and after the treatment. 24-hours (h) after the last dose, the rats were sacrificed and the brains removed for analyses. Delta-ALA and metal levels were determined in brain and urine. Co-treated rats showed a significant (p<0.05) correlation between increased Pb, As, Mn and delta-ALA levels in the brain and decreased motor activity. Delta-ALA-U concentrations were higher in the mixture-treated group than the sum of the delta-ALA-U levels in each single-treated groups and discriminated (p<0.05) between the mixture and untreated rats. Moreover, delta-ALA-U was correlated (p<0.05) with brain delta-ALA levels. These results establish that treatments with this metal mixture exacerbate behavioral dysfunction, increasing most prominently brain Pb levels. This study is the first to establish that delta-ALA-U levels represent a sensitive BM of exposure/neurotoxic effect to this metal mixture. PMID:23764341

  2. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    SciTech Connect

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    2012-06-01

    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 6 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. Highlights: ► Chronic As{sub 2}O

  3. Analysis of Genes Involved in Arsenic Resistance in Corynebacterium glutamicum ATCC 13032†

    PubMed Central

    Ordóñez, Efrén; Letek, Michal; Valbuena, Noelia; Gil, José A.; Mateos, Luis M.

    2005-01-01

    Corynebacterium glutamicum is able to grow in media containing up to 12 mM arsenite and 500 mM arsenate and is one of the most arsenic-resistant microorganisms described to date. Two operons (ars1 and ars2) involved in arsenate and arsenite resistance have been identified in the complete genome sequence of Corynebacterium glutamicum. The operons ars1 and ars2 are located some distance from each other in the bacterial chromosome, but they are both composed of genes encoding a regulatory protein (arsR), an arsenite permease (arsB), and an arsenate reductase (arsC); operon ars1 contains an additional arsenate reductase gene (arsC1′) located immediately downstream from arsC1. Additional arsenite permease and arsenate reductase genes (arsB3 and arsC4) scattered on the chromosome were also identified. The involvement of ars operons in arsenic resistance in C. glutamicum was confirmed by gene disruption experiments of the three arsenite permease genes present in its genome. Wild-type and arsB3 insertional mutant C. glutamicum strains were able to grow with up to 12 mM arsenite, whereas arsB1 and arsB2 C. glutamicum insertional mutants were resistant to 4 mM and 9 mM arsenite, respectively. The double arsB1-arsB2 insertional mutant was resistant to only 0.4 mM arsenite and 10 mM arsenate. Gene amplification assays of operons ars1 and ars2 in C. glutamicum revealed that the recombinant strains containing the ars1 operon were resistant to up to 60 mM arsenite, this being one of the highest levels of bacterial resistance to arsenite so far described, whereas recombinant strains containing operon ars2 were resistant to only 20 mM arsenite. Northern blot and reverse transcription-PCR analysis confirmed the presence of transcripts for all the ars genes, the expression of arsB3 and arsC4 being constitutive, and the expression of arsR1, arsB1, arsC1, arsC1′, arsR2, arsB2, and arsC2 being inducible by arsenite. PMID:16204540

  4. Evaluating long-term cellular effects of the arsenic species thio-DMA(V): qPCR-based gene expression as screening tool.

    PubMed

    Ebert, Franziska; Thomann, Marlies; Witt, Barbara; Müller, Sandra M; Meyer, Sören; Weber, Till; Christmann, Markus; Schwerdtle, Tanja

    2016-09-01

    Thio-dimethylarsinic acid (thio-DMA(V)) is a human urinary metabolite of the class 1 human carcinogen inorganic arsenic as well as of arsenosugars. Thio-DMA(V) exerts strong cellular toxicity, whereas its toxic modes of action are not fully understood. For the first time, this study characterises the impact of a long-term (21days) in vitro incubation of thio-DMA(V) on the expression of selected genes related to cell death, stress response, epigenetics and DNA repair. The observed upregulation of DNMT1 might be a cellular compensation to counterregulate the in a very recent study observed massive global DNA hypomethylation after chronic thio-DMA(V) incubation. Moreover, our data suggest that chronic exposure towards subcytotoxic, pico- to nanomolar concentrations of thio-DMA(V) causes a stress response in human urothelial cells. The upregulation of genes encoding for proteins of DNA repair (Apex1, Lig1, XRCC1, DDB2, XPG, ATR) as well as damage response (GADD45A, GADD45G, Trp53) indicate a potential genotoxic risk emanating from thio-DMA(V) after long-term incubation.

  5. The immune responses and expression of metallothionein (MT) gene and heat shock protein 70 (HSP 70) in juvenile rockfish, Sebastes schlegelii, exposed to waterborne arsenic (As(3+)).

    PubMed

    Kim, Jun-Hwan; Kang, Ju-Chan

    2016-10-01

    Juvenile rockfish, Sebastes schlegelii (mean length 16.4±1.9cm, and mean weight 71.6±6.4g) were exposed for 20days with the different levels of waterborne arsenic concentration (0, 50, 100, 200 and 400μg/L). The plasma cortisol of S. schlegelii was significantly increased by the waterborne arsenit exposure. In the immune responses, the immunoglobulin M (Ig M) and lysozyme activity of S. schlegelii were significantly increased by the waterborne arsenic exposure. The acetylcholinesterase (AChE) activity of S. schlegelii was inhibited by the waterborne arsenic exposure. The substantial increases in the gene expression such as metallothionein (MT) and heat shock protein 70 (HSP 70) were observed by the waterborne arsenic exposure. The results demonstrated that waterborne arsenic exposure can induce the significant alterations in the immune responses and specific gene expression of S. schlegelii.

  6. Transcriptome profiling of genes and pathways associated with arsenic toxicity and tolerance in Arabidopsis

    PubMed Central

    2014-01-01

    Background Arsenic (As) is a toxic metalloid found ubiquitously in the environment and widely considered an acute poison and carcinogen. However, the molecular mechanisms of the plant response to As and ensuing tolerance have not been extensively characterized. Here, we report on transcriptional changes with As treatment in two Arabidopsis accessions, Col-0 and Ws-2. Results The root elongation rate was greater for Col-0 than Ws-2 with As exposure. Accumulation of As was lower in the more tolerant accession Col-0 than in Ws-2. We compared the effect of As exposure on genome-wide gene expression in the two accessions by comparative microarray assay. The genes related to heat response and oxidative stresses were common to both accessions, which indicates conserved As stress-associated responses for the two accessions. Most of the specific response genes encoded heat shock proteins, heat shock factors, ubiquitin and aquaporin transporters. Genes coding for ethylene-signalling components were enriched in As-tolerant Col-0 with As exposure. A tolerance-associated gene candidate encoding Leucine-Rich Repeat receptor-like kinase VIII (LRR-RLK VIII) was selected for functional characterization. Genetic loss-of-function analysis of the LRR-RLK VIII gene revealed altered As sensitivity and the metal accumulation in roots. Conclusions Thus, ethylene-related pathways, maintenance of protein structure and LRR-RLK VIII-mediated signalling may be important mechanisms for toxicity and tolerance to As in the species. Here, we provide a comprehensive survey of global transcriptional regulation for As and identify stress- and tolerance-associated genes responding to As. PMID:24734953

  7. Bacteria and Genes Involved in Arsenic Speciation in Sediment Impacted by Long-Term Gold Mining

    PubMed Central

    Costa, Patrícia S.; Scholte, Larissa L. S.; Reis, Mariana P.; Chaves, Anderson V.; Oliveira, Pollyanna L.; Itabayana, Luiza B.; Suhadolnik, Maria Luiza S.; Barbosa, Francisco A. R.; Chartone-Souza, Edmar; Nascimento, Andréa M. A.

    2014-01-01

    The bacterial community and genes involved in geobiocycling of arsenic (As) from sediment impacted by long-term gold mining were characterized through culture-based analysis of As-transforming bacteria and metagenomic studies of the arsC, arrA, and aioA genes. Sediment was collected from the historically gold mining impacted Mina stream, located in one of the world’s largest mining regions known as the “Iron Quadrangle”. A total of 123 As-resistant bacteria were recovered from the enrichment cultures, which were phenotypically and genotypically characterized for As-transformation. A diverse As-resistant bacteria community was found through phylogenetic analyses of the 16S rRNA gene. Bacterial isolates were affiliated with Proteobacteria, Firmicutes, and Actinobacteria and were represented by 20 genera. Most were AsV-reducing (72%), whereas AsIII-oxidizing accounted for 20%. Bacteria harboring the arsC gene predominated (85%), followed by aioA (20%) and arrA (7%). Additionally, we identified two novel As-transforming genera, Thermomonas and Pannonibacter. Metagenomic analysis of arsC, aioA, and arrA sequences confirmed the presence of these genes, with arrA sequences being more closely related to uncultured organisms. Evolutionary analyses revealed high genetic similarity between some arsC and aioA sequences obtained from isolates and clone libraries, suggesting that those isolates may represent environmentally important bacteria acting in As speciation. In addition, our findings show that the diversity of arrA genes is wider than earlier described, once none arrA-OTUs were affiliated with known reference strains. Therefore, the molecular diversity of arrA genes is far from being fully explored deserving further attention. PMID:24755825

  8. Characterization of the ars Gene Cluster from Extremely Arsenic-Resistant Microbacterium sp. Strain A33▿ †

    PubMed Central

    Achour-Rokbani, Asma; Cordi, Audrey; Poupin, Pascal; Bauda, Pascale; Billard, Patrick

    2010-01-01

    The arsenic resistance gene cluster of Microbacterium sp. A33 contains a novel pair of genes (arsTX) encoding a thioredoxin system that are cotranscribed with an unusual arsRC2 fusion gene, ACR3, and arsC1 in an operon divergent from arsC3. The whole ars gene cluster is required to complement an Escherichia coli ars mutant. ArsRC2 negatively regulates the expression of the pentacistronic operon. ArsC1 and ArsC3 are related to thioredoxin-dependent arsenate reductases; however, ArsC3 lacks the two distal catalytic cysteine residues of this class of enzymes. PMID:19966021

  9. 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...

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

    PubMed

    Muñoz, Alexandra; Chervona, Yana; Hall, Megan; Kluz, Thomas; Gamble, Mary V; Costa, Max

    2015-05-01

    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. 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.

  11. Transplacental arsenic plus postnatal 12-O-teradecanoyl phorbol-13-acetate exposures associated with hepatocarcinogenesis induce similar aberrant gene expression patterns in male and female mouse liver

    SciTech Connect

    Liu Jie . E-mail: Liu6@niehs.nih.gov; Xie Yaxiong; Merrick, B. Alex; Shen Jun; Ducharme, Danica M.K.; Collins, Jennifer; Diwan, Bhalchandra A.; Logsdon, Daniel; Waalkes, Michael P.

    2006-06-15

    Our prior work shows that in utero arsenic exposure alone is a complete transplacental carcinogen, producing hepatocellular carcinoma in adult male offspring but not in females. In a follow-up study to potentially promote arsenic-initiated tumors, mice were exposed to arsenic (85 ppm) from gestation day 8 to 18 and then exposed to 12-O-teradecanoyl phorbol-13-acetate (TPA), a well-known tumor promoter after weaning. The dermal application of TPA (2 {mu}g/0.1 ml acetone, twice/week for 21 weeks) after transplacental arsenic did not further increase arsenic-induced liver tumor formation in adult males but significantly increased liver tumor formation in adult females. Thus, for comparison, liver tumors and normal liver samples taken from adult male and female mice at necropsy were analyzed for aberrant gene/protein expression by microarray, real-time RT-PCR and Western blot analysis. Arsenic/TPA treatment resulted in increased expression of {alpha}-fetoprotein, k-ras, c-myc, estrogen receptor-{alpha}, cyclin D1, cdk2na, plasminogen activator inhibitor-1, cytokeratin-8, cytokeratin-18, glutathione S-transferases and insulin-like growth factor binding proteins in liver and liver tumors from both male and female mice. Arsenic/TPA also decreased the expression of BRCA1, betaine-homocysteine methyltransferase, CYP7B1, CYP2F2 and insulin-like growth factor-1 in normal and cancerous livers. Alterations in these gene products were associated with arsenic/TPA-induced liver tumors, regardless of sex. Thus, transplacental arsenic plus postnatal TPA exposure induced similar aberrant gene expression patterns in male and female mouse liver, which are persistent and potentially important to the mechanism of arsenic initiation of hepatocarcinogenesis.

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

    SciTech Connect

    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; and others

    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. - 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

  13. Reduced Expression of MAPK/ERK Genes in Perinatal Arsenic-Exposed Offspring Induced by Glucocorticoid Receptor Deficits

    PubMed Central

    Martinez-Finley, Ebany J.; Goggin, Samantha L.; Labrecque, Matthew T.; Allan, Andrea M.

    2011-01-01

    Changes within the glucocorticoid receptor (GR) cellular signaling pathway were evaluated in adolescent mice exposed to 50 ppb arsenic during gestation. Previously, we reported increased basal plasma corticosterone levels, decreased hippocampal GR levels and deficits in learning and memory performance in perinatal arsenic-exposed mice. The biosynthesis of members of the mitogen-activated protein kinase (MAPK) signaling pathway, known to be involved in learning and memory, is modulated by the binding of GR to glucocorticoid response elements (GREs) in the gene promoters. Two genes of the MAPK pathway, Ras and Raf, contain GREs which are activated upon binding of GRs. We evaluated the activity of GRs at Ras and Raf promoters using chromatin immunoprecipitation and real-time PCR and report decreased binding of the GR at these promoters. An ELISA-based GR binding assay was used to explore whether this decreased binding was restricted to in vivo promoters and revealed no differences in binding of native GR to synthetic GREs. The decreased in vivo GR binding coincides with significantly decreased mRNA levels and slight reductions of protein of both H-Ras and Raf-1 in perinatally arsenic-exposed mice. Nuclear activated extracellular-signal regulated kinase (ERK), a downstream target of Ras and Raf, whose transcriptional targets also play an important role in learning and memory, was decreased in the hippocampus of arsenic-exposed animals when compared to controls. GR-mediated transcriptional deficits in the MAPK/ERK pathway could be an underlying cause of previously reported learning deficits and provide the link to arsenic-induced deficiencies in cognitive development. PMID:21784148

  14. GSTM1 and APE1 genotypes affect arsenic-induced oxidative stress: a repeated measures study

    PubMed Central

    Breton, Carrie V; Kile, Molly L; Catalano, Paul J; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Christiani, David C

    2007-01-01

    Background Chronic arsenic exposure is associated with an increased risk of skin, bladder and lung cancers. Generation of oxidative stress may contribute to arsenic carcinogenesis. Methods To investigate the association between arsenic exposure and oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was evaluated in a cohort of 97 women recruited from an arsenic-endemic region of Bangladesh in 2003. Arsenic exposure was measured in urine, toenails, and drinking water. Drinking water and urine samples were collected on three consecutive days. Susceptibility to oxidative stress was evaluated by genotyping relevant polymorphisms in glutathione-s transferase mu (GSTM1), human 8-oxoguanine glycosylase (hOGG1) and apurinic/apyrimidinic endonuclease (APE1) genes using the Taqman method. Data were analyzed using random effects Tobit regression to account for repeated measures and 8-OHdG values below the detection limit. Results A consistent negative effect for APE1 was observed across water, toenail and urinary arsenic models. APE1 148 glu/glu + asp/glu genotype was associated with a decrease in logged 8-OHdG of 0.40 (95%CI -0.73, -0.07) compared to APE1 148 asp/asp. An association between total urinary arsenic and 8-OHdG was observed among women with the GSTM1 null genotype but not in women with GSTM1 positive. Among women with GSTM1 null, a comparison of the second, third, and fourth quartiles of total urinary arsenic to the first quartile resulted in a 0.84 increase (95% CI 0.27, 1.42), a 0.98 increase (95% CI 033, 1.66) and a 0.85 increase (95% CI 0.27, 1.44) in logged 8-OHdG, respectively. No effects between 8-OHdG and toenail arsenic or drinking water arsenic were observed. Conclusion These results suggest the APE1 variant genotype decreases repair of 8-OHdG and that arsenic exposure is associated with oxidative stress in women who lack a functional GSTM1 detoxification enzyme. PMID:18053222

  15. Colorimetric TMPRSS2-ERG Gene Fusion Detection in Prostate Cancer Urinary Samples via Recombinase Polymerase Amplification.

    PubMed

    Koo, Kevin M; Wee, Eugene J H; Trau, Matt

    2016-01-01

    TMPRSS2 (Exon 1)-ERG (Exon 4) is the most frequent gene fusion event in prostate cancer (PC), and is highly PC-specific unlike the current serum prostate specific antigen (PSA) biomarker. However, TMPRSS2-ERG levels are currently measured with quantitative reverse-transcription PCR (RT-qPCR) which is time-consuming and requires costly equipment, thus limiting its use in clinical diagnostics. Herein, we report a novel rapid, cost-efficient and minimal-equipment assay named "FusBLU" for detecting TMPRSS2-ERG gene fusions from urine. TMPRSS2-ERG mRNA was amplified by isothermal reverse transcription-recombinase polymerase amplification (RT-RPA), magnetically-isolated, and detected through horseradish peroxidase (HRP)-catalyzed colorimetric reaction. FusBLU was specific for TMPRSS2-ERG mRNA with a low visual detection limit of 10(5) copies. We also demonstrated assay readout versatility on 3 potentially useful platforms. The colorimetric readout was detectable by naked eye for a quick yes/no evaluation of gene fusion presence. On the other hand, a more quantitative TMPRSS2-ERG detection was achievable by absorbance/electrochemical measurements. FusBLU was successfully applied to 12 urinary samples and results were validated by gold-standard RT-qPCR. We also showed that sediment RNA was likely the main source of TMPRSS2-ERG mRNA in urinary samples. We believe that our assay is a potential clinical screening tool for PC and could also have wide applications for other disease-related fusion genes.

  16. Colorimetric TMPRSS2-ERG Gene Fusion Detection in Prostate Cancer Urinary Samples via Recombinase Polymerase Amplification

    PubMed Central

    Koo, Kevin M.; Wee, Eugene J.H.; Trau, Matt

    2016-01-01

    TMPRSS2 (Exon 1)-ERG (Exon 4) is the most frequent gene fusion event in prostate cancer (PC), and is highly PC-specific unlike the current serum prostate specific antigen (PSA) biomarker. However, TMPRSS2-ERG levels are currently measured with quantitative reverse-transcription PCR (RT-qPCR) which is time-consuming and requires costly equipment, thus limiting its use in clinical diagnostics. Herein, we report a novel rapid, cost-efficient and minimal-equipment assay named “FusBLU” for detecting TMPRSS2-ERG gene fusions from urine. TMPRSS2-ERG mRNA was amplified by isothermal reverse transcription-recombinase polymerase amplification (RT-RPA), magnetically-isolated, and detected through horseradish peroxidase (HRP)-catalyzed colorimetric reaction. FusBLU was specific for TMPRSS2-ERG mRNA with a low visual detection limit of 105 copies. We also demonstrated assay readout versatility on 3 potentially useful platforms. The colorimetric readout was detectable by naked eye for a quick yes/no evaluation of gene fusion presence. On the other hand, a more quantitative TMPRSS2-ERG detection was achievable by absorbance/electrochemical measurements. FusBLU was successfully applied to 12 urinary samples and results were validated by gold-standard RT-qPCR. We also showed that sediment RNA was likely the main source of TMPRSS2-ERG mRNA in urinary samples. We believe that our assay is a potential clinical screening tool for PC and could also have wide applications for other disease-related fusion genes. PMID:27375789

  17. Gene expression of the arsenic resistance operon in Chromobacterium violaceum ATCC 12472.

    PubMed

    Azevedo, Juliana Simão Nina de; Silva-Rocha, Rafael; Silva, Artur; Peixe Carepo, Marta Sofia; Cruz Schneider, Maria Paula

    2008-02-01

    Chromobacterium violaceum ATCC 12472 presents an arsRCB-type operon, which is involved in arsenic resistance. The regulating protein of this resistance system (ArsR) does not have the small conserved site (ELCVDCL) to link to the metalloid, as observed in Escherichia coli, and is thus considered to be an atypical ArsR protein, like that observed in Acidithiobacillus ferrooxidans. In the present study, the gene expression profile of the ars operon under induction at different concentrations of arsenite - As(III) - was obtained via real-time PCR (TaqMan), by correlating the threshold cycle (Ct) values of induced and uninduced (control) samples. Through linear regression analysis (R2 = 0.9926), the gene expression profile of the ars operon showed clearly that the 0.125 micromol/L concentration of As(III) was sufficient to provoke a 4-fold increase in the resistance system, and a further increase in concentration resulted in an increase of up to 53-fold in transcription rates. The relation between resistance and induction of the ars operon indicates that the increased resistance to As(III) is associated with the increase in the number of transcripts.

  18. 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...

  19. Trichoderma inoculation ameliorates arsenic induced phytotoxic changes in gene expression and stem anatomy of chickpea (Cicer arietinum).

    PubMed

    Tripathi, Pratibha; Singh, Poonam C; Mishra, Aradhana; Chaudhry, Vasvi; Mishra, Sandhya; Tripathi, Rudra D; Nautiyal, Chandra S

    2013-03-01

    Arsenic, a carcinogenic metalloid severely affects plant growth in contaminated areas. Present study shows role of Trichoderma reesei NBRI 0716 (NBRI 0716) in ameliorating arsenic (As) stress on chickpea under greenhouse conditions. Arsenic stress adversely affected seed germination (25%), chlorophyll content (44%) and almost eliminated nodule formation that were significantly restored on NBRI 0716 inoculation. It also restored stem anomalies like reduced trichome turgidity and density, deformation in collenchymatous and sclerenchymatous cells induced by As stress. Semi-quantitative RT-PCR of stress responsive genes showed differential expression of genes involved in synthesis of cell wall degrading enzymes, dormancy termination and abiotic stress. Upregulation of drought responsive genes (DRE, EREBP, T6PS, MIPS, and PGIP), enhanced proline content and shrunken cortex cells in the presence of As suggests that it creates water deficiency in plants and these responses were modulated by NBRI 0716 which provides a protective role. NBRI0716 mediated production of As reductase enzyme in chickpea and thus contributed in As metabolism. The study suggests a multifarious role of NBRI0716 in mediating stress tolerance in chickpea towards As.

  20. A review on environmental factors regulating arsenic methylation in humans

    SciTech Connect

    Tseng, C.-H.

    2009-03-15

    Subjects exposed to arsenic show significant inter-individual variation in urinary patterns of arsenic metabolites but insignificant day-to-day intra-individual variation. The inter-individual variation in arsenic methylation can be partly responsible for the variation in susceptibility to arsenic toxicity. Wide inter-ethnic variation and family correlation in urinary arsenic profile suggest a genetic effect on arsenic metabolism. In this paper the environmental factors affecting arsenic metabolism are reviewed. Methylation capacity might reduce with increasing dosage of arsenic exposure. Furthermore, women, especially at pregnancy, have better methylation capacity than their men counterparts, probably due to the effect of estrogen. Children might have better methylation capacity than adults and age shows inconsistent relevance in adults. Smoking and alcohol consumption might be associated with a poorer methylation capacity. Nutritional status is important in the methylation capacity and folate may facilitate the methylation and excretion of arsenic. Besides, general health conditions and medications might influence the arsenic methylation capacity; and technical problems can cause biased estimates. The consumption of seafood, seaweed, rice and other food with high arsenic contents and the extent of cooking and arsenic-containing water used in food preparation may also interfere with the presentation of the urinary arsenic profile. Future studies are necessary to clarify the effects of the various arsenic metabolites including the trivalent methylated forms on the development of arsenic-induced human diseases with the consideration of the effects of confounding factors and the interactions with other effect modifiers.

  1. Characterization and Transcription of Arsenic Respiration and Resistance Genes During In Situ Uranium Bioremediation

    SciTech Connect

    Giloteaux, L.; Holmes, Dawn E.; Williams, Kenneth H.; Wrighton, Kelly C.; Wilkins, Michael J.; Montgomery, Alison P.; Smith, Jessica A.; Orellana, Roberto; Thompson, Courtney A.; Roper, Thomas J.; Long, Philip E.; Lovley, Derek R.

    2013-02-04

    The possibility of arsenic release and the potential role of Geobacter in arsenic biogeochemistry during in situ uranium bioremediation was investigated because increased availability of organic matter has been associated with substantial releases of arsenic in other subsurface environments. In a field experiment conducted at the Rifle, CO study site, groundwater arsenic concentrations increased when acetate was added. The number of transcripts from arrA, which codes for the alpha subunit of dissimilatory As(V) reductase, and acr3, which codes for the arsenic pump protein Acr3, were determined with quantitative RT-PCR. Most of the arrA (> 60%) and acr3-1 (> 90%) sequences that were recovered were most similar to Geobacter species, while the majority of acr3-2 (>50%) sequences were most closely related to Rhodoferax ferrireducens. Analysis of transcript abundance demonstrated that transcription of acr3-1 by the subsurface Geobacter community was correlated with arsenic concentrations in the groundwater. In contrast, Geobacter arrA transcript numbers lagged behind the major arsenic release and remained high even after arsenic concentrations declined. This suggested that factors other than As(V) availability regulated transcription of arrA in situ even though the presence of As(V) increased transcription of arrA in cultures of G. lovleyi, which was capable of As(V) reduction. These results demonstrate that subsurface Geobacter species can tightly regulate their physiological response to changes in groundwater arsenic concentrations. The transcriptomic approach developed here should be useful for the study of a diversity of other environments in which Geobacter species are considered to have an important influence on arsenic biogeochemistry.

  2. 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.

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

    SciTech Connect

    Steinmaus, Craig; Yuan Yan; Kalman, Dave; Rey, Omar A.; Skibola, Christine F.; Dauphine, Dave; Basu, Anamika; Porter, Kristin E.; Hubbard, Alan; Bates, Michael N.; Smith, Martyn T.; Smith, Allan H.

    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 was 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.

  4. Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.

    PubMed

    Farzan, Shohreh F; Karagas, Margaret R; Jiang, Jieying; Wu, Fen; Liu, Mengling; Newman, Jonathan D; Jasmine, Farzana; Kibriya, Muhammad G; Paul-Brutus, Rachelle; Parvez, Faruque; Argos, Maria; Scannell Bryan, Molly; Eunus, Mahbub; Ahmed, Alauddin; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Slavkovich, Vesna; Graziano, Joseph; Ahsan, Habibul; Chen, Yu

    2015-10-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and mounting evidence indicates that toxicant exposures can profoundly impact on CVD risk. Epidemiologic studies have suggested that arsenic (As) exposure is positively related to increases in blood pressure (BP), a primary CVD risk factor. However, evidence of whether genetic susceptibility can modify the association between As and BP is lacking. In this study, we used mixed effect models adjusted for potential confounders to examine the interaction between As exposure from well water and potential genetic modifiers on longitudinal change in BP over approximately 7years of follow-up in 1137 subjects selected from the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Bangladesh. Genotyping was conducted for 235 SNPs in 18 genes related to As metabolism, oxidative stress and endothelial function. We observed interactions between 44 SNPs with well water As for one or more BP outcome measures (systolic, diastolic, or pulse pressure (PP)) over the course of follow-up. The interaction between CYBA rs3794624 and well water As on annual PP remained statistically significant after correction for multiple comparisons (FDR-adjusted p for interaction=0.05). Among individuals with the rs3794624 variant genotype, well water As was associated with a 2.23mmHg (95% CI: 1.14-3.32) greater annual increase in PP, while among those with the wild type, well water As was associated with a 0.13mmHg (95% CI: 0.02-0.23) greater annual increase in PP. Our results suggest that genetic variability may contribute to As-associated increases in BP over time.

  5. Ethnic differences in five intronic polymorphisms associated with arsenic metabolism within human arsenic (+ 3 oxidation state) methyltransferase (AS3MT) gene

    SciTech Connect

    Fujihara, Junko; Fujii, Yoshimi; Agusa, Tetsuro; Kunito, Takashi; Yasuda, Toshihiro; Moritani, Tamami; Takeshita, Haruo

    2009-01-01

    Human arsenic (+ 3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite, and intronic single-nucleotide polymorphisms (SNPs: G7395A, G12390C, T14215C, T35587C, and G35991A) in the AS3MT gene were shown to be related to inter-individual variation in the arsenic metabolism. In the present study, the genotyping for these SNPs was developed using the polymerase chain reaction and restriction fragment length polymorphism technique. Applying this method, the genotype distribution among the Ovambo, Turkish, Mongolian, Korean, and Japanese populations was investigated, and our results were compared with those from other studies. G7395, G12390, T35587, and A35991 were predominant among the five populations in our study. However, a previous study in Argentina, C12390 and G35991 showed the highest allele frequency among the eight populations studied in other studies. The dominant allele of T14215C differed among populations: the T14215 allele was predominant in Argentina, the allele frequency of C14215 was higher than that of T14215 among Turks, Mongolians, Europeans, and American ancestry. In Korea and Japan, similar allele frequencies were observed in T14215 and C14215. Higher allele frequencies were observed in haplotype G7395/G12390/C14215/T35587 with frequencies of 0.40 (Turks), 0.28 (Mongolians), and 0.23 (Koreans). On the other hand, the allele frequency for G7395/G14215/T35587/A35991 was the highest among the Ovambos (0.32), and the frequency for G7395/G12390/C35587/G35991 was the highest among the Japanese (0.27). It is noteworthy that the Japanese haplotype differs from that of the Koreans and Mongolians, which indicates the importance of investigating other intronic polymorphisms in AS3MT, especially in Asians.

  6. Escherichia coli Global Gene Expression in Urine from Women with Urinary Tract Infection

    PubMed Central

    Rasko, David A.; Faerber, Gary J.; Mobley, Harry L. T.

    2010-01-01

    Murine models of urinary tract infection (UTI) have provided substantial data identifying uropathogenic E. coli (UPEC) virulence factors and assessing their expression in vivo. However, it is unclear how gene expression in these animal models compares to UPEC gene expression during UTI in humans. To address this, we used a UPEC strain CFT073-specific microarray to measure global gene expression in eight E. coli isolates monitored directly from the urine of eight women presenting at a clinic with bacteriuria. The resulting gene expression profiles were compared to those of the same E. coli isolates cultured statically to exponential phase in pooled, sterilized human urine ex vivo. Known fitness factors, including iron acquisition and peptide transport systems, were highly expressed during human UTI and support a model in which UPEC replicates rapidly in vivo. While these findings were often consistent with previous data obtained from the murine UTI model, host-specific differences were observed. Most strikingly, expression of type 1 fimbrial genes, which are among the most highly expressed genes during murine experimental UTI and encode an essential virulence factor for this experimental model, was undetectable in six of the eight E. coli strains from women with UTI. Despite the lack of type 1 fimbrial expression in the urine samples, these E. coli isolates were generally capable of expressing type 1 fimbriae in vitro and highly upregulated fimA upon experimental murine infection. The findings presented here provide insight into the metabolic and pathogenic profile of UPEC in urine from women with UTI and represent the first transcriptome analysis for any pathogenic E. coli during a naturally occurring infection in humans. PMID:21085611

  7. Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride.

    PubMed

    Salgado-Bustamante, Mariana; Ortiz-Pérez, María D; Calderón-Aranda, Emma; Estrada-Capetillo, Lizbeth; Niño-Moreno, Perla; González-Amaro, Roberto; Portales-Pérez, Diana

    2010-01-15

    We have assessed whether the combined exposure to arsenic (As) and fluoride (F) exerts a different effect than the exposure to As alone on the pattern of expression of apoptosis and inflammatory genes by immune cells. RNA was extracted from peripheral blood mononuclear cells from twenty individuals exposed or not to As or F or both. Then, cDNA was isolated, and the expression of 180 genes related to apoptosis and inflammation was tested by a cDNA array test. We found significant differences in the expression of 9 apoptosis and 15 inflammation genes in the three exposed groups compared to non-exposed individuals. In addition, subjects exposed to As or F or both showed different patterns of expression of at least 19 genes. Our data indicate that the combined exposure to As and F has a different effect on gene expression than the exposure to As or F alone.

  8. 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...

  9. 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.

  10. 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...

  11. A Distinct and Replicable Squamous Cell Carcinoma Gene INPPA5 Variant Modifies Susceptibility of Arsenic-Associated Skin Lesions in Bangladesh

    PubMed Central

    Seow, Wei Jie; Pan, Wen-Chi; Kile, Molly L.; Lin, Tong; Baccarelli, Andrea; Quamruzzaman, Quazi; Rahman, Mahmuder; Mostofa, Golam; Rakibuz-Zaman, Muhammad; Kibriya, Muhammad; Ahsan, Habibul; Lin, Xihong; Christiani, David C.

    2015-01-01

    Background Single nucleotide polymorphisms (SNPs) in inflammation, one-carbon metabolism and skin cancer genes might influence susceptibility to arsenic-induced skin lesions. Methods A case-control study was conducted in Pabna, Bangladesh (2001-2003) and drinking water arsenic concentration was measured for each participant. A panel of twenty-five candidate SNPs was analyzed in 540 cases and 400 controls. Logistic regression was used to estimate the association between each SNP and the potential for gene-environment interactions in skin lesion risk adjusting for relevant covariates. Replication testing was conducted in an independent Bangladesh population with 488 cases and 2,794 controls. Results In the discovery population, genetic variants in the one-carbon metabolism genes PEMT (rs2278952, P for interaction = 0.004; rs897453, P for interaction = 0.05) and DHFR (rs1650697, P for interaction = 0.02), inflammation gene IL10 (rs3024496, P for interaction = 0.04), and skin cancer genes INPP5A (rs1133400, P for interaction = 0.03) and XPC (rs2228000, P for interaction = 0.01) significantly modified the association between arsenic and skin lesions after adjusting for multiple comparisons. The significant gene-environment interaction between a SNP in INPP5A gene (rs1133400) and water arsenic on skin lesion risk was successfully replicated in an independent population (P for interaction = 0.03). Conclusion Minor allele carriers of skin cancer gene INPP5A modified odds of arsenic-induced skin lesions in both main and replicative populations. Genetic variation in INPP5A appears to have a role in susceptibility to arsenic toxicity. PMID:25759212

  12. Transplacental exposure to inorganic arsenic at a hepatocarcinogenic dose induces fetal gene expression changes in mice indicative of aberrant estrogen signaling and disrupted steroid metabolism

    SciTech Connect

    Liu Jie . E-mail: Liu6@niehs.nih.gov; Xie Yaxiong; Cooper, Ryan; Ducharme, Danica M.K.; Tennant, Raymond; Diwan, Bhalchandra A.; Waalkes, Michael P.

    2007-05-01

    Exposure to inorganic arsenic in utero in C3H mice produces hepatocellular carcinoma in male offspring when they reach adulthood. To help define the molecular events associated with the fetal onset of arsenic hepatocarcinogenesis, pregnant C3H mice were given drinking water containing 0 (control) or 85 ppm arsenic from day 8 to 18 of gestation. At the end of the arsenic exposure period, male fetal livers were removed and RNA isolated for microarray analysis using 22K oligo chips. Arsenic exposure in utero produced significant (p < 0.001) alterations in expression of 187 genes, with approximately 25% of aberrantly expressed genes related to either estrogen signaling or steroid metabolism. Real-time RT-PCR on selected genes confirmed these changes. Various genes controlled by estrogen, including X-inactive-specific transcript, anterior gradient-2, trefoil factor-1, CRP-ductin, ghrelin, and small proline-rich protein-2A, were dramatically over-expressed. Estrogen-regulated genes including cytokeratin 1-19 and Cyp2a4 were over-expressed, although Cyp3a25 was suppressed. Several genes involved with steroid metabolism also showed remarkable expression changes, including increased expression of 17{beta}-hydroxysteroid dehydrogenase-7 (HSD17{beta}7; involved in estradiol production) and decreased expression of HSD17{beta}5 (involved in testosterone production). The expression of key genes important in methionine metabolism, such as methionine adenosyltransferase-1a, betaine-homocysteine methyltransferase and thioether S-methyltransferase, were suppressed. Thus, exposure of mouse fetus to inorganic arsenic during a critical period in development significantly alters the expression of various genes encoding estrogen signaling and steroid or methionine metabolism. These alterations could disrupt genetic programming at the very early life stage, which could impact tumor formation much later in adulthood.

  13. Transplacental exposure to inorganic arsenic at a hepatocarcinogenic dose induces fetal gene expression changes in mice indicative of aberrant estrogen signaling and disrupted steroid metabolism.

    PubMed

    Liu, Jie; Xie, Yaxiong; Cooper, Ryan; Ducharme, Danica M K; Tennant, Raymond; Diwan, Bhalchandra A; Waalkes, Michael P

    2007-05-01

    Exposure to inorganic arsenic in utero in C3H mice produces hepatocellular carcinoma in male offspring when they reach adulthood. To help define the molecular events associated with the fetal onset of arsenic hepatocarcinogenesis, pregnant C3H mice were given drinking water containing 0 (control) or 85 ppm arsenic from day 8 to 18 of gestation. At the end of the arsenic exposure period, male fetal livers were removed and RNA isolated for microarray analysis using 22K oligo chips. Arsenic exposure in utero produced significant (p<0.001) alterations in expression of 187 genes, with approximately 25% of aberrantly expressed genes related to either estrogen signaling or steroid metabolism. Real-time RT-PCR on selected genes confirmed these changes. Various genes controlled by estrogen, including X-inactive-specific transcript, anterior gradient-2, trefoil factor-1, CRP-ductin, ghrelin, and small proline-rich protein-2A, were dramatically over-expressed. Estrogen-regulated genes including cytokeratin 1-19 and Cyp2a4 were over-expressed, although Cyp3a25 was suppressed. Several genes involved with steroid metabolism also showed remarkable expression changes, including increased expression of 17beta-hydroxysteroid dehydrogenase-7 (HSD17beta7; involved in estradiol production) and decreased expression of HSD17beta5 (involved in testosterone production). The expression of key genes important in methionine metabolism, such as methionine adenosyltransferase-1a, betaine-homocysteine methyltransferase and thioether S-methyltransferase, were suppressed. Thus, exposure of mouse fetus to inorganic arsenic during a critical period in development significantly alters the expression of various genes encoding estrogen signaling and steroid or methionine metabolism. These alterations could disrupt genetic programming at the very early life stage, which could impact tumor formation much later in adulthood.

  14. 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...

  15. 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...

  16. Further studies on aberrant gene expression associated with arsenic-induced malignant transformation in rat liver TRL1215 cells

    SciTech Connect

    Liu Jie . E-mail: Liu6@niehs.nih.gov; Benbrahim-Tallaa, Lamia; Qian Xun; Yu, Limei; Xie Yaxiong; Boos, Jennifer; Qu Wei; Waalkes, Michael P.

    2006-11-01

    Chronic arsenic exposure of rat liver epithelial TRL1215 cells induced malignant transformation in a concentration-dependent manner. To further define the molecular events of these arsenic-transformed cells (termed CAsE cells), gene expressions associated with arsenic carcinogenesis or influenced by methylation were examined. Real-time RT-PCR showed that at carcinogenic concentrations (500 nM, and to a less extent 250 nM of arsenite), the expressions of {alpha}-fetoprotein (AFP), Wilm's tumor protein-1 (WT-1), c-jun, c-myc, H-ras, c-met and hepatocyte growth factor, heme oxygenase-1, superoxide dismutase-1, glutathione-S-transferase-{pi} and metallothionein-1 (MT) were increased between 3 to 12-fold, while expressions of insulin-like growth factor II (IGF-II) and fibroblast growth factor receptor (FGFR1) were essentially abolished. These changes were not significant at the non-carcinogenic concentration (125 nM), except for IGF-II. The positive cell-cycle regulators cyclin D1 and PCNA were overexpressed in CAsE cells, while the negative regulators p21 and p16 were suppressed. Western-blot confirmed increases in AFP, WT-1, cyclin D1 and decreases in p16 and p21 protein in CAsE cells. The CAsE cells over-expressed MT but the demethylating agent 5-aza-deoxycytidine (5-aza-dC, 2.5 {mu}M, 72 h) stimulated further MT expression. 5-Aza-deoxycytidine restored the loss of expression of p21 in CAsE cells to control levels, but did not restore the expression of p16, IGF-II, or FGFR1, indicating the loss of expression of these genes is due to factors other than DNA methylation changes. Overall, an intricate variety of gene expression changes occur in arsenic-induced malignant transformation of liver cells including oncogene activation and alterations in expression of genes critical to growth regulation.

  17. Metabolic profile in workers occupationally exposed to arsenic: role of GST polymorphisms.

    PubMed

    Marcos, Ricardo; Martínez, Valeria; Hernández, Alba; Creus, Amadeu; Sekaran, Chandra; Tokunaga, Hiroshi; Quinteros, Domingo

    2006-03-01

    Arsenic is a well-known human carcinogen with a ubiquitous distribution in the natural environment. Chronic exposure to inorganic arsenic involves a biotransformation process that leds to the main excretion of organic methylated metabolites, such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as well as the parental inorganic species. Interindividual variation in arsenic metabolism has been extensively reported, and polymorphisms in genes involved in such process could be related to changes in the arsenic excretion profile and the response to chronic exposures. Our analysis of the metabolic profiles in three groups of workers exposed to different arsenic exposure levels showed high amounts of inorganic arsenic and MMA in the most-exposed workers versus the least-exposed workers, in whom high amounts of DMA were observed. With respect to the role of different genetic polymorphisms in the glutathione S-transferase (GST) genes in the modulation of the urinary profiles, for the overall population only a tendency was just observed between GSTM1 null and MMA excretion as well as between GSTP1 val/val and DMA excretion.

  18. Effects of arsenic exposure from drinking water on spatial memory, ultra-structures and NMDAR gene expression of hippocampus in rats.

    PubMed

    Luo, Jiao-hua; Qiu, Zhi-qun; Shu, Wei-qun; Zhang, Yong-yan; Zhang, Liang; Chen, Ji-an

    2009-01-30

    Epidemiological investigations indicate that chronic arsenic exposure can damage neurobehavioral function in children. The present study was aimed to study the effects of arsenic exposure from drinking water on the spatial memory, and hippocampal ultra-structures and N-methyl-d-aspartate receptor (NMDAR) gene expression in rats. Sprague-Dawley rats were assigned to four groups: rats in control group drank regular water, rats in other groups drank water with final arsenic concentration of 2.72 mg/L (group A), 13.6 mg/L (group B) and 68 mg/L (group C), respectively, for 3 months. The levels of arsenic in blood serum and hippocampus were monitored. Rats were tested in Morris water maze (MWM) for memory status. Samples of hippocampus were collected from two rats in each group for transmission electron microscopic study and the detection of NMDAR expression by RT-PCR. The rats in group C showed a significant delay in hidden platform acquisition. Neurons and endothelial cells presented pathological changes and the expression of NR2A was down-regulated in hippocampus in arsenic exposed rats. Our data indicated that arsenic exposure of 68 mg/L caused spatial memory damage, of which the morphological and biochemical bases could be the ultra-structure changes and reduced NR2A expression in hippocampus.

  19. Characterization of gene expression changes associated with MNNG, arsenic, or metal mixture treatment in human keratinocytes: application of cDNA microarray technology.

    PubMed Central

    Bae, Dong-Soon; Hanneman, William H; Yang, Raymond S H; Campain, Julie A

    2002-01-01

    The identification of molecular markers related to critical biological processes during carcinogenesis may aid in the evaluation of carcinogenic potentials of chemicals and chemical mixtures. Work from our laboratory demonstrated that a single treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) enhanced spontaneous malignant transformation of the human keratinocyte cell line RHEK-1. In contrast, chronic low-level exposure of cells to arsenic alone or in a mixture containing arsenic, cadmium, chromium, and lead inhibited malignant conversion. To identify changes in gene expression that influence these different outcomes, cDNA microarray technology was used. Analysis of multiple human arrays in MNNG-transformed RHEK-1 cells, designated OM3, and those treated with arsenic or the arsenic-containing metal mixture showed unique patterns of gene expression. Genes that were overexpressed in OM3 included oncogenes, cell cycle regulators, and those involved in signal transduction, whereas genes for DNA repair enzymes and inhibitors of transformation and metastasis were suppressed. In arsenic-treated cells, multiple DNA repair proteins were overexpressed. Mixture-treated cells showed increased expression of a variety of genes including metallothioneins and integrin 4. These cells showed decreased expression of oncogenes, DNA repair proteins, and genes involved in the mitogen-activated protein kinase pathway. For comparison we are currently analyzing gene expression changes in RHEK-1 cells transformed by other means. The goal of these studies is to identify common batteries of genes affected by chemical modulators of the carcinogenic process. Mechanistic studies may allow us to correlate alterations in their expression with sequential stages in the carcinogenic process and may aid in the risk assessment of other xenobiotics. PMID:12634122

  20. Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain

    PubMed Central

    Goins, WF; Goss, JR; Chancellor, MB; de Groat, WC; Glorioso, JC; Yoshimura, N

    2009-01-01

    Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a painful debilitating chronic visceral pain disorder of unknown etiology that affects an estimated 1 million people in the, United States alone. It is characterized by inflammation of the bladder that results in chronic pelvic pain associated with bladder symptoms of urinary frequency and urgency. Regardless of the etiology, IC/PBS involves either increased and/or abnormal activity in afferent nociceptive sensory neurons. Pain-related symptoms in patients with IC/PBS are often very difficult to treat. Both medical and surgical therapies have had limited clinical utility in this debilitating disease and numerous drug treatments, such as heparin, dimethylsulfoxide and amitriptyline, have proven to be palliative at best, and in some IC/PBS patients provide no relief whatsoever. Although opiate narcotics have been employed to help alleviate IC/PBS pain, this strategy is fraught with problems as systemic narcotic administration causes multiple unwanted side effects including mental status change and constipation. Moreover, chronic systemic narcotic use leads to dependency and need for dose escalation due to tolerance: therefore, new therapies are desperately needed to treat refractory IC/PBS. This has led our group to develop a gene therapy strategy that could potentially alleviate chronic pelvic pain using the herpes simplex virus-directed delivery of analgesic proteins to the bladder. PMID:19242523

  1. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24721130

  3. Hydrogen peroxide triggers a novel alternative splicing of arsenic (+3 oxidation state) methyltransferase gene.

    PubMed

    Sumi, Daigo; Takeda, Chieri; Yasuoka, Daiki; Himeno, Seiichiro

    2016-11-04

    We previously reported that two splicing variants of human AS3MT mRNA, exon-3 skipping form (Δ3) and exons-4 and -5 skipping form (Δ4,5), were detected in HepG2 cells and that both variants lacked arsenic methylation activity (Sumi et al., 2011). Here we studied whether hydrogen peroxide (H2O2) triggers alternative splicing of AS3MT mRNA. The results showed that exposure of HepG2 cells to H2O2 resulted in increased levels of a novel spliced form skipping exon-3 to exon-10 (Δ3-10) in an H2O2-concentration-dependent manner, although no change was detected in the mRNA levels of Δ3 AS3MT. We found decreased protein levels of serine/arginine-rich 40 (SRp40), which we determined to be a candidate splice factor for controlling the splicing of AS3MT mRNA. We next compared the amounts of methylated arsenic metabolites between control and H2O2-exposed HepG2 cells after the addition of arsenite as a substance. The results showed lower levels of methylated arsenic metabolites in HepG2 cells exposed to H2O2. These data suggest that the splicing of AS3MT pre-mRNA was disconcerted by oxidative stress and that abnormal alternative splicing of AS3MT mRNA may affect arsenic methylation ability.

  4. Identification of genes and physiological factors that reduce accumulation of arsenic in rice grain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The arsenic (As) levels in rice grains and food products can reach toxic levels when produced under certain growing conditions. The World Health Organization (WHO) recently set a CODEX limit of 0.2 ppm inorganic As in milled white rice, and lower limits may be set for baby food products. While studi...

  5. Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

    PubMed

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

    2012-01-01

    Arsenic contamination of drinking water is a major public health issue in many countries, increasing risk for a wide array of diseases, including cancer. There is inter-individual variation in arsenic metabolism efficiency and susceptibility to arsenic toxicity; however, the basis of this variation is not well understood. Here, we have performed the first genome-wide association study (GWAS) of arsenic-related metabolism and toxicity phenotypes to improve our understanding of the mechanisms by which arsenic affects health. Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs) for 1,313 arsenic-exposed Bangladeshi individuals, we identified genome-wide significant association signals (P<5×10(-8)) for percentages of both monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) near the AS3MT gene (arsenite methyltransferase; 10q24.32), with five genetic variants showing independent associations. In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity) and 1,794 controls, we show that one of these five variants (rs9527) is also associated with skin lesion risk (P = 0.0005). Using a subset of individuals with prospectively measured arsenic (n = 769), we show that rs9527 interacts with arsenic to influence incident skin lesion risk (P = 0.01). Expression quantitative trait locus (eQTL) analyses of genome-wide expression data from 950 individual's lymphocyte RNA suggest that several of our lead SNPs represent cis-eQTLs for AS3MT (P = 10(-12)) and neighboring gene C10orf32 (P = 10(-44)), which are involved in C10orf32-AS3MT read-through transcription. This is the largest and most comprehensive genomic investigation of arsenic metabolism and toxicity to date, the only GWAS of any arsenic-related trait, and the first study to implicate 10q24.32 variants in both arsenic metabolism and arsenical skin

  6. Efficient arsenic metabolism--the AS3MT haplotype is associated with DNA methylation and expression of multiple genes around AS3MT.

    PubMed

    Engström, Karin S; Hossain, Mohammad Bakhtiar; Lauss, Martin; Ahmed, Sultan; Raqib, Rubhana; Vahter, Marie; Broberg, Karin

    2013-01-01

    Arsenic is a very potent toxicant. One major susceptibility factor for arsenic-related toxicity is the efficiency of arsenic metabolism. The efficiency, in turn, is associated with non-coding single nucleotide polymorphisms (SNPs) in the arsenic methyltransferase AS3MT on chromosome 10q24. However, the mechanism of action for these SNPs is not yet clarified. Here, we assessed the influence of genetic variation in AS3MT on DNA methylation and gene expression within 10q24, in people exposed to arsenic in drinking water. DNA was extracted from peripheral blood from women in the Argentinean Andes (N = 103) and from cord blood from new-borns in Bangladesh (N = 127). AS3MT SNPs were analyzed with Sequenom or Taqman assays. Whole genome epigenetic analysis with Infinium HumanMethylation450 BeadChip was performed on bisulphite-treated DNA. Whole genome gene expression analysis was performed with Illumina DirectHyb HumanHT-12 v4.0 on RNA from peripheral blood. Arsenic exposure was assessed by HPLC-ICPMS. In the Argentinean women, the major AS3MT haplotype, associated with more efficient arsenic metabolism, showed increased methylation of AS3MT (p = 10(-6)) and also differential methylation of several other genes within about 800 kilobasepairs: CNNM2 (p<10(-16)), NT5C2 (p<10(-16)), C10orf26 (p = 10(-8)), USMG5 (p = 10(-5)), TRIM8 (p = 10(-4)), and CALHM2 (p = 0.038) (adjusted for multiple comparisons). Similar, but weaker, associations between AS3MT haplotype and DNA methylation in 10q24 were observed in cord blood (Bangladesh). The haplotype-associated altered CpG methylation was correlated with reduced expression of AS3MT and CNNM2 (r(s) = -0.22 to -0.54), and with increased expression of NT5C2 and USMG5 (r(s) = 0.25 to 0.58). Taking other possibly influential variables into account in multivariable linear models did only to a minor extent alter the strength of the associations. In conclusion, the AS3MT haplotype status strongly

  7. Association of urinary bladder paragangliomas with germline mutations in the SDHB and VHL genes

    PubMed Central

    Martucci, Victoria L.; Lorenzo, Zarina G.; Weintraub, Michael; del Rivero, Jaydira; Ling, Alexander; Merino, Maria; Siddiqui, Minhaj; Shuch, Brian; Vourganti, Srinivas; Linehan, W. Marston; Agarwal, Piyush K.; Pacak, Karel

    2015-01-01

    Objective Our primary goal was to examine the clinical characteristics of a series of patients with urinary bladder paragangliomas (UBPGLs), focusing particularly on their genetic backgrounds. Materials and methods We analyzed the medical records of patients who presented to the National Institutes of Health with UBPGL from 2000 to 2013 to determine their clinical characteristics and outcomes, biochemical phenotype, tumor size, and genetic background. Results Of the 27 patients with UBPGLs who were identified, 17 (63%) had underlying genetic mutations. Overall, 14 (51.9%) patients had a germline mutation in the succinate dehydrogenase subunit B gene (SDHB), and 3 (11.1%) had in the von Hippel-Lindau gene (VHL). Of the 21 patients who had biochemical data available before their first operation, 19 (90.5%) presented with a noradrenergic biochemical phenotype; 7 (33.3%) patients had tumors that also secreted dopamine. In addition, 1 patient (4.8%) had elevated metanephrine levels, and 2 (9.5%) had normal biochemical data. In total, 13 (48.1%) patients in the series were diagnosed with metastatic disease, at either first presentation or follow-up; 6 of these patients (46.1%) had SDHB mutations. Conclusions UBPGLs typically present with a noradrenergic phenotype and are frequently associated with underlying germline mutations. Patients presenting with these rare neuroendocrine tumors should be screened for these mutations. In addition, patients with UBPGLs should be followed up closely for metastatic development regardless of genetic background, as almost half of the patients in this series presented with metastatic disease and less than half of them had SDHB mutations. PMID:25683602

  8. Quantification of DNA in urinary porcine bladder matrix using the ACTB gene.

    PubMed

    Silva-Benítez, Erika; Soto-Sáinz, Eduardo; Pozos-Guillen, Amaury; Romero-Quintana, José Geovanni; Aguilar-Medina, Maribel; Ayala-Ham, Alfredo; Peña-Martínez, Eri; Ramos-Payán, Rosalío; Flores, Héctor

    2015-11-01

    Extracellular matrix (ECM) is a rich network of proteins and proteoglycans that has proved to be very useful in tissue regeneration. Porcine ECM has been proposed as a biological scaffold, and urinary bladder matrix (UBM) has demonstrated superior biological properties; however, its use in human treatment requires ensuring that it is DNA free. Several protocols have been used for decellularization and to demonstrate the absence of DNA, but until now, a porcine housekeeping gene for quantifying DNA by real-time quantitative PCR (qPCR) has been limiting. The aim of this study was to propose a protocol to quantify the DNA content of decellularized UBM by qPCR for the beta-actin gene (ACTB). A total of 20 porcine bladders were used, and each bladder was divided into three pieces: one as a control and the others decellularized with either SDS or Triton X-100 detergent. The presence of DNA was assessed by histology, spectrophotometry, conventional PCR, and qPCR for the ACTB. Histological analysis demonstrated the absence of nuclei using both protocols. Spectrophotometrical evaluation resulted in DNA concentrations of 1561.4 ± 357.1 and 1211.9 ± 635.2 ng of DNA/mg dry weight after the SDS and Triton X-100 protocols, respectively. DNA was not detected in any protocol by conventional PCR. In contrast, using qPCR, we found 3.9 ± 2.8 ng of DNA/mg dry weight in the Triton X-100 protocol. Therefore, the use of qPCR is a reliable method to quantify residual DNA content after decellularization procedures.

  9. 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...

  10. 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...

  11. ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development.

    PubMed

    Zhang, Rong; Knapp, Michael; Suzuki, Kentaro; Kajioka, Daiki; Schmidt, Johanna M; Winkler, Jonas; Yilmaz, Öznur; Pleschka, Michael; Cao, Jia; Kockum, Christina Clementson; Barker, Gillian; Holmdahl, Gundela; Beaman, Glenda; Keene, David; Woolf, Adrian S; Cervellione, Raimondo M; Cheng, Wei; Wilkins, Simon; Gearhart, John P; Sirchia, Fabio; Di Grazia, Massimo; Ebert, Anne-Karolin; Rösch, Wolfgang; Ellinger, Jörg; Jenetzky, Ekkehart; Zwink, Nadine; Feitz, Wout F; Marcelis, Carlo; Schumacher, Johannes; Martinón-Torres, Federico; Hibberd, Martin Lloyd; Khor, Chiea Chuen; Heilmann-Heimbach, Stefanie; Barth, Sandra; Boyadjiev, Simeon A; Brusco, Alfredo; Ludwig, Michael; Newman, William; Nordenskjöld, Agneta; Yamada, Gen; Odermatt, Benjamin; Reutter, Heiko

    2017-02-08

    Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 × 10(-08)). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 × 10(-19). Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.

  12. ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development

    PubMed Central

    Zhang, Rong; Knapp, Michael; Suzuki, Kentaro; Kajioka, Daiki; Schmidt, Johanna M.; Winkler, Jonas; Yilmaz, Öznur; Pleschka, Michael; Cao, Jia; Kockum, Christina Clementson; Barker, Gillian; Holmdahl, Gundela; Beaman, Glenda; Keene, David; Woolf, Adrian S.; Cervellione, Raimondo M.; Cheng, Wei; Wilkins, Simon; Gearhart, John P.; Sirchia, Fabio; Di Grazia, Massimo; Ebert, Anne-Karolin; Rösch, Wolfgang; Ellinger, Jörg; Jenetzky, Ekkehart; Zwink, Nadine; Feitz, Wout F.; Marcelis, Carlo; Schumacher, Johannes; Martinón-Torres, Federico; Hibberd, Martin Lloyd; Khor, Chiea Chuen; Heilmann-Heimbach, Stefanie; Barth, Sandra; Boyadjiev, Simeon A.; Brusco, Alfredo; Ludwig, Michael; Newman, William; Nordenskjöld, Agneta; Yamada, Gen; Odermatt, Benjamin; Reutter, Heiko

    2017-01-01

    Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 × 10−08). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 × 10−19. Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development. PMID:28176844

  13. 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...

  14. [Lower urinary tract dysfunction and neuropathological findings of the neural circuits controlling micturition in familial amyotrophic lateral sclerosis with L106V mutation in the SOD1 gene].

    PubMed

    Hineno, Akiyo; Oyanagi, Kiyomitsu; Nakamura, Akinori; Shimojima, Yoshio; Yoshida, Kunihiro; Ikeda, Shu-Ichi

    2016-01-01

    We report lower urinary tract dysfunction and neuropathological findings of the neural circuits controlling micturition in the patients with familial amyotrophic lateral sclerosis having L106V mutation in the SOD1 gene. Ten of 20 patients showed lower urinary tract dysfunction and 5 patients developed within 1 year after the onset of weakness. In 8 patients with an artificial respirator, 6 patients showed lower urinary tract dysfunction. Lower urinary tract dysfunction and respiratory failure requiring an artificial respirator occurred simultaneously in 3 patients. Neuronal loss and gliosis were observed in the neural circuits controlling micturition, such as frontal lobe, thalamus, hypothalamus, striatum, periaqueductal gray, ascending spinal tract, lateral corticospinal tract, intermediolateral nucleus and Onufrowicz' nucleus. Lower urinary tract dysfunction, especially storage symptoms, developed about 1 year after the onset of weakness, and the dysfunction occurred simultaneously with artificial respirator use in the patients.

  15. Transformation and characterization of an arsenic gene operon from urease-positive thermophilic Campylobacter (UPTC) in Escherichia coli.

    PubMed

    Matsuda, M; Kuribayashi, T; Yamamoto, S; Millar, B C; Moore, J E

    2016-01-01

    An arsenate susceptibility test was performed with transformed and cultured Escherichia coli DH5α cells, which carried recombinant DNA of full-length arsenic (ars) operon, namely a putative membrane permease, ArsP; a transcriptional repressor, ArsR; an arsenate reductase, ArsC; and an arsenical-resistance membrane transporter, Acr3, from the Japanese urease-positive thermophilic Campylobacter lari (UPTC) CF89-12. The E. coli DH5α transformant showed reduced susceptibility to arsenate (~1536 μg/mL), compared to the control. Thus, these ars four-genes from the UPTC CF89-12 strain cells could confer a reduced susceptibility to arsenate in the transformed and E. coli DH5α cells. E. coli transformants with truncated ars operons, acr3 (acr3) and arsC-acr3 (∆arsC-acr3), of the ars operon, showed an MIC value of 384 μg/mL (~384 μg/mL), similar to the E. coli cells which carried the pGEM-T vector (control). Reverse transcription PCR confirmed in vivo transcription of recombinant full-length ars operon and deletion variants (∆acr3 and ∆arsC-acr3) in the transformed E. coli cells.

  16. Arsenic and bladder cancer: observations and suggestions.

    PubMed

    Radosavljević, Vladan; Jakovljević, Branko

    2008-10-01

    Arsenic from drinking water is a well-known risk factor for bladder cancer. The purpose of this paper is to systematize some important yet often overlooked facts considering the relationship between arsenic exposure and the occurrence of bladder cancer. Since the exposure to inorganic arsenic from food, inhaled air, and skin absorption as well as arsenic methylation ability are not fully investigated, our assumption is that the exposure of arsenic only from drinking water is underestimated and its role as a risk factor is highly overestimated. This paper proposes some qualitative and quantitative parameters of arsenic as a risk factor for bladder cancer. The recommended qualitative parameters of arsenic intake are first, pathways of exposure, and second, toxicity and metabolism. The suggested quantitative parameters of arsenic intake include amounts of arsenic absorbed in the body, duration of arsenic exposure, and duration of arsenic presence in the urinary bladder. This approach can be implemented in a systematic classification and explanation of various risk factors and their mutual interactions for other types of cancer or diseases in general.

  17. Arsenic Methylation and its Relationship to Abundance and Diversity of arsM Genes in Composting Manure

    PubMed Central

    Zhai, Weiwei; Wong, Mabel T.; Luo, Fei; Hashmi, Muhammad Z.; Liu, Xingmei; Edwards, Elizabeth A.; Tang, Xianjin; Xu, Jianming

    2017-01-01

    Although methylation is regarded as one of the main detoxification pathways for arsenic (As), current knowledge about this process during manure composting remains limited. In this study, two pilot-scale compost piles were established to treat manure contaminated with As. An overall accumulation of methylated As occurred during 60 day-composting time. The concentration of monomethylarsonic acid (MMA) increased from 6 to 190 μg kg−1 within 15 days and decreased to 35 μg kg−1 at the end of the maturing phase; while the concentration of dimethylarsinic acid (DMA) continuously increased from 33 to 595 μg kg−1 over the composting time. The arsM gene copies increased gradually from 0.08 × 109 to 6.82 × 109 copies g−1 dry mass over time and correlated positively to the concentrations of methylated As. 16S rRNA gene sequencing and arsM clone library analysis confirmed the high abundance and diversity of arsM genes. Many of these genes were related to those from known As-methylating microbes, including Streptomyces sp., Amycolatopsis mediterranei and Sphaerobacter thermophiles. These results demonstrated that As methylation during manure composting is significant and, for the first time, established a linkage between As biomethylation and the abundance and diversity of the arsM functional genes in composting manure. PMID:28266584

  18. Arsenic Methylation and its Relationship to Abundance and Diversity of arsM Genes in Composting Manure

    NASA Astrophysics Data System (ADS)

    Zhai, Weiwei; Wong, Mabel T.; Luo, Fei; Hashmi, Muhammad Z.; Liu, Xingmei; Edwards, Elizabeth A.; Tang, Xianjin; Xu, Jianming

    2017-03-01

    Although methylation is regarded as one of the main detoxification pathways for arsenic (As), current knowledge about this process during manure composting remains limited. In this study, two pilot-scale compost piles were established to treat manure contaminated with As. An overall accumulation of methylated As occurred during 60 day-composting time. The concentration of monomethylarsonic acid (MMA) increased from 6 to 190 μg kg‑1 within 15 days and decreased to 35 μg kg‑1 at the end of the maturing phase; while the concentration of dimethylarsinic acid (DMA) continuously increased from 33 to 595 μg kg‑1 over the composting time. The arsM gene copies increased gradually from 0.08 × 109 to 6.82 × 109 copies g‑1 dry mass over time and correlated positively to the concentrations of methylated As. 16S rRNA gene sequencing and arsM clone library analysis confirmed the high abundance and diversity of arsM genes. Many of these genes were related to those from known As-methylating microbes, including Streptomyces sp., Amycolatopsis mediterranei and Sphaerobacter thermophiles. These results demonstrated that As methylation during manure composting is significant and, for the first time, established a linkage between As biomethylation and the abundance and diversity of the arsM functional genes in composting manure.

  19. Arsenic Methyltransferase

    EPA Science Inventory

    The metalloid arsenic enters the environment by natural processes (volcanic activity, weathering of rocks) and by human activity (mining, smelting, herbicides and pesticides). Although arsenic has been exploited for homicidal and suicidal purposes since antiquity, its significan...

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

    SciTech Connect

    Chiang, Chien-I; Huang, Ya-Li; Chen, Wei-Jen; Shiue, Horng-Sheng; Huang, Chao-Yuan; Pu, Yeong-Shiau; Lin, Ying-Chin; Hsueh, Yu-Mei

    2014-09-15

    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 Lys751Gln 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

  1. Gene expression profiling analysis reveals arsenic-induced cell cycle arrest and apoptosis in p53-proficient and p53-deficient cells through differential gene pathways

    SciTech Connect

    Yu Xiaozhong Robinson, Joshua F.; Gribble, Elizabeth; Hong, Sung Woo; Sidhu, Jaspreet S.; Faustman, Elaine M.

    2008-12-15

    Arsenic (As) is a well-known environmental toxicant and carcinogen as well as an effective chemotherapeutic agent. The underlying mechanism of this dual capability, however, is not fully understood. Tumor suppressor gene p53, a pivotal cell cycle checkpoint signaling protein, has been hypothesized to play a possible role in mediating As-induced toxicity and therapeutic efficiency. In this study, we found that arsenite (As{sup 3+}) induced apoptosis and cell cycle arrest in a dose-dependent manner in both p53{sup +/+} and p53{sup -/-} mouse embryonic fibroblasts (MEFs). There was, however, a distinction between genotypes in the apoptotic response, with a more prominent induction of caspase-3 in the p53{sup -/-} cells than in the p53{sup +/+} cells. To examine this difference further, a systems-based genomic analysis was conducted comparing the critical molecular mechanisms between the p53 genotypes in response to As{sup 3+}. A significant alteration in the Nrf2-mediated oxidative stress response pathway was found in both genotypes. In p53{sup +/+} MEFs, As{sup 3+} induced p53-dependent gene expression alterations in DNA damage and cell cycle regulation genes. However, in the p53{sup -/-} MEFs, As{sup 3+} induced a significant up-regulation of pro-apoptotic genes (Noxa) and down-regulation of genes in immune modulation. Our findings demonstrate that As-induced cell death occurs through a p53-independent pathway in p53 deficient cells while apoptosis induction occurs through p53-dependent pathway in normal tissue. This difference in the mechanism of apoptotic responses between the genotypes provides important information regarding the apparent dichotomy of arsenic's dual mechanisms, and potentially leads to further advancement of its utility as a chemotherapeutic agent.

  2. Differential DNA methylation profile of key genes in malignant prostate epithelial cells transformed by inorganic arsenic or cadmium

    SciTech Connect

    Pelch, Katherine E.; Tokar, Erik J.; Merrick, B. Alex; Waalkes, Michael P.

    2015-08-01

    Previous work shows altered methylation patterns in inorganic arsenic (iAs)- or cadmium (Cd)-transformed epithelial cells. Here, the methylation status near the transcriptional start site was assessed in the normal human prostate epithelial cell line (RWPE-1) that was malignantly transformed by 10 μM Cd for 11 weeks (CTPE) or 5 μM iAs for 29 weeks (CAsE-PE), at which time cells showed multiple markers of acquired cancer phenotype. Next generation sequencing of the transcriptome of CAsE-PE cells identified multiple dysregulated genes. Of the most highly dysregulated genes, five genes that can be relevant to the carcinogenic process (S100P, HYAL1, NTM, NES, ALDH1A1) were chosen for an in-depth analysis of the DNA methylation profile. DNA was isolated, bisulfite converted, and combined bisulfite restriction analysis was used to identify differentially methylated CpG sites, which was confirmed with bisulfite sequencing. Four of the five genes showed differential methylation in transformants relative to control cells that was inversely related to altered gene expression. Increased expression of HYAL1 (> 25-fold) and S100P (> 40-fold) in transformants was correlated with hypomethylation near the transcriptional start site. Decreased expression of NES (> 15-fold) and NTM (> 1000-fold) in transformants was correlated with hypermethylation near the transcriptional start site. ALDH1A1 expression was differentially expressed in transformed cells but was not differentially methylated relative to control. In conclusion, altered gene expression observed in Cd and iAs transformed cells may result from altered DNA methylation status. - Highlights: • Cd and iAs are known human carcinogens, yet neither appears directly mutagenic. • Prior data suggest epigenetic modification plays a role in Cd or iAs induced cancer. • Altered methylation of four misregulated genes was found in Cd or iAs transformants. • The resulting altered gene expression may be relevant to cellular

  3. 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.

  4. Arsenic resistance genes of As-resistant purple nonsulfur bacteria isolated from As-contaminated sites for bioremediation application.

    PubMed

    Nookongbut, Phitthaya; Kantachote, Duangporn; Krishnan, Kannan; Megharaj, Mallavarapu

    2017-04-01

    This study aimed to identify arsenic resistant mechanisms in As-resistant purple nonsulfur bacteria (PNSB) by screening them for presence of As-resistance genes and related enzymes. Resistance to As(III) and As(V) of four As-resistant PNSB determined in terms of median inhibition concentration (IC50 values) were in the order of strains Rhodopseudomonas palustris C1 > R. palustris AB3 > Rubrivivax benzoatilyticus C31 > R. palustris L28 which corresponded to the presence of As-resistance genes in these bacteria. The strain C1 showed all As-marker genes; arsC, arsM, aioA, and acr3, while aioA was not detected in strain AB3. Strains C31 and L28 had only Arsenite-transporter gene, acr3. Translation of all these detected gene sequences of strain C1 to amino acid sequences showed that these proteins have vicinal cysteine; Cys126, Cys105, and Cys178 of Acr3, ArsC, AioA, respectively. Tertiary structure of proteins Acr3, ArsC, AioA, and ArsM showed strain C1 exhibits the high activities of arsenite oxidase and arsenate reductase enzymes that are encoded by aioA and arsC genes, respectively. Moreover, strain C1 with arsM gene produced volatile-methylated As-compounds; monomethylarsonic acid (MMA), dimethylarsenic acid (DMA), and arsenobetaine (AsB) in the presence of either As(III) or As(V). In conclusion, the strain C1 has great potential for its application in bioremediation of As-contaminated sites.

  5. 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

  6. In Vivo Effect of Arsenic Trioxide on Keap1-p62-Nrf2 Signaling Pathway in Mouse Liver: Expression of Antioxidant Responsive Element-Driven Genes Related to Glutathione Metabolism

    PubMed Central

    Srivastava, Ritu; Sengupta, Archya; Mukherjee, Sandip; Chatterjee, Sarmishtha; Sudarshan, Muthammal; Chakraborty, Anindita; Bhattacharya, Shelley; Chattopadhyay, Ansuman

    2013-01-01

    Arsenic is a Group I human carcinogen, and chronic arsenic exposure through drinking water is a major threat to human population. Liver is one of the major organs for the detoxification of arsenic. The present study was carried out in mice in vivo after arsenic treatment through drinking water at different doses and time of exposure. Arsenic toxicity is found to be mediated by reactive oxygen species. Nuclear factor (erythroid-2 related) factor 2 (Nrf2)/Keap1 (Kelch-like ECH-associated protein 1)/ARE (antioxidant response element)—driven target gene system protects cells against oxidative stress and maintains cellular oxidative homeostasis. Our result showed 0.4 ppm, 2 ppm, and 4 ppm arsenic trioxide treatment through drinking water for 30 days and 90 days induced damages in the liver of Swiss albino mice as evidenced by histopathology, disturbances in liver function, induction of heat shock protein 70, modulation of trace elements, alteration in reduced glutathione level, glutathione-s-transferase and catalase activity, malondialdehyde production, and induction of apoptosis. Cellular Nrf2 protein level and mRNA level increased in all treatment groups. Keap1 protein as well as mRNA level decreased concomitantly in arsenic treated mice. Our study clearly indicates the important role of Nrf2 in activating ARE driven genes related to GSH metabolic pathway and also the adaptive response mechanisms in arsenic induced hepatotoxicity. PMID:27335833

  7. In Vivo Effect of Arsenic Trioxide on Keap1-p62-Nrf2 Signaling Pathway in Mouse Liver: Expression of Antioxidant Responsive Element-Driven Genes Related to Glutathione Metabolism.

    PubMed

    Srivastava, Ritu; Sengupta, Archya; Mukherjee, Sandip; Chatterjee, Sarmishtha; Sudarshan, Muthammal; Chakraborty, Anindita; Bhattacharya, Shelley; Chattopadhyay, Ansuman

    2013-01-01

    Arsenic is a Group I human carcinogen, and chronic arsenic exposure through drinking water is a major threat to human population. Liver is one of the major organs for the detoxification of arsenic. The present study was carried out in mice in vivo after arsenic treatment through drinking water at different doses and time of exposure. Arsenic toxicity is found to be mediated by reactive oxygen species. Nuclear factor (erythroid-2 related) factor 2 (Nrf2)/Keap1 (Kelch-like ECH-associated protein 1)/ARE (antioxidant response element)-driven target gene system protects cells against oxidative stress and maintains cellular oxidative homeostasis. Our result showed 0.4 ppm, 2 ppm, and 4 ppm arsenic trioxide treatment through drinking water for 30 days and 90 days induced damages in the liver of Swiss albino mice as evidenced by histopathology, disturbances in liver function, induction of heat shock protein 70, modulation of trace elements, alteration in reduced glutathione level, glutathione-s-transferase and catalase activity, malondialdehyde production, and induction of apoptosis. Cellular Nrf2 protein level and mRNA level increased in all treatment groups. Keap1 protein as well as mRNA level decreased concomitantly in arsenic treated mice. Our study clearly indicates the important role of Nrf2 in activating ARE driven genes related to GSH metabolic pathway and also the adaptive response mechanisms in arsenic induced hepatotoxicity.

  8. Assessing arsenic exposure in households using bottled water or point-of-use treatment systems to mitigate well water contamination.

    PubMed

    Smith, Andrew E; Lincoln, Rebecca A; Paulu, Chris; Simones, Thomas L; Caldwell, Kathleen L; Jones, Robert L; Backer, Lorraine C

    2016-02-15

    There is little published literature on the efficacy of strategies to reduce exposure to residential well water arsenic. The objectives of our study were to: 1) determine if water arsenic remained a significant exposure source in households using bottled water or point-of-use treatment systems; and 2) evaluate the major sources and routes of any remaining arsenic exposure. We conducted a cross-sectional study of 167 households in Maine using one of these two strategies to prevent exposure to arsenic. Most households included one adult and at least one child. Untreated well water arsenic concentrations ranged from <10 μg/L to 640 μg/L. Urine samples, water samples, daily diet and bathing diaries, and household dietary and water use habit surveys were collected. Generalized estimating equations were used to model the relationship between urinary arsenic and untreated well water arsenic concentration, while accounting for documented consumption of untreated water and dietary sources. If mitigation strategies were fully effective, there should be no relationship between urinary arsenic and well water arsenic. To the contrary, we found that untreated arsenic water concentration remained a significant (p ≤ 0.001) predictor of urinary arsenic levels. When untreated water arsenic concentrations were <40 μg/L, untreated water arsenic was no longer a significant predictor of urinary arsenic. Time spent bathing (alone or in combination with water arsenic concentration) was not associated with urinary arsenic. A predictive analysis of the average study participant suggested that when untreated water arsenic ranged from 100 to 500 μg/L, elimination of any untreated water use would result in an 8%-32% reduction in urinary arsenic for young children, and a 14%-59% reduction for adults. These results demonstrate the importance of complying with a point-of-use or bottled water exposure reduction strategy. However, there remained unexplained, water-related routes of exposure.

  9. Evaluation of Exposure to Arsenic in Residential Soil

    SciTech Connect

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

    2005-12-01

    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 ?g/L, respectively) and older participants (3.8, 1.9, 0.91?19.9 ?g/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.

  10. Urinary Incontinence

    MedlinePlus

    ... It may begin around the time of menopause. Urgency urinary incontinence happens when people have a sudden need ... urinary incontinence is a mix of stress and urgency urinary incontinence. You may leak urine with a laugh ...

  11. Differential DNA methylation profile of key genes in malignant prostate epithelial cells transformed by inorganic arsenic or cadmium.

    PubMed

    Pelch, Katherine E; Tokar, Erik J; Merrick, B Alex; Waalkes, Michael P

    2015-08-01

    Previous work shows altered methylation patterns in inorganic arsenic (iAs)- or cadmium (Cd)-transformed epithelial cells. Here, the methylation status near the transcriptional start site was assessed in the normal human prostate epithelial cell line (RWPE-1) that was malignantly transformed by 10μM Cd for 11weeks (CTPE) or 5μM iAs for 29weeks (CAsE-PE), at which time cells showed multiple markers of acquired cancer phenotype. Next generation sequencing of the transcriptome of CAsE-PE cells identified multiple dysregulated genes. Of the most highly dysregulated genes, five genes that can be relevant to the carcinogenic process (S100P, HYAL1, NTM, NES, ALDH1A1) were chosen for an in-depth analysis of the DNA methylation profile. DNA was isolated, bisulfite converted, and combined bisulfite restriction analysis was used to identify differentially methylated CpG sites, which was confirmed with bisulfite sequencing. Four of the five genes showed differential methylation in transformants relative to control cells that was inversely related to altered gene expression. Increased expression of HYAL1 (>25-fold) and S100P (>40-fold) in transformants was correlated with hypomethylation near the transcriptional start site. Decreased expression of NES (>15-fold) and NTM (>1000-fold) in transformants was correlated with hypermethylation near the transcriptional start site. ALDH1A1 expression was differentially expressed in transformed cells but was not differentially methylated relative to control. In conclusion, altered gene expression observed in Cd and iAs transformed cells may result from altered DNA methylation status.

  12. Mild recessive mutations in six Fraser syndrome-related genes cause isolated congenital anomalies of the kidney and urinary tract.

    PubMed

    Kohl, Stefan; Hwang, Daw-Yang; Dworschak, Gabriel C; Hilger, Alina C; Saisawat, Pawaree; Vivante, Asaf; Stajic, Natasa; Bogdanovic, Radovan; Reutter, Heiko M; Kehinde, Elijah O; Tasic, Velibor; Hildebrandt, Friedhelm

    2014-09-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) account for approximately 40% of children with ESRD in the United States. Hitherto, mutations in 23 genes have been described as causing autosomal dominant isolated CAKUT in humans. However, >90% of cases of isolated CAKUT still remain without a molecular diagnosis. Here, we hypothesized that genes mutated in recessive mouse models with the specific CAKUT phenotype of unilateral renal agenesis may also be mutated in humans with isolated CAKUT. We applied next-generation sequencing technology for targeted exon sequencing of 12 recessive murine candidate genes in 574 individuals with isolated CAKUT from 590 families. In 15 of 590 families, we identified recessive mutations in the genes FRAS1, FREM2, GRIP1, FREM1, ITGA8, and GREM1, all of which function in the interaction of the ureteric bud and the metanephric mesenchyme. We show that isolated CAKUT may be caused partially by mutations in recessive genes. Our results also indicate that biallelic missense mutations in the Fraser/MOTA/BNAR spectrum genes cause isolated CAKUT, whereas truncating mutations are found in the multiorgan form of Fraser syndrome. The newly identified recessive biallelic mutations in these six genes represent the molecular cause of isolated CAKUT in 2.5% of the 590 affected families in this study.

  13. 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 ...

  14. From gene discovery to new biological mechanisms: heparanases and congenital urinary bladder disease

    PubMed Central

    Roberts, Neil A.; Hilton, Emma N.; Woolf, Adrian S.

    2016-01-01

    We present a scientific investigation into the pathogenesis of a urinary bladder disease. The disease in question is called urofacial syndrome (UFS), a congenital condition inherited in an autosomal recessive manner. UFS features incomplete urinary bladder emptying and vesicoureteric reflux, with a high risk of recurrent urosepsis and end-stage renal disease. The story starts from a human genomic perspective, then proceeds through experiments that seek to determine the roles of the implicated molecules in embryonic frogs and newborn mice. A future aim would be to use such biological knowledge to intelligently choose novel therapies for UFS. We focus on heparanase proteins and the peripheral nervous system, molecules and tissues that appear to be key players in the pathogenesis of UFS and therefore must also be critical for functional differentiation of healthy bladders. These considerations allow the envisioning of novel biological treatments, although the potential difficulties of targeting the developing bladder in vivo should not be underestimated. PMID:26315301

  15. Arsenic (+ 3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice

    SciTech Connect

    Hughes, Michael F.; Edwards, Brenda C.; Herbin-Davis, Karen M.; Saunders, Jesse; Styblo, Miroslav; Thomas, David J.

    2010-12-15

    Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes formation of mono-, di-, and tri-methylated metabolites of inorganic arsenic. Distribution and retention of arsenic were compared in adult female As3mt knockout mice and wild-type C57BL/6 mice using a regimen in which mice received daily oral doses of 0.5 mg of arsenic as arsenate per kilogram of body weight. Regardless of genotype, arsenic body burdens attained steady state after 10 daily doses. At steady state, arsenic body burdens in As3mt knockout mice were 16 to 20 times greater than in wild-type mice. During the post dosing clearance period, arsenic body burdens declined in As3mt knockout mice to {approx} 35% and in wild-type mice to {approx} 10% of steady-state levels. Urinary concentration of arsenic was significantly lower in As3mt knockout mice than in wild-type mice. At steady state, As3mt knockout mice had significantly higher fractions of the body burden of arsenic in liver, kidney, and urinary bladder than did wild-type mice. These organs and lung had significantly higher arsenic concentrations than did corresponding organs from wild-type mice. Inorganic arsenic was the predominant species in tissues of As3mt knockout mice; tissues from wild-type mice contained mixtures of inorganic arsenic and its methylated metabolites. Diminished capacity for arsenic methylation in As3mt knockout mice prolongs retention of inorganic arsenic in tissues and affects whole body clearance of arsenic. Altered retention and tissue tropism of arsenic in As3mt knockout mice could affect the toxic or carcinogenic effects associated with exposure to this metalloid or its methylated metabolites.

  16. Urinary isothiocyanate excretion, brassica consumption, and gene polymorphisms among women living in Shanghai, China.

    PubMed

    Fowke, Jay H; Shu, Xiao-Ou; Dai, Qi; Shintani, Ayumi; Conaway, C Clifford; Chung, Fung-Lung; Cai, Qiuyin; Gao, Yu-Tang; Zheng, Wei

    2003-12-01

    Alternative measures of Brassica vegetable consumption (e.g., cabbage) may clarify the association between Brassica and cancer risk. Brassica isothiocyanates (ITCs) are excreted in urine and may provide a sensitive and food-specific dietary biomarker. However, the persistence of ITCs in the body may be brief and dependent on the activity of several Phase II enzymes, raising questions about the relationship between a single ITC measure and habitual dietary patterns. This study investigates the association between urinary ITC excretion and habitual Brassica consumption, estimated by a food frequency questionnaire, among healthy Chinese women enrolled in the Shanghai Breast Cancer Study. Participants (n = 347) completed a validated food frequency questionnaire querying habitual dietary intake during the prior 5 years and provided a fasting first-morning urine specimen. Genetic deletion of glutathione S-transferases (GSTM1/GSTT1), and single nucleotide substitutions in GSTP1 (A313G) and NAD(P)H:quinone oxidoreductase 1 (NQO1: C609T), were identified from blood DNA. Urinary ITC excretion levels were marginally higher with the GSTT1-null or GSTP1-G/G genotypes (P = 0.07, P = 0.05, respectively). Mean habitual Brassica intake was 98.3 g/day, primarily as bok choy, and Brassica intake significantly increased across quartile categories of ITC levels. The association between habitual Brassica intake and urinary ITC levels was stronger among women with GSTT1-null or GSTP1-A/A genotypes, or NQO1 T-allele, and the interaction was statistically significant across GSTP1 genotype. In conclusion, a single urinary ITC measure, in conjunction with markers of Phase II enzyme activity, provides a complementary measure of habitual Brassica intake among Shanghai women.

  17. 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...

  18. Arsenic trioxide regulates adipogenic and osteogenic differentiation in bone marrow MSCs of aplastic anemia patients through BMP4 gene.

    PubMed

    Cheng, Huan Chen; Liu, Sheng Wei; Li, Wei; Zhao, Xue Fei; Zhao, Xu; Cheng, Mei; Qiu, Lin; Ma, Jun

    2015-09-01

    The typical pathological feature of aplastic anemia (AA) is the rise in the number of fat cells and the reduction of osteoblasts in bone marrow. However, both fat cells and osteobalsts in bone marrow are derived from the mesenchymal stem cells (MSCs). Generally, the adipogenic and osteogenic differentiation is a dynamic and balanceable process. The imbalance of the adipogenic and osteogenic differentiation may participate in the occurrence and progress of many diseases. Arsenic trioxide (ATO) could induce differentiation and apoptosis in tumor cells. In this study, Oil Red-O and Alizarin red were used to detect the adipogenic and osteogenic differentiation. The ability of adipogenic differentiation is much higher, whereas the osteogenic differentiation is much lower in the MSCs of AA patients compared with healthy controls. ATO inhibits adipogenic differentiation and promotes osteogenic differentiation in the MSC of AA patients. The expression of BMP4 is increased with ATO treatment. The ability of adipogenic differentiation is decreased, whereas the osteogenic differentiation is increased after transfection of BMP4 gene into the MSCs of AA patients. This study shows that ATO regulates the adipogenic and osteogenic differentiation balance of MSCs in AA, which provides a theoretical basis for the adjunctive therapy of ATO on AA. The BMP4 gene is involved in the ATO regulation of adipogenic and osteogenic differentiation balance, which provides a new target for the treatment of AA.

  19. GENE EXPRESSION DOSE-RESPONSE IN THE BLADDERS OF MICE EXPOSED TO ARSENIC IN DRINKING WATER FOR 13 WEEKS

    EPA Science Inventory

    The association between drinking water exposures to inorganic arsenic and life-threatening tumors in the human is strongest for bladder cancer. To investigate the mode of action for inorganic arsenic carcinogenicity in the bladder, a study was conducted to characterize the dose-r...

  20. 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....

  1. A Phytoremediation Strategy for Arsenic

    SciTech Connect

    Meagher, Richard B.

    2005-06-01

    A Phytoremediation Strategy for Arsenic Progress Report May, 2005 Richard B. Meagher Principal Investigator Arsenic pollution affects the health of several hundred millions of people world wide, and an estimated 10 million Americans have unsafe levels of arsenic in their drinking water. However, few environmentally sound remedies for cleaning up arsenic contaminated soil and water have been proposed. Phytoremediation, the use of plants to extract and sequester environmental pollutants, is one new technology that offers an ecologically sound solution to a devastating problem. We propose that it is less disruptive to the environment to harvest and dispose of several thousand pounds per acre of contaminated aboveground plant material, than to excavate and dispose of 1 to 5 million pounds of contaminated soil per acre (assumes contamination runs 3 ft deep). Our objective is to develop a genetics-based phytoremediation strategy for arsenic removal that can be used in any plant species. This strategy requires the enhanced expression of several transgenes from diverse sources. Our working hypothesis is that organ-specific expression of several genes controlling the transport, electrochemical state, and binding of arsenic will result in the efficient extraction and hyperaccumulation of arsenic into aboveground plant tissues. This hypothesis is supported by theoretical arguments and strong preliminary data. We proposed six Specific Aims focused on testing and developing this arsenic phytoremediation strategy. During the first 18 months of the grant we made significant progress on five Specific Aims and began work on the sixth as summarized below. Specific Aim 1: Enhance plant arsenic resistance and greatly expand sinks for arsenite by expressing elevated levels of thiol-rich, arsenic-binding peptides. Hyperaccumulation of arsenic depends upon making plants that are both highly tolerant to arsenic and that have the capacity to store large amounts of arsenic aboveground

  2. Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men.

    PubMed

    Nishimura, H; Yerkes, E; Hohenfellner, K; Miyazaki, Y; Ma, J; Hunley, T E; Yoshida, H; Ichiki, T; Threadgill, D; Phillips, J A; Hogan, B M; Fogo, A; Brock, J W; Inagami, T; Ichikawa, I

    1999-01-01

    Angiotensin type 2 receptor gene null mutant mice display congenital anomalies of the kidney and urinary tract (CAKUT). Various features of mouse CAKUT impressively mimic human CAKUT. Studies of the human type 2 receptor (AGTR2) gene in two independent cohorts found that a significant association exists between CAKUT and a nucleotide transition within the lariat branchpoint motif of intron 1, which perturbs AGTR2 mRNA splicing efficiency. AGTR2, therefore, has a significant ontogenic role for the kidney and urinary tract system. Studies revealed that the establishment of CAKUT is preceded by delayed apoptosis of undifferentiated mesenchymal cells surrounding the urinary tract during key ontogenic events, from the ureteral budding to the expansive growth of the kidney and ureter.

  3. Arsenic contamination of Ronphibun residents associated with uses of arsenic-contaminated shallow-well water other than drinking.

    PubMed

    Oshikawa, Shoko; Geater, Alan; Chongsuvivatwong, Virasakdi; Chakraborti, Dipankar

    2007-10-01

    High levels of urinary arsenic have been reported among residents of an area of southern Thailand where many households have shallow wells heavily contaminated with arsenic. However, the finding that very few of the residents in this area have used contaminated shallow-well water for drinking or cooking in the last 10 years prompted this investigation. The aim was to identify the uses of shallow-well water by adult residents that were related to a positive association between shallow-well water and urinary arsenic levels. Information on shallow-well water use for all personal and domestic purposes was obtained and arsenic levels of household shallow-well water and urine (after refraining from seafood for 2 days) were measured. Urinary and shallow-well water arsenic levels were strongly positively associated among residents who regularly used shallow-well water for bathing (including washing face, hair, hands and feet) but not among residents regularly using arsenic-safe water for bathing or regularly using shallow-well water for other purposes, such as brushing teeth, domestic cleaning or washing food and utensils. The findings suggest that appreciable transdermal absorption of arsenic is possible and that successful abatement of human contamination with arsenic may require the provision of arsenic-safe water, not only for consumption but also for personal hygiene purposes.

  4. Linking Microbial Activity with Arsenic Fate during Cow Dung Disposal of Arsenic-Bearing Wastes

    NASA Astrophysics Data System (ADS)

    Clancy, T. M.; Reddy, R.; Tan, J.; Hayes, K. F.; Raskin, L.

    2014-12-01

    To address widespread arsenic contamination of drinking water sources numerous technologies have been developed to remove arsenic. All technologies result in the production of an arsenic-bearing waste that must be evaluated and disposed in a manner to limit the potential for environmental release and human exposure. One disposal option that is commonly recommended for areas without access to landfills is the mixing of arsenic-bearing wastes with cow dung. These recommendations are made based on the ability of microorganisms to create volatile arsenic species (including mono-, di-, and tri-methylarsine gases) to be diluted in the atmosphere. However, most studies of environmental microbial communities have found only a small fraction (<0.1 %) of the total arsenic present in soils or rice paddies is released via volatilization. Additionally, past studies often have not monitored arsenic release in the aqueous phase. Two main pathways for microbial arsenic volatilization are known and include methylation of arsenic during methanogenesis and methylation by arsenite S-adenosylmethionine methyltransferase. In this study, we compare the roles of these two pathways in arsenic volatilization and aqueous mobilization through mesocosm experiments with cow dung and arsenic-bearing wastes produced during drinking water treatment in West Bengal, India. Arsenic in gaseous, aqueous, and solid phases was measured. Consistent with previous reports, less than 0.02% of the total arsenic present was volatilized. A much higher amount (~5%) of the total arsenic was mobilized into the liquid phase. Through the application of molecular tools, including 16S rRNA sequencing and quantification of gene transcripts involved in methanogenesis, this study links microbial community activity with arsenic fate in potential disposal environments. These results illustrate that disposal of arsenic-bearing wastes by mixing with cow dung does not achieve its end goal of promoting arsenic volatilization

  5. Possible Positive Selection for an Arsenic-Protective Haplotype in Humans

    PubMed Central

    Schlebusch, Carina M.; Lewis, Cecil M.; Vahter, Marie; Engström, Karin; Tito, Raúl Y.; Obregón-Tito, Alexandra J.; Huerta, Doris; Polo, Susan I.; Medina, Ángel C.; Brutsaert, Tom D.; Concha, Gabriela; Jakobsson, Mattias

    2012-01-01

    Background: Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplotype associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite. Objectives: We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplotype frequencies among different indigenous groups. Methods: Indigenous groups we evaluated were a) inhabitants of SAC and villages near Salta in northern Argentina (n = 346), b) three Native American populations from the Human Genome Diversity Project (HGDP; n = 25), and c) five Peruvian populations (n = 97). The last two groups have presumably lower historical exposure to arsenic. Results: We found a significantly higher frequency of the protective AS3MT haplotype in the SAC population (68.7%) compared with the HGDP (14.3%, p < 0.001, Fisher exact test) and Peruvian (50.5%, p < 0.001) populations. Genome-wide microsatellite (n = 671) analysis showed no detectable level of population structure between SAC and Peruvian populations (measure of population differentiation FST = 0.006) and low levels of structure between SAC and HGDP populations (FST < 0.055 for all pairs of populations compared). Conclusions: Because population stratification seems unlikely to explain the differences in AS3MT haplotype frequencies, our data raise the possibility that, during a few thousand years, natural selection for tolerance to the environmental stressor arsenic may have increased the frequency of protective variants of AS3MT. Further studies are needed to investigate this hypothesis. PMID:23070617

  6. Methylation of Inorganic Arsenic by Murine Fetal Tissue Explants

    PubMed Central

    Broka, Derrick; Ditzel, Eric; Quach, Stephanie; Camenisch, Todd D.

    2016-01-01

    Although it is generally believed that the developing fetus is principally exposed to inorganic arsenic and the methylated metabolites from the maternal metabolism of arsenic, little is known about whether the developing embryo can autonomously metabolize arsenic. This study investigates inorganic arsenic methylation by murine embryonic organ cultures of the heart, lung, and liver. mRNA for AS3mt, the gene responsible for methylation of arsenic, was detected in all of embryonic tissue types studied. In addition, methylated arsenic metabolites were generated by all three tissue types. The fetal liver explants yielded the most methylated arsenic metabolites (~7% of total arsenic/ 48 hr incubation) while the heart, and lung preparations produced slightly greater than 2% methylated metabolites. With all tissues the methylation proceeded mostly to the dimethylated arsenic species. This has profound implications for understanding arsenic-induced fetal toxicity, particularly if the methylated metabolites are produced autonomously by embryonic tissues. PMID:26446802

  7. Arsenic tolerances in rice (Oryza sativa) have a predominant role in transcriptional regulation of a set of genes including sulphur assimilation pathway and antioxidant system.

    PubMed

    Rai, Arti; Tripathi, Preeti; Dwivedi, Sanjay; Dubey, Sonali; Shri, Manju; Kumar, Smita; Tripathi, Pankaj Kumar; Dave, Richa; Kumar, Amit; Singh, Ragini; Adhikari, Bijan; Bag, Manas; Tripathi, Rudra Deo; Trivedi, Prabodh K; Chakrabarty, Debasis; Tuli, Rakesh

    2011-02-01

    World wide arsenic (As) contamination of rice has raised much concern as it is the staple crop for millions. Four most commonly cultivated rice cultivars, Triguna, IR-36, PNR-519 and IET-4786, of the West Bengal region were taken for a hydroponic study to examine the effect of arsenate (As(V)) and arsenite (As(III)) on growth response, expression of genes and antioxidants vis-à-vis As accumulation. The rice genotypes responded differentially under As(V) and As(III) stress in terms of gene expression and antioxidant defences. Some of the transporters were up-regulated in all rice cultivars at lower doses of As species, except IET-4786. Phytochelatin synthase, GST and γ-ECS showed considerable variation in their expression pattern in all genotypes, however in IET-4786 they were generally down-regulated in higher As(III) stress. Similarly, most of antioxidants such as superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT), monodehydroascorbate reductase (MDHAR) and dehydroascorbate reductase (DHAR) increased significantly in Triguna, IR-36 and PNR-519 and decreased in IET-4786. Our study suggests that Triguna, IR-36 and PNR-519 are tolerant rice cultivars accumulating higher arsenic; however IET-4786 is susceptible to As-stress and accumulates less arsenic than other cultivars.

  8. Arsenic, Anaerobes, and Astrobiology

    NASA Astrophysics Data System (ADS)

    Stolz, J. F.; Oremland, R. S.; Switzer Blum, J.; Hoeft, S. E.; Baesman, S. M.; Bennett, S.; Miller, L. G.; Kulp, T. R.; Saltikov, C.

    2013-12-01

    Arsenic is an element best known for its highly poisonous nature, so it is not something one would associate with being a well-spring for life. Yet discoveries made over the past two decades have delineated that not only are some microbes resistant to arsenic, but that this element's primary redox states can be exploited to conserve energy and support prokaryotic growth ('arsenotrophy') in the absence of oxygen. Hence, arsenite [As(III)] can serve as an electron donor for chemo- or photo-autotrophy while arsenate [As(V)] will serve as an electron acceptor for chemo-heterotrophs and chemo-autotrophs. The phylogenetic diversity of these microbes is broad, encompassing many individual species from diverse taxonomic groups in the Domain Bacteria, with fewer representatives in the Domain Archaea. Speculation with regard to the evolutionary origins of the key functional genes in anaerobic arsenic transformations (arrA and arxA) and aerobic oxidation (aioB) has led to a disputation as to which gene and function is the most ancient and whether arsenic metabolism extended back into the Archaean. Regardless of its origin, robust arsenic metabolism has been documented in extreme environments that are rich in their arsenic content, such as hot springs and especially hypersaline soda lakes associated with volcanic regions. Searles Lake, CA is an extreme, salt-saturated end member where vigorous arsenic metabolism occurs, but there is no detectable sulfate-reduction or methanogenesis. The latter processes are too weak bio-energetically to survive as compared with arsenotrophy, and are also highly sensitive to the abundance of borate ions present in these locales. These observations have implications with respect to the search for microbial life elsewhere in the Solar System where volcanic-like processes have been operative. Hence, because of the likelihood of encountering dense brines in the regolith of Mars (formed by evapo-concentration) or beneath the ice layers of Europa

  9. Subcellular distribution, modulation of antioxidant and stress-related genes response to arsenic in Brassica napus L.

    PubMed

    Farooq, Muhammad A; Gill, Rafaqat A; Ali, Basharat; Wang, Jian; Islam, Faisal; Ali, Shafaqat; Zhou, Weijun

    2016-03-01

    Arsenic (As) is an environmental toxin pollutant that affects the numerous physiological processes of plants. In present study, two Brassica napus L. cultivars were subjected to various concentrations (0, 50, 100, and 200 µM) of As for 14 days, plants were examined for As subcellular distribution, photosynthesis parameters, oxidative stress, and ultrastructural changes under As-stress. Differential fraction analysis showed that significant amount of As was accumulated in the cell wall as compared to other organelles. Decline in photosynthetic efficiency under As stress was observed in term of reduced pigment contents and gas exchange parameters. Differential responses of antioxidants at both enzymatic and gene levels to higher As stress were more pronounced in cultivar ZS 758 as compared to Zheda 622. The qRT-PCR analysis showed that heat shock protein 90 (Hsp90) and metallothionein were over-expressed in As stressed B. napus plants. Disorganization of cell structure and the damages in different organelles were some of the obvious variations in cultivar Zheda 622 as compared to ZS 758.

  10. Low-level arsenic exposure in wood processing plants.

    PubMed

    Rosenberg, M J; Landrigan, P J; Crowley, S

    1980-01-01

    In October 1978, seven construction workers building a pier in Monterey, California, developed symptoms consistent with arsenic intoxication and had elevated urinary levels of arsenic. The wood used for the pier had been pressure-treated with an arsenic preservative. To evaluate the potential acute medical hazards of preserving wood with arsenic, we evaluated employees at three California plants where arsenic preservatives are mixed and applied to wood. Histories, physical examinations, and urine specimens for arsenic analysis were collected from 44 workers exposed to arsenic and from 37 controls in three woodworking plants where arsenic is not used. A comparison of the groups failed to show any significant differences in history or physical examination. Adjustment for age, length of employment, and smoking histories did not alter the pattern. Urinary arsenic concentration was found to increase with increased exposure. These results do not imply absence of chronic or delayed toxicity, nor do they preclude the presence of a more subtle toxicity such as nerve conduction deficits. The data indicate existence of an arsenic exposure hazard in wood processing.U

  11. Accelerated evolution of CES7, a gene encoding a novel major urinary protein in the cat family.

    PubMed

    Li, Gang; Janecka, Jan E; Murphy, William J

    2011-02-01

    Cauxin is a novel urinary protein recently identified in the domestic cat that regulates the excretion of felinine, a pheromone precursor involved in sociochemical communication and territorial marking of domestic and wild felids. Understanding the evolutionary history of cauxin may therefore illuminate molecular adaptations involved in the evolution of pheromone-based communication, recognition, and mate selection in wild animals. We sequenced the gene encoding cauxin, CES7, in 22 species representing all major felid lineages, and multiple outgroups and showed that it has undergone rapid evolutionary change preceding and during the diversification of the cat family. A comparison between feline cauxin and orthologous carboxylesterases from other mammalian lineages revealed evidence of strong positive Darwinian selection within and between several cat lineages, enriched at functionally important sites of the protein. The higher rate of radical amino acid replacements in small felids, coupled with the lack of felinine and extremely low levels of cauxin in the urine of the great cats (Panthera), correlates with functional divergence of this gene in Panthera, and its putative loss in the snow leopard. Expression studies found evidence for several alternatively spliced transcripts in testis and brain, suggesting additional roles in male reproductive fitness and behavior. Our work presents the first report of strong positive natural selection acting on a major urinary protein of nonrodent mammals, providing evidence for parallel selection pressure on the regulation of pheromones in different mammalian lineages, despite the use of different metabolic pathways. Our results imply that natural selection may drive rapid changes in the regulation of pheromones in urine among the different cat species, which in turn may influence social behavior, such as territorial marking and conspecific recognition, therefore serving as an important mechanism for the radiation of this group

  12. GT-repeat polymorphism in the heme oxygenase-1 gene promoter is associated with cardiovascular mortality risk in an arsenic-exposed population in northeastern Taiwan

    SciTech Connect

    Wu, Meei-Maan; Chiou, Hung-Yi; Chen, Chi-Ling; Wang, Yuan-Hung; Hsieh, Yi-Chen; Lien, Li-Ming; Lee, Te-Chang; Chen, Chien-Jen

    2010-11-01

    Inorganic arsenic has been associated with increased risk of atherosclerotic vascular disease and mortality in humans. A functional GT-repeat polymorphism in the heme oxygenase-1 (HO-1) gene promoter is inversely correlated with the development of coronary artery disease and restenosis after clinical angioplasty. The relationship of HO-1 genotype with arsenic-associated cardiovascular disease has not been studied. In this study, we evaluated the relationship between the HO-1 GT-repeat polymorphism and cardiovascular mortality in an arsenic-exposed population. A total of 504 study participants were followed up for a median of 10.7 years for occurrence of cardiovascular deaths (coronary heart disease, cerebrovascular disease, and peripheral arterial disease). Cardiovascular risk factors and DNA samples for determination of HO-1 GT repeats were obtained at recruitment. GT repeats variants were grouped into the S (< 27 repeats) or L allele ({>=} 27 repeats). Relative mortality risk was estimated using Cox regression analysis, adjusted for competing risk of cancer and other causes. For the L/L, L/S, and S/S genotype groups, the crude mortalities for cardiovascular disease were 8.42, 3.10, and 2.85 cases/1000 person-years, respectively. After adjusting for conventional cardiovascular risk factors and competing risk of cancer and other causes, carriers with class S allele (L/S or S/S genotypes) had a significantly reduced risk of cardiovascular mortality compared to non-carriers (L/L genotype) [OR, 0.38; 95% CI, 0.16-0.90]. In contrast, no significant association was observed between HO-1 genotype and cancer mortality or mortality from other causes. Shorter (GT)n repeats in the HO-1 gene promoter may confer protective effects against cardiovascular mortality related to arsenic exposure.

  13. The joint effects of arsenic and risk diplotypes of insulin-like growth factor binding protein-3 in renal cell carcinoma.

    PubMed

    Huang, Chao-Yuan; Huang, Ya-Li; Pu, Yeong-Shiau; Shiue, Horng-Sheng; Chen, Wei-Jen; Chen, Shih-Shan; Lin, Ying-Chin; Su, Chien-Tien; Hsueh, Yu-Mei

    2016-07-01

    The association between renal cell carcinoma (RCC) and diabetes mellitus (DM), alcohol consumption, insulin-like growth factor binding protein-3 (IGFBP-3) gene, and arsenic exposure, has been the subject of independent studies. However, few studies have examined the combined effect of these factors on RCC risk. The aim of this study was to examine the association between these risk factors and the odds ratio (OR) of RCC. A hospital-based case-control study was conducted in 398 RCC patients and 756 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of IRS-1 (Gly972Arg), PI3-K (Met362Ile), IGFBP-3 (A[-202]C), and IGFBP-3 (C[-1590]A) by PCR-RFLP. Profiles of urinary arsenic were measured by high performance liquid chromatography linked with hydride generator and atomic absorption spectrometry. Participants who had never consumed alcohol and who had high total levels of urinary arsenic and DM had a high OR of RCC. IGFBP-3 (A[-202]C) and IGFBP-3 (C[-1590]A) were in linkage disequilibrium. Participants carrying high-risk IGFBP-3 diplotypes A-C/C-C, A-A/A-C, and C-A/C-A had a significantly higher odds ratio (OR) and 95% confidence interval (2.80, 1.91-4.12) of RCC compared to those carrying other IGFBP-3 diplotypes. This is the first study to show that borderline significant interaction of high total levels of urinary arsenic and IGFBP-3 high-risk diplotypes significantly enhanced the OR of RCC. Our data also provide evidence that subjects with more risk factors (e.g., high total levels of urinary arsenic, never consumed alcohol, IGFBP-3 high-risk diplotypes) may experience a higher OR of RCC.

  14. Identification of Virulence Factors Genes in Escherichia coli Isolates from Women with Urinary Tract Infection in Mexico

    PubMed Central

    López-Banda, Daniela A.; Carrillo-Casas, Erika M.; Orozco-Hoyuela, Gabriel; Manjarrez-Hernández, Ángel H.; Arroyo-Escalante, Sara; Moncada-Barrón, David; Villanueva-Recillas, Silvia; Xicohtencatl-Cortes, Juan; Hernández-Castro, Rigoberto

    2014-01-01

    E coli isolates (108) from Mexican women, clinically diagnosed with urinary tract infection, were screened to identify virulence genes, phylogenetic groups, and antibiotic resistance. Isolates were identified by MicroScan4 system; additionally, the minimum inhibitory concentration (MIC) was assessed. The phylogenetic groups and 16 virulence genes encoding adhesins, toxins, siderophores, lipopolysaccharide (LPS), and invasins were identified by PCR. Phylogenetic groups distribution was as follows: B1 9.3%, A 30.6%, B2 55.6%, and D 4.6%. Virulence genes prevalence was ecp 98.1%, fimH 86.1%, traT 77.8%, sfa/focDE 74.1%, papC 62%, iutA 48.1%, fyuA 44.4%, focG 2.8%, sfaS 1.9%, hlyA 7.4%, cnf-1 6.5%, cdt-B 0.9%, cvaC 2.8%, ibeA 2.8%, and rfc 0.9%. Regarding antimicrobial resistance it was above 50% to ampicillin/sulbactam, ampicillin, piperacillin, trimethoprim/sulfamethoxazole, ciprofloxacin, and levofloxacin. Uropathogenic E. coli clustered mainly in the pathogenic phylogenetic group B2. The isolates showed a high presence of siderophores and adhesion genes and a low presence of genes encoding toxins. The high frequency of papC gene suggests that these isolates have the ability to colonize the kidneys. High resistance to drugs considered as first choice treatment such as trimethoprim/sulfamethoxazole and fluoroquinolones was consistently observed. PMID:24895634

  15. DNA fragmentation, caspase 3 and prostate-specific antigen genes expression induced by arsenic, cadmium, and chromium on nontumorigenic human prostate cells.

    PubMed

    El-Atta, Hend M Abo; El-Bakary, Amal A; Attia, Afaf M; Lotfy, Ahmed; Khater, Shery S; Elsamanoudy, Ayman Z; Abdalla, Hussein Abdelaziz

    2014-12-01

    Prostate cancer is one of the most common cancers and the second cause of cancer-related deaths among men. Metals are recognized as chemical carcinogens where chronic exposures to such metals are implicated in the development of cancer, including prostate cancer. This in vitro study demonstrates the relative death sensitivity of prostatic (RWPE-1) cells to arsenic (As), cadmium (Cd), and chromium (Cr) as environmental pollutants through its apoptotic effects and the effect of these chemicals on prostate-specific antigen (PSA) gene expression as a marker for their carcinogecity. RWPE-1 cells were divided into three groups that were treated with As, Cd, and Cr in three replicates, at three different concentrations for each metal for 48 h. A control group consisted of untreated RWPE1 cells was used. Apoptosis was assessed using comet assay and caspase 3 gene expression; meanwhile, PSA gene expression was evaluated by semiqualitative real-time PCR (RT-PCR). One of the novel findings of this study is that arsenic and cadmium at low concentrations decreased apoptosis of RWPE-1 cells in a concentration-dependent manner while chromium induced significant concentration-dependent increase in apoptosis. Yet, at the highest concentrations, apoptosis was relatively more induced by all chemicals. Arsenic was the most chemical inhibiting apoptosis in RWPE-1 cells at low concentration. While at the moderate and highest concentrations, cadmium was the most inhibiting chemical of RWPE-1 cells' apoptosis. No distinct differences between treated and untreated cells for PSA gene expression were observed. It can be concluded that As and Cd, at low concentrations, can reduce apoptosis of prostatic cells in a concentration-dependent manner while chromium induced it; however, all metal salts used in this study did not induce PSA gene expression.

  16. Transplacental arsenic carcinogenesis in mice

    SciTech Connect

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

    2007-08-01

    Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show that 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 days 8 to 18 of gestation, and the offspring were observed for up to 2 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

  17. Elevated Human telomerase reverse transcriptase gene expression in blood cells associated with chronic and arsenic exposure in Inner Mongolia, China

    EPA Science Inventory

    BACKGROUND: Arsenic exposure is associated with human cancer. Telomerase containing the catalytic subunit, human telomerase reverse transcriptase (hTERT), can extend telomeres of chromosomes, delay senescence and promoting cell proliferation leading to tumorigenesis. OBJECTIVE:...

  18. Association of AS3MT polymorphisms and the risk of premalignant arsenic skin lesions

    SciTech Connect

    Valenzuela, Olga L.; Drobna, Zuzana; Hernandez-Castellanos, Erika; Sanchez-Pena, Luz C.; Garcia-Vargas, Gonzalo G.; Borja-Aburto, Victor H.; Styblo, Miroslav; Del Razo, Luz M.

    2009-09-01

    Exposure to naturally occurring inorganic arsenic (iAs), primarily from contaminated drinking water, is considered one of the top environmental health threats worldwide. Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the biotransformation pathway of iAs. AS3MT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to trivalent arsenicals, resulting in the production of methylated (MAs) and dimethylated arsenicals (DMAs). MAs is a susceptibility factor for iAs-induced toxicity. In this study, we evaluated the association of the polymorphism in AS3MT gene with iAs metabolism and with the presence of arsenic (As) premalignant skin lesions. This is a case-control study of 71 cases with skin lesions and 51 controls without skin lesions recruited from a iAs endemic area in Mexico. We measured urinary As metabolites, differentiating the trivalent and pentavalent arsenical species, using the hydride generation atomic absorption spectrometry. In addition, the study subjects were genotyped to analyze three single nucleotide polymorphisms (SNPs), A-477G, T14458C (nonsynonymus SNP; Met287Thr), and T35587C, in the AS3MT gene. We compared the frequencies of the AS3MT alleles, genotypes, and haplotypes in individuals with and without skin lesions. Marginal differences in the frequencies of the Met287Thr genotype were identified between individuals with and without premalignant skin lesions (p = 0.055): individuals carrying the C (TC+CC) allele (Thr) were at risk [odds ratio = 4.28; 95% confidence interval (1.0-18.5)]. Also, individuals with C allele of Met287Thr displayed greater percentage of MAs in urine and decrease in the percentage of DMAs. These findings indicate that Met287Thr influences the susceptibility to premalignant As skin lesions and might be at increased risk for other adverse health effects of iAs exposure.

  19. Systematic Review and Meta-analysis of Candidate Gene Association Studies of Lower Urinary Tract Symptoms in Men☆

    PubMed Central

    Cartwright, Rufus; Mangera, Altaf; Tikkinen, Kari A.O.; Rajan, Prabhakar; Pesonen, Jori; Kirby, Anna C.; Thiagamoorthy, Ganesh; Ambrose, Chris; Gonzalez-Maffe, Juan; Bennett, Phillip R.; Palmer, Tom; Walley, Andrew; Järvelin, Marjo-Riitta; Khullar, Vik; Chapple, Chris

    2014-01-01

    Context Although family studies have shown that male lower urinary tract symptoms (LUTS) are highly heritable, no systematic review exists of genetic polymorphisms tested for association with LUTS. Objective To systematically review and meta-analyze studies assessing candidate polymorphisms/genes tested for an association with LUTS, and to assess the strength, consistency, and potential for bias among pooled associations. Evidence acquisition A systematic search of the PubMed and HuGE databases as well as abstracts of major urologic meetings was performed through to January 2013. Case-control studies reporting genetic associations in men with LUTS were included. Reviewers independently and in duplicate screened titles, abstracts, and full texts to determine eligibility, abstracted data, and assessed the credibility of pooled associations according to the interim Venice criteria. Authors were contacted for clarifications if needed. Meta-analyses were performed for variants assessed in more than two studies. Evidence synthesis We identified 74 eligible studies containing data on 70 different genes. A total of 35 meta-analyses were performed with statistical significance in five (ACE, ELAC2, GSTM1, TERT, and VDR). The heterogeneity was high in three of these meta-analyses. The rs731236 variant of the vitamin D receptor had a protective effect for LUTS (odds ratio: 0.64; 95% confidence interval, 0.49–0.83) with moderate heterogeneity (I2 = 27.2%). No evidence for publication bias was identified. Limitations include wide-ranging phenotype definitions for LUTS and limited power in most meta-analyses to detect smaller effect sizes. Conclusions Few putative genetic risk variants have been reliably replicated across populations. We found consistent evidence of a reduced risk of LUTS associated with the common rs731236 variant of the vitamin D receptor gene in our meta-analyses. Patient summary Combining the results from all previous studies of genetic variants that may

  20. Human Arsenic Poisoning Issues in Central-East Indian Locations: Biomarkers and Biochemical Monitoring

    PubMed Central

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

    2007-01-01

    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. PMID:17431310

  1. Urinary Incontinence

    MedlinePlus

    ... urinary incontinence. Initial pilot studies have shown that acupuncture can provide some short-term benefit, but more ... Urology. 2013;190:113. Wang Y, et al. Acupuncture for stress urinary incontinence in adults. Cochrane Database ...

  2. 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.

  3. Impaired arsenic metabolism in children during weaning

    SciTech Connect

    Faengstroem, Britta; Hamadani, Jena; Nermell, Barbro; Grander, Margaretha; Palm, Brita; Vahter, Marie

    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, a 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.

  4. Whole-Exome Sequencing in the molecular diagnosis of individuals with congenital anomalies of kidney and urinary tract and identification of a new causative gene

    PubMed Central

    Bekheirnia, Mir Reza; Bekheirnia, Nasim; Bainbridge, Matthew N.; Gu, Shen; Akdemir, Zeynep Hande Coban; Gambin, Tomek; Janzen, Nicolette K.; Jhangiani, Shalini N.; Muzny, Donna M.; Michael, Mini; Brewer, Eileen D.; Elenberg, Ewa; Kale, Arundhati S.; Riley, Alyssa A.; Swartz, Sarah J.; Scott, Daryl A.; Yang, Yaping; Srivaths, Poyyapakkam R.; Wenderfer, Scott E.; Bodurtha, Joann; Applegate, Carolyn D.; Velinov, Milen; Myers, Angela; Borovik, Lior; Craigen, William J.; Hanchard, Neil A.; Rosenfeld, Jill A.; Lewis, Richard Alan; Gonzales, Edmond T.; Gibbs, Richard A.; Belmont, John W.; Roth, David R.; Eng, Christine; Braun, Michael C.; Lupski, James R.; Lamb, Dolores J.

    2016-01-01

    Purpose To investigate the utility of whole-exome sequencing (WES) to define a molecular diagnosis in patients clinically diagnosed with congenital anomalies of kidney and urinary tract (CAKUT). Methods WES was performed in 62 families with CAKUT. WES data were analyzed for Single Nucleotide Variants (SNVs) in 35 known CAKUT genes, putatively deleterious sequence changes in new candidate genes, and potentially disease-associated copy-number variants (CNVs). Results In approximately 5% of families, pathogenic SNVs were identified in PAX2, HNF1B, and EYA1. Observed phenotypes in these families expand the current understanding about the role of these genes in CAKUT. Four pathogenic CNVs were also identified using two CNV detection tools. In addition, we found one deleterious de novo SNV in FOXP1 among the 62 families with CAKUT. Database of clinical BMGL laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these 8 individuals with FOXP1 SNVs, have syndromic urinary tract defects, implicating this gene in urinary tract development. Conclusion We conclude that WES can be used to identify the molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes. PMID:27657687

  5. Arsenic resistance strategy in Pantoea sp. IMH: Organization, function and evolution of ars genes

    PubMed Central

    Wang, Liying; Zhuang, Xuliang; Zhuang, Guoqiang; Jing, Chuanyong

    2016-01-01

    Pantoea sp. IMH is the only bacterium found in genus Pantoea with a high As resistance capacity, but its molecular mechanism is unknown. Herein, the organization, function, and evolution of ars genes in IMH are studied starting with analysis of the whole genome. Two ars systems - ars1 (arsR1B1C1H1) and ars2 (arsR2B2C2H2) - with low sequence homology and two arsC-like genes, were found in the IMH genome. Both ars1 and ars2 are involved in the As resistance, where ars1 is the major contributor at 15 °C and ars2 at 30 °C. The difference in the behavior of these two ars systems is attributed to the disparate activities of their arsR promoters at different temperatures. Sequence analysis based on concatenated ArsRBC indicates that ars1 and ars2 clusters may be acquired from Franconibacter helveticus LMG23732 and Serratia marcescens (plasmid R478), respectively, by horizontal gene transfer (HGT). Nevertheless, two arsC-like genes, probably arising from the duplication of arsC, do not contribute to the As resistance. Our results indicate that Pantoea sp. IMH acquired two different As resistance genetic systems by HGT, allowing the colonization of changing ecosystems, and highlighting the flexible adaptation of microorganisms to resist As. PMID:27966630

  6. Rice consumption contributes to arsenic exposure in US women

    PubMed Central

    Gilbert-Diamond, Diane; Cottingham, Kathryn L.; Gruber, Joann F.; Punshon, Tracy; Sayarath, Vicki; Gandolfi, A. Jay; Baker, Emily R.; Jackson, Brian P.; Folt, Carol L.; Karagas, Margaret R.

    2011-01-01

    Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n = 73) consumed a median of 28.3 g/d, which is ∼0.5 cup of cooked rice each day. In general linear models adjusted for age and urinary dilution, both rice consumption (g, dry mass/d) and arsenic exposure through water (μg/d) were significantly associated with natural log-transformed total urinary arsenic (, , both P < 0.0001), as well as inorganic arsenic, monomethylarsonic acid, and dimethylarsinic acid (each P < 0.005). Based on total arsenic, consumption of 0.56 cup/d of cooked rice was comparable to drinking 1 L/d of 10 μg As/L water, the current US maximum contaminant limit. US rice consumption varies, averaging ∼0.5 cup/d, with Asian Americans consuming an average of >2 cups/d. Rice arsenic content and speciation also vary, with some strains predominated by dimethylarsinic acid, particularly those grown in the United States. Our findings along with others indicate that rice consumption should be considered when designing arsenic reduction strategies in the United States. PMID:22143778

  7. Presence of Putative Repeat-in-Toxin Gene tosA in Escherichia coli Predicts Successful Colonization of the Urinary Tract

    PubMed Central

    Vigil, Patrick D.; Stapleton, Ann E.; Johnson, James R.; Hooton, Thomas M.; Hodges, Andrew P.; He, Yongqun; Mobley, Harry L. T.

    2011-01-01

    ABSTRACT Uropathogenic Escherichia coli (UPEC) strains, which cause the majority of uncomplicated urinary tract infections (UTIs), carry a unique assortment of virulence or fitness genes. However, no single defining set of virulence or fitness genes has been found in all strains of UPEC, making the differentiation between UPEC and fecal commensal strains of E. coli difficult without the use of animal models of infection or phylogenetic grouping. In the present study, we consider three broad categories of virulence factors simultaneously to better define a combination of virulence factors that predicts success in the urinary tract. A total of 314 strains of E. coli, representing isolates from fecal samples, asymptomatic bacteriuria, complicated UTIs, and uncomplicated bladder and kidney infections, were assessed by multiplex PCR for the presence of 15 virulence or fitness genes encoding adhesins, toxins, and iron acquisition systems. The results confirm previous reports of gene prevalence among isolates from different clinical settings and identify several new patterns of gene associations. One gene, tosA, a putative repeat-in-toxin (RTX) homolog, is present in 11% of fecal strains but 25% of urinary isolates. Whereas tosA-positive strains carry an unusually high number (11.2) of the 15 virulence or fitness genes, tosA-negative strains have an average of only 5.4 virulence or fitness genes. The presence of tosA was predictive of successful colonization of a murine model of infection, even among fecal isolates, and can be used as a marker of pathogenic strains of UPEC within a distinct subset of the B2 lineage. PMID:21540363

  8. IDENTIFYING CRITICAL CYSTEINE RESIDUES IN ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE

    EPA Science Inventory

    Arsenic (+3 oxidation state) methyltransferase (AS3MT) catalyzes methylation of inorganic arsenic to mono, di, and trimethylated arsenicals. Orthologous AS3MT genes in genomes ranging from simple echinoderm to human predict a protein with five conserved cysteine (C) residues. In ...

  9. Comparative Distribution and Retention of Arsenic in Arsenic (+3 Oxidation State) Methyltransferase Knockout and Wild Type Mice

    EPA Science Inventory

    The mouse arsenic (+3 oxidation state) methyltransferase (As3mt) gene encodes a ~ 43 kDa protein that catalyzes conversion of inorganic arsenic into methylated products. Heterologous expression of AS3MT or its silencing by RNA interference controls arsenic methylation phenotypes...

  10. Association of Toll-Like Receptor 4 Gene Polymorphism and Expression with Urinary Tract Infection Types in Adults

    PubMed Central

    Yin, Xiaolin; Hou, Tianwen; Liu, Ying; Chen, Jing; Yao, Zhiyan; Ma, Cuiqing; Yang, Lijuan; Wei, Lin

    2010-01-01

    Background Innate immunity of which Toll-like receptor (TLR) 4 and CXCR1 are key elements plays a central role in the development of urinary tract infection (UTI). Although the relation between the genetics of TLR4 and CXCR1 and UTI is investigated partly, the polymorphisms and expression of TLR4 and CXCR1 in different types of UTI in adults are not extremely clear. Methodology/Principal Findings This study investigates the presence of TLR4 A (896) G and CXCR1 G (2608) C polymorphisms in 129 UTI patients using RFLP-PCR. Gene and allelic prevalence were compared with 248 healthy controls. Flow cytometry was used to detect TLR4 and CXCR1 expression in the monocytes of UTI patients and healthy controls. TLR4 (896) AG genotype and TLR4 (896) G allele had higher prevalence in UTI (especially in acute cystitis and urethritis) patients, whereas CXCR1 (2608) GC genotype and CXCR1 (2608) C allele had lower prevalence in UTI patients than controls. TLR4 expression was significantly lower in chronic UTI patients than in acute pyelonephritis or healthy controls. CXCR1 expression was similar in both controls and patients. TLR4 expression in chronic UTI patients after astragalus treatment was higher than pre-treatment. Conclusions The results indicate the relationship between the carrier status of TLR4 (896) G alleles and the development of UTI, especially acute cystitis and urethritis, in adults. TLR4 expression levels are correlated with chronic UTI. PMID:21151974

  11. European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene

    PubMed Central

    Rafnar, Thorunn; Vermeulen, Sita H.; Sulem, Patrick; Thorleifsson, Gudmar; Aben, Katja K.; Witjes, J. Alfred; Grotenhuis, Anne J.; Verhaegh, Gerald W.; Hulsbergen-van de Kaa, Christina A.; Besenbacher, Soren; Gudbjartsson, Daniel; Stacey, Simon N.; Gudmundsson, Julius; Johannsdottir, Hrefna; Bjarnason, Hjordis; Zanon, Carlo; Helgadottir, Hafdis; Jonasson, Jon Gunnlaugur; Tryggvadottir, Laufey; Jonsson, Eirikur; Geirsson, Gudmundur; Nikulasson, Sigfus; Petursdottir, Vigdis; Bishop, D. Timothy; Chung-Sak, Sei; Choudhury, Ananya; Elliott, Faye; Barrett, Jennifer H.; Knowles, Margaret A.; de Verdier, Petra J.; Ryk, Charlotta; Lindblom, Annika; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Vineis, Paolo; Polidoro, Silvia; Guarrera, Simonetta; Sacerdote, Carlotta; Panadero, Angeles; Sanz-Velez, José I.; Sanchez, Manuel; Valdivia, Gabriel; Garcia-Prats, Maria D.; Hengstler, Jan G.; Selinski, Silvia; Gerullis, Holger; Ovsiannikov, Daniel; Khezri, Abdolaziz; Aminsharifi, Alireza; Malekzadeh, Mahyar; van den Berg, Leonard H.; Ophoff, Roel A.; Veldink, Jan H.; Zeegers, Maurice P.; Kellen, Eliane; Fostinelli, Jacopo; Andreoli, Daniele; Arici, Cecilia; Porru, Stefano; Buntinx, Frank; Ghaderi, Abbas; Golka, Klaus; Mayordomo, José I.; Matullo, Giuseppe; Kumar, Rajiv; Steineck, Gunnar; Kiltie, Anne E.; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari; Kiemeney, Lambertus A.

    2011-01-01

    Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10−11. SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the ‘urogenous contact hypothesis’ that urine production and voiding frequency modify the risk of UBC. PMID:21750109

  12. Draft Genome Sequence of Brevibacterium linens AE038-8, an Extremely Arsenic-Resistant Bacterium

    DOE PAGES

    Maizel, Daniela; Utturkar, Sagar M.; Brown, Steven D.; ...

    2015-04-16

    To understand the arsenic biogeocycles in the groundwaters at Tucumán, Argentina, we isolated Brevibacterium linens sp. strain AE38-8, obtained from arsenic-contaminated well water. This strain is extremely resistant to arsenicals and has arsenic resistance (ars) genes in its genome. Here, we report the draft genome sequence of B. linens AE38-8.

  13. Draft Genome Sequence of Brevibacterium linens AE038-8, an Extremely Arsenic-Resistant Bacterium.

    PubMed

    Maizel, Daniela; Utturkar, Sagar M; Brown, Steven D; Ferrero, Marcela A; Rosen, Barry P

    2015-04-16

    To understand the arsenic biogeocycles in the groundwaters at Tucumán, Argentina, we isolated Brevibacterium linens sp. strain AE38-8, obtained from arsenic-contaminated well water. This strain is extremely resistant to arsenicals and has arsenic resistance (ars) genes in its genome. Here, we report the draft genome sequence of B. linens AE38-8.

  14. Draft Genome Sequence of Brevibacterium linens AE038-8, an Extremely Arsenic-Resistant Bacterium

    PubMed Central

    Maizel, Daniela; Utturkar, Sagar M.; Brown, Steven D.; Ferrero, Marcela A.

    2015-01-01

    To understand the arsenic biogeocycles in the groundwaters at Tucumán, Argentina, we isolated Brevibacterium linens sp. strain AE38-8, obtained from arsenic-contaminated well water. This strain is extremely resistant to arsenicals and has arsenic resistance (ars) genes in its genome. Here, we report the draft genome sequence of B. linens AE38-8. PMID:25883298

  15. Polymorphic trial in oxidative damage of arsenic exposed Vietnamese

    SciTech Connect

    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. - Highlights: > We showed that hOGG1 and APE1 are associated with urinary 8-OHdG concentrations. > We showed the existence of inter-ethnic differences in hOGG1 and APE1 polymorphism. > These polymorphisms is a genetic marker of susceptibility to oxidative stress.

  16. Enhanced Detoxification of Arsenic Under Carbon Starvation: A New Insight into Microbial Arsenic Physiology.

    PubMed

    Nandre, Vinod S; Bachate, Sachin P; Salunkhe, Rahul C; Bagade, Aditi V; Shouche, Yogesh S; Kodam, Kisan M

    2017-05-01

    Nutrient availability in nature influenced the microbial ecology and behavior present in existing environment. In this study, we have focused on isolation of arsenic-oxidizing cultures from arsenic devoid environment and studied effect of carbon starvation on rate of arsenite oxidation. In spite of the absence of arsenic, a total of 40 heterotrophic, aerobic, arsenic-transforming bacterial strains representing 18 different genera were identified. Nineteen bacterial species were isolated from tannery effluent and twenty-one from tannery soil. A strong co-relation between the carbon starvation and arsenic oxidation potential of the isolates obtained from the said niche was observed. Interestingly, low carbon content enhanced the arsenic oxidation ability of the strains across different genera in Proteobacteria obtained. This represents the impact of physiological response of carbon metabolism under metal stress conditions. Enhanced arsenic-oxidizing ability of the strains was validated by the presence of aio gene and RT-PCR, where 0.5- to 26-fold up-regulation of arsenite oxidase gene in different genera was observed. The cultures isolated from tannery environment in this study show predominantly arsenic oxidation ability. This detoxification of arsenic in lack of carbon content can aid in effective in situ arsenic bioremediation.

  17. Impact of life stage and duration of exposure on arsenic-induced proliferative lesions, neoplasia, and gene expression in male C3H mice.

    EPA Science Inventory

    Previous studies have demonstrated increased liver and adrenal tumor incidence in male mice exposed gestationally to 85 ppm inorganic arsenic via the dams’ drinking water. To further characterize age susceptibility to arsenic carcinogenesis we have administered 85 ppm sodium ars...

  18. Arsenic, inorganic

    Integrated Risk Information System (IRIS)

    Arsenic , inorganic ; CASRN 7440 - 38 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinoge

  19. 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 ...

  20. Arsenic Metabolites and Methylation Capacity Among Individuals Living in a Rural Area with Endemic Arseniasis in Inner Mongolia, China.

    PubMed

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

    2016-04-01

    More than 0.3 million individuals are subject to chronic exposure to arsenic via their drinking water in Inner Mongolia, China. To determine arsenic methylation capacity profiles for such individuals, concentrations of urinary arsenic metabolites were measured for 548 subjects using high-performance liquid chromatography and a hydride generator combined with inductively coupled plasma-mass spectrometry. Mean urinary concentrations of dimethylarsonic acid (DMA), monomethylarsonic acid (MMA), inorganic arsenic (iAs), and total arsenic (TAs) were 200.50, 46.71, 52.96, and 300.17 μg/L, respectively. The %iAs, %DMA, and %MMA were 15.98, 69.72, and 14.29%. Mean urinary %iAs and %MMA were higher in males, while urinary %DMA was higher in females. There was a strong positive correlation between %iAs and %MMA, with negative correlations between %iAs and %DMA, and %iAs and %MMA. In addition, %iAs and %MMA were positively associated with total arsenic in drinking water (WAs), while %DMA was negatively related with WAs. Regression analysis indicated that the primary methylation index (PMI) and secondary methylation index (SMI) generally decreased with increasing WAs. Females had a higher arsenic methylation capacity compared to males. Younger subjects had lower primary arsenic methylation capacity. However, the secondary arsenic methylation capacity was hardly affected by age. Moreover, both primary and secondary arsenic methylation capacities were negatively related to WAs.

  1. Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

    PubMed Central

    Ben Zakour, Nouri L.; Totsika, Makrina; Forde, Brian M.; Watts, Rebecca E.; Mabbett, Amanda N.; Szubert, Jan M.; Sarkar, Sohinee; Phan, Minh-Duy; Peters, Kate M.; Petty, Nicola K.; Alikhan, Nabil-Fareed; Sullivan, Mitchell J.; Gawthorne, Jayde A.; Stanton-Cook, Mitchell; Nhu, Nguyen Thi Khanh; Chong, Teik Min; Yin, Wai-Fong; Chan, Kok-Gan; Hancock, Viktoria; Ussery, David W.; Ulett, Glen C.

    2015-01-01

    Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. Our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder. PMID:25667270

  2. [The diagnostic value of microsatellite LOH analysis and the prognostic relevance of angiogenic gene expression in urinary bladder cancer].

    PubMed

    Szarvas, Tibor

    2009-12-01

    Bladder cancer is the second most common malignancy affecting the urinary system. Currently, histology is the only tool that determines therapy and patients' prognosis. As the treatment of non-invasive (Ta/T1) and muscle invasive (T2-T4) bladder tumors are completely different, correct staging is important, although it is often hampered by disturbing factors. Molecular methods offer new prospects for early disease detection, confirmation of unclear histological findings and prognostication. Applying molecular biological methods, the present study is searching for answers to current diagnostic and prognostic problems in bladder carcinoma. We analyzed tumor, blood and/or urine samples of 334 bladder cancer patients and 117 control individuals. Genetic alterations were analyzed in urine samples of patients and controls, both by PCR-based microsatellite loss of heterozigosity (LOH) analysis using 12 fluorescently labeled primers and by DNA hybridization based UroVysion FISH technique using 4 probes, to assess the diagnostic values of these methods. Whole genome microsatellite analysis (with 400 markers) was performed in tumor and blood specimens of bladder cancer patients to find chromosomal regions, the loss of which may be associated with tumor stage. Furthermore, we assessed the prognostic value of Tie2, VEGF, Angiopoietin-1 and -2. We concluded that DNA analysis of voided urine samples by microsatellite analysis and FISH are sensitive and non-invasive methods to detect bladder cancer. Furthermore, we established a panel of microsatellite markers that could differentiate between non-invasive and invasive bladder cancer. However, further analyses in a larger cohort of patients are needed to assess their specificity and sensitivity. Finally, we identified high Ang-2 and low Tie2 gene expression as significant and independent risk factors of tumor recurrence and cancer related survival.

  3. Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

    DOE PAGES

    Beatson, Scott A.; Ben Zakour, Nouri L.; Totsika, Makrina; ...

    2015-05-01

    Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. Here, to understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number ofmore » UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. In conlusion, our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder.« less

  4. The Genetic Architecture of Arsenic Metabolism Efficiency:A SNP-Based Heritability Study of Bangladeshi Adults

    PubMed Central

    Gao, Jianjun; Tong, Lin; Argos, Maria; Bryan, Molly Scannell; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Kibriya, Muhammad G.; Jasmine, Farzana; Slavkovich, Vesna; Graziano, Joseph H.

    2015-01-01

    Background Consumption of arsenic-contaminated drinking water adversely affects health. There is interindividual variation in arsenic metabolism efficiency, partially due to genetic variation in the arsenic methyltransferase (AS3MT) gene region. Objectives The goal of this study was to assess the overall contribution of genetic factors to variation in arsenic metabolism efficiency, as measured by the relative concentration of dimethylarsinic acid (DMA%) in urine. Methods Using data on genome-wide single nucleotide polymorphisms (SNPs) and urinary DMA% for 2,053 arsenic-exposed Bangladeshi individuals, we employed various SNP-based approaches for heritability estimation and polygenic modeling. Results Using data on all participants, the percent variance explained (PVE) for DMA% by all measured and imputed SNPs was 16% (p = 0.08), which was reduced to 5% (p = 0.34) after adjusting for AS3MT SNPs. Using information on close relatives only, the PVE was 63% (p = 0.0002), but decreased to 41% (p = 0.01) after adjusting for AS3MT SNPs. Regional heritability analysis confirmed 10q24.32 (AS3MT) as a major arsenic metabolism locus (PVE = 7%, p = 4.4 × 10–10), but revealed no additional regions. We observed a moderate association between a polygenic score reflecting elevated DMA% (composed of thousands of non-AS3MT SNPs) and reduced skin lesion risk in an independent sample (p < 0.05). We observed no associations for SNPs reported in prior candidate gene studies of arsenic metabolism. Conclusions Our results suggest that there are common variants outside of the AS3MT region that influence arsenic metabolism in Bangladeshi individuals, but the effects of these variants are very weak compared with variants near AS3MT. The high heritability estimates observed using family-based heritability approaches suggest substantial effects for rare variants and/or unmeasured environmental factors. Citation Gao J, Tong L, Argos M, Scannell Bryan M, Ahmed A, Rakibuz-Zaman M, Kibriya MG

  5. 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...

  6. 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...

  7. 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

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

    2015-02-01

    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 was 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 was 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.

  8. 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

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

    SciTech Connect

    Koch, Iris; Sylvester, Steven; Lai, Vivian W.-M.; Owen, Andrew; Reimer, Kenneth J. Cullen, William R.

    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 into 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.

  10. 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.

  11. Polymorphisms in the XPC gene affect urinary bladder cancer risk: a case-control study, meta-analyses and trial sequential analyses

    PubMed Central

    Sankhwar, Monica; Sankhwar, Satya Narayan; Bansal, Sandeep Kumar; Gupta, Gopal; Rajender, Singh

    2016-01-01

    Compromised activity of the DNA repair enzymes may raise the risk of a number of cancers. We analyzed polymorphisms in the Xeroderma Pigmentosum, Complementation Group C (XPC) gene for their correlation with urinary bladder cancer. Ala499Val and Lys939Gln polymorphisms were genotyped in 234 urinary bladder cancer cases and 258 control samples. A significant association between Ala499Val polymorphism and bladder cancer was observed (OR = 1.78, CI = 1.19–2.66, p = 0.005); however, Lys939Gln was unrelated (OR = 0.97, CI = 0.65–1.45, P = 0.89). Further analysis revealed that Ala499Val was a significant risk factor only in the presence of smoking (OR = 2.23, CI = 1.28–3.87, p < 0.004) or tobacco chewing (OR = 2.40, CI = 1.43–4.04, p = 0.0008). To further appraise the association, we undertook meta-analyses on seven studies (2893 cases and 3056 controls) on Ala499Val polymorphism and eleven studies (5064 cases and 5208 controls) on Lys939Gln polymorphism. Meta-analyses corroborated the above results, showing strong association of Ala499Val (OR = 1.54, CI = 1.21–1.97, p = 0.001) but not that of Lys939Gln (OR = 1.13, CI = 0.95–1.34, p = 0.171) with urinary bladder cancer risk. In conclusion, XPC Ala499Val substitution increases urinary bladder cancer risk, but Lys939Gln appears to be neutral. PMID:27246180

  12. Association of some virulence genes with antibiotic resistance among uropathogenic Escherichia coli isolated from urinary tract infection patients in Alexandria, Egypt: A hospital-based study.

    PubMed

    Alabsi, Mogeeb S; Ghazal, Abeer; Sabry, Soraya A; Alasaly, Monasr M

    2014-06-01

    Uropathogenic Escherichia coli (UPEC) is the infecting agent most frequently involved in urinary tract infections (UTIs) worldwide. UPEC resistance to commonly used antibiotics represents a major health problem all over the world. Several factors have been associated with UPEC resistance to antibiotics. The present study deployed a molecular approach to explore the association between some UPEC virulence genes and antibiotic resistance among patients with UTI in Alexandria, Egypt. The study revealed a significant association between presence of the pap gene and resistance to gentamicin; however, it was not significantly associated with resistance to β-lactam antibiotics, quinolones, aminoglycosides, nitrofurantoin and trimethoprim/sulfamethoxazole. The genes sfa, aer and cnf1 were not significantly associated with UPEC resistance to any of the tested antibiotics. In conclusion, resistance of UPEC isolates in the present study could be attributed to other virulence factors.

  13. Arsenic surveillance program

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Background information about arsenic is presented including forms, common sources, and clinical symptoms of arsenic exposure. The purpose of the Arsenic Surveillance Program and LeRC is outlined, and the specifics of the Medical Surveillance Program for Arsenic Exposure at LeRC are discussed.

  14. Earth Abides Arsenic Biotransformations

    PubMed Central

    Zhu, Yong-Guan; Yoshinaga, Masafumi; Zhao, Fang-Jie; Rosen, Barry P.

    2015-01-01

    Arsenic is the most prevalent environmental toxic element and causes health problems throughout the world. The toxicity, mobility, and fate of arsenic in the environment are largely determined by its speciation, and arsenic speciation changes are driven, at least to some extent, by biological processes. In this article, biotransformation of arsenic is reviewed from the perspective of the formation of Earth and the evolution of life, and the connection between arsenic geochemistry and biology is described. The article provides a comprehensive overview of molecular mechanisms of arsenic redox and methylation cycles as well as other arsenic biotransformations. It also discusses the implications of arsenic biotransformation in environmental remediation and food safety, with particular emphasis on groundwater arsenic contamination and arsenic accumulation in rice. PMID:26778863

  15. Earth Abides Arsenic Biotransformations.

    PubMed

    Zhu, Yong-Guan; Yoshinaga, Masafumi; Zhao, Fang-Jie; Rosen, Barry P

    2014-05-01

    Arsenic is the most prevalent environmental toxic element and causes health problems throughout the world. The toxicity, mobility, and fate of arsenic in the environment are largely determined by its speciation, and arsenic speciation changes are driven, at least to some extent, by biological processes. In this article, biotransformation of arsenic is reviewed from the perspective of the formation of Earth and the evolution of life, and the connection between arsenic geochemistry and biology is described. The article provides a comprehensive overview of molecular mechanisms of arsenic redox and methylation cycles as well as other arsenic biotransformations. It also discusses the implications of arsenic biotransformation in environmental remediation and food safety, with particular emphasis on groundwater arsenic contamination and arsenic accumulation in rice.

  16. Earth Abides Arsenic Biotransformations

    NASA Astrophysics Data System (ADS)

    Zhu, Yong-Guan; Yoshinaga, Masafumi; Zhao, Fang-Jie; Rosen, Barry P.

    2014-05-01

    Arsenic is the most prevalent environmental toxic element and causes health problems throughout the world. The toxicity, mobility, and fate of arsenic in the environment are largely determined by its speciation, and arsenic speciation changes are driven, at least to some extent, by biological processes. In this article, biotransformation of arsenic is reviewed from the perspective of the formation of Earth and the evolution of life, and the connection between arsenic geochemistry and biology is described. The article provides a comprehensive overview of molecular mechanisms of arsenic redox and methylation cycles as well as other arsenic biotransformations. It also discusses the implications of arsenic biotransformation in environmental remediation and food safety, with particular emphasis on groundwater arsenic contamination and arsenic accumulation in rice.

  17. 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.

  18. 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

  19. Polymorphisms of human 8-oxoguanine DNA glycosylase 1 and 8-hydroxydeoxyguanosine increase susceptibility to arsenic methylation capacity-related urothelial carcinoma.

    PubMed

    Huang, Chao-Yuan; Pu, Yeong-Shiau; Shiue, Horng-Sheng; Chen, Wei-Jen; Lin, Ying-Chin; Hsueh, Yu-Mei

    2016-08-01

    Arsenic causes oxidative stress in cultured animal and human cells, and it is a well-documented human carcinogen. We conducted a hospital-based case-control study including 167 cases of urothelial carcinoma (UC) and 334 age- and gender-matched healthy controls to evaluate the relationships between urinary arsenic profiles, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels, and human 8-oxoguanine DNA glycosylase (hOGG1) genotypes and UC. The urinary arsenic species were analyzed by high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Genotyping for hOGG1 (Ser326Cys) and hOGG1 (-15C>G) was performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Urinary 8-OHdG was measured with high-sensitivity enzyme-linked immunosorbent assay kits. The results indicated that the hOGG1 326 Cys/Cys genotype and the hOGG1 -15C>G G/G genotype were associated with an increased risk of UC (OR [95 % CI] 1.57 [1.04-2.35] and 1.57 [1.04-2.35], respectively). Participants with high urinary total arsenic, regardless of the haplotype of hOGG1 Ser326Cys and the -15C>G polymorphism, had significantly higher urinary 8-OHdG compared to participants with low urinary total arsenic. This is the first study to investigate the joint effects of high urinary total arsenic or inefficient arsenic methylation capacity indices, and the high-risk G-G haplotype of hOGG1 on the risk of UC. The findings are especially meaningful for participants with risk factors such as high urinary total arsenic, inefficient arsenic methylation indices, high urinary 8-OHdG, and the high-risk G-G haplotype of hOGG1 which are all associated with an increased UC risk.

  20. Arsenic exposure and hepatitis E virus infection during pregnancy

    PubMed Central

    Heaney, Christopher D.; Kmush, Brittany; Navas-Acien, Ana; Francesconi, Kevin; Gössler, Walter; Schulze, Kerry; Fairweather, DeLisa; Mehra, Sucheta; Nelson, Kenrad E.; Klein, Sabra L.; Li, Wei; Ali, Hasmot; Shaikh, Saijuddin; Merrill, Rebecca D.; Wu, Lee; West, Keith P.; Christian, Parul; Labrique, Alain B.

    2015-01-01

    Background Arsenic has immunomodulatory properties and may have the potential to alter susceptibility to infection in humans. Objectives We aimed to assess the relation of arsenic exposure during pregnancy with immune function and hepatitis E virus (HEV) infection, defined as seroconversion during pregnancy and postpartum. Methods We assessed IgG seroconversion to HEV between 1st and 3rd trimester (TM) and 3 months postpartum (PP) among 1100 pregnancies in a multiple micronutrient supplementation trial in rural Bangladesh. Forty women seroconverted to HEV and were matched with 40 non-seroconverting women (controls) by age, parity and intervention. We assessed urinary inorganic arsenic plus methylated species (∑As) (µg/L) at 1st and 3rd TM and plasma cytokines (pg/mL) at 1st and 3rd TM and 3 months PP. Results HEV seroconverters’ urinary ∑As was elevated throughout pregnancy. Non-seroconverters’ urinary ∑As was similar to HEV seroconverters at 1st TM but declined at 3rd TM. The adjusted odds ratio (95% confidence interval) of HEV seroconversion was 2.17 (1.07, 4.39) per interquartile range (IQR) increase in average-pregnancy urinary ∑As. Increased urinary ∑As was associated with increased concentrations of IL-2 during the 1st and 3rd TM and 3 months PP among HEV seroconverters but not non-seroconverters. Conclusions The relation of urinary arsenic during pregnancy with incident HEV seroconversion and with IL-2 levels among HEV-seroconverting pregnant women suggests arsenic exposure during pregnancy may enhance susceptibility to HEV infection. PMID:26186135

  1. 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

    SciTech Connect

    Suzuki, Shugo; Arnold, Lora L.; Pennington, Karen L.; Chen, Baowei; Naranmandura, Hua; Le, X. Chris; Cohen, Samuel M.

    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 dose 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.

  2. 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.

  3. THE CELLUAR METABOLISM OF ARSENIC

    EPA Science Inventory

    Because the methylation of arsenic produces intermediates and terminal products that exceed inorganic arsenic in potency as enzyme inhibitors, cytotoxins, and genotoxins, the methylation of arsenic is properly regarded as an activation process. The methylation of arsenic is an e...

  4. Mathematical model insights into arsenic detoxification

    PubMed Central

    2011-01-01

    Background Arsenic in drinking water, a major health hazard to millions of people in South and East Asia and in other parts of the world, is ingested primarily as trivalent inorganic arsenic (iAs), which then undergoes hepatic methylation to methylarsonic acid (MMAs) and a second methylation to dimethylarsinic acid (DMAs). Although MMAs and DMAs are also known to be toxic, DMAs is more easily excreted in the urine and therefore methylation has generally been considered a detoxification pathway. A collaborative modeling project between epidemiologists, biologists, and mathematicians has the purpose of explaining existing data on methylation in human studies in Bangladesh and also testing, by mathematical modeling, effects of nutritional supplements that could increase As methylation. Methods We develop a whole body mathematical model of arsenic metabolism including arsenic absorption, storage, methylation, and excretion. The parameters for arsenic methylation in the liver were taken from the biochemical literature. The transport parameters between compartments are largely unknown, so we adjust them so that the model accurately predicts the urine excretion rates of time for the iAs, MMAs, and DMAs in single dose experiments on human subjects. Results We test the model by showing that, with no changes in parameters, it predicts accurately the time courses of urinary excretion in mutiple dose experiments conducted on human subjects. Our main purpose is to use the model to study and interpret the data on the effects of folate supplementation on arsenic methylation and excretion in clinical trials in Bangladesh. Folate supplementation of folate-deficient individuals resulted in a 14% decrease in arsenicals in the blood. This is confirmed by the model and the model predicts that arsenicals in the liver will decrease by 19% and arsenicals in other body stores by 26% in these same individuals. In addition, the model predicts that arsenic methyltransferase has been

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

    SciTech Connect

    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: 8.68–45.71 mg-year) and 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

  6. Chem I Supplement: Arsenic and Old Myths.

    ERIC Educational Resources Information Center

    Sarquis, Mickey

    1979-01-01

    Describes the history of arsenic, the properties of arsenic, production and uses of arsenicals, arsenic in the environment; toxic levels of arsenic, arsenic in the human body, and the Marsh Test. (BT)

  7. 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...

  8. Urinary Retention

    MedlinePlus

    ... indicates the bladder does not empty completely. A health care provider performs this test during an office visit. The patient often receives ... more urodynamic tests to diagnose urinary retention. The health care provider will perform these tests during an office visit. For tests that use ...

  9. Glutathione-S-transferase-omega [MMA(V) reductase] knockout mice: Enzyme and arsenic species concentrations in tissues after arsenate administration

    SciTech Connect

    Chowdhury, Uttam K.; Zakharyan, Robert A.; Hernandez, Alba; Avram, Mihaela D.; Kopplin, Michael J.; Aposhian, H. Vasken . E-mail: aposhian@u.arizona.edu

    2006-11-01

    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 of 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.

  10. The ecology of arsenic

    USGS Publications Warehouse

    Oremland, Ronald S.; Stolz, John F.

    2003-01-01

    Arsenic is a metalloid whose name conjures up images of murder. Nonetheless, certain prokaryotes use arsenic oxyanions for energy generation, either by oxidizing arsenite or by respiring arsenate. These microbes are phylogenetically diverse and occur in a wide range of habitats. Arsenic cycling may take place in the absence of oxygen and can contribute to organic matter oxidation. In aquifers, these microbial reactions may mobilize arsenic from the solid to the aqueous phase, resulting in contaminated drinking water. Here we review what is known about arsenic-metabolizing bacteria and their potential impact on speciation and mobilization of arsenic in nature.

  11. Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: Assessment by real-time PCR array

    EPA Science Inventory

    Arsenic contamination in drinking water has become a great public health concern worldwide. Chronic arsenic exposure results in higher risk of skin, lung and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects o...

  12. Earthworms Produce phytochelatins in Response to Arsenic

    PubMed Central

    Lawlor, Alan J.; Bennett, Mark H.; Morris, Ceri A.; Kille, Peter; Svendsen, Claus; Spurgeon, David J.; Bundy, Jacob G.

    2013-01-01

    Phytochelatins are small cysteine-rich non-ribosomal peptides that chelate soft metal and metalloid ions, such as cadmium and arsenic. They are widely produced by plants and microbes; phytochelatin synthase genes are also present in animal species from several different phyla, but there is still little known about whether these genes are functional in animals, and if so, whether they are metal-responsive. We analysed phytochelatin production by direct chemical analysis in Lumbricus rubellus earthworms exposed to arsenic for a 28 day period, and found that arsenic clearly induced phytochelatin production in a dose-dependent manner. It was necessary to measure the phytochelatin metabolite concentrations directly, as there was no upregulation of phytochelatin synthase gene expression after 28 days: phytochelatin synthesis appears not to be transcriptionally regulated in animals. A further untargetted metabolomic analysis also found changes in metabolites associated with the transsulfuration pathway, which channels sulfur flux from methionine for phytochelatin synthesis. There was no evidence of biological transformation of arsenic (e.g. into methylated species) as a result of laboratory arsenic exposure. Finally, we compared wild populations of earthworms sampled from the field, and found that both arsenic-contaminated and cadmium-contaminated mine site worms had elevated phytochelatin concentrations. PMID:24278409

  13. Earthworms produce phytochelatins in response to arsenic.

    PubMed

    Liebeke, Manuel; Garcia-Perez, Isabel; Anderson, Craig J; Lawlor, Alan J; Bennett, Mark H; Morris, Ceri A; Kille, Peter; Svendsen, Claus; Spurgeon, David J; Bundy, Jacob G

    2013-01-01

    Phytochelatins are small cysteine-rich non-ribosomal peptides that chelate soft metal and metalloid ions, such as cadmium and arsenic. They are widely produced by plants and microbes; phytochelatin synthase genes are also present in animal species from several different phyla, but there is still little known about whether these genes are functional in animals, and if so, whether they are metal-responsive. We analysed phytochelatin production by direct chemical analysis in Lumbricus rubellus earthworms exposed to arsenic for a 28 day period, and found that arsenic clearly induced phytochelatin production in a dose-dependent manner. It was necessary to measure the phytochelatin metabolite concentrations directly, as there was no upregulation of phytochelatin synthase gene expression after 28 days: phytochelatin synthesis appears not to be transcriptionally regulated in animals. A further untargetted metabolomic analysis also found changes in metabolites associated with the transsulfuration pathway, which channels sulfur flux from methionine for phytochelatin synthesis. There was no evidence of biological transformation of arsenic (e.g. into methylated species) as a result of laboratory arsenic exposure. Finally, we compared wild populations of earthworms sampled from the field, and found that both arsenic-contaminated and cadmium-contaminated mine site worms had elevated phytochelatin concentrations.

  14. Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies

    PubMed Central

    Faita, Francesca; Cori, Liliana; Bianchi, Fabrizio; Andreassi, Maria Grazia

    2013-01-01

    The arsenic (As) exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic- health effects. PMID:23583964

  15. Proteus mirabilis Genes That Contribute to Pathogenesis of Urinary Tract Infection: Identification of 25 Signature-Tagged Mutants Attenuated at Least 100-Fold

    PubMed Central

    Burall, Laurel S.; Harro, Janette M.; Li, Xin; Lockatell, C.Virginia; Himpsl, Stephanie D.; Hebel, J. Richard; Johnson, David E.; Mobley, Harry L. T.

    2004-01-01

    Proteus mirabilis, a common cause of urinary tract infections (UTI) in individuals with functional or structural abnormalities or with long-term catheterization, forms bladder and kidney stones as a consequence of urease-mediated urea hydrolysis. Known virulence factors, besides urease, are hemolysin, fimbriae, metalloproteases, and flagella. In this study we utilized the CBA mouse model of ascending UTI to evaluate the colonization of mutants of P. mirabilis HI4320 that were generated by signature-tagged mutagenesis. By performing primary screening of 2,088 P. mirabilis transposon mutants, we identified 502 mutants that ranged from slightly attenuated to unrecoverable. Secondary screening of these mutants revealed that 114 transposon mutants were reproducibly attenuated. Cochallenge of 84 of these single mutants with the parent strain in the mouse model resulted in identification of 37 consistently out-competed P. mirabilis transposon mutants, 25 of which were out-competed >100-fold for colonization of the bladder and/or kidneys by the parent strain. We determined the sequence flanking the site of transposon insertion in 29 attenuated mutants and identified genes affecting motility, iron acquisition, transcriptional regulation, phosphate transport, urease activity, cell surface structure, and key metabolic pathways as requirements for P. mirabilis infection of the urinary tract. Two mutations localized to a ∼42-kb plasmid present in the parent strain, suggesting that the plasmid is important for colonization. Isolation of disrupted genes encoding proteins with homologies to known bacterial virulence factors, especially the urease accessory protein UreF and the disulfide formation protein DsbA, showed that the CBA mouse model and mutant pools are a reliable source of attenuated mutants with mutations in virulence genes. PMID:15102805

  16. Prosaposin Deficiency and Saposin B Deficiency (Activator-Deficient Metachromatic Leukodystrophy): Report on Two Patients Detected by Analysis of Urinary Sphingolipids and Carrying Novel PSAP Gene Mutations

    PubMed Central

    Kuchař, Ladislav; Ledvinová, Jana; Hřebíček, Martin; Myšková, Helena; Dvořáková, Lenka; Berná, Linda; Chrastina, Petr; Asfaw, Befekadu; Elleder, Milan; Petermöller, Margret; Mayrhofer, Heidi; Staudt, Martin; Krägeloh-Mann, Ingeborg; Paton, Barbara C; Harzer, Klaus

    2009-01-01

    Prosaposin deficiency (pSap-d) and saposin B deficiency (SapB-d) are both lipid storage disorders caused by mutations in the PSAP gene that codes for the 65–70 kDa prosaposin protein, which is the precursor for four sphingolipid activator proteins, saposins A–D. We report on two new patients with PSAP gene defects; one, with pSap-d, who had a severe neurovisceral dystrophy and died as a neonate, and the other with SapB-d, who presented with a metachromatic leukodystrophy-like disorder but had normal arylsulfatase activity. Screening for urinary sphingolipids was crucial to the diagnosis of both patients, with electrospray ionization tandem mass spectrometry also providing quantification. The pSap-d patient is the first case with this condition where urinary sphingolipids have been investigated. Multiple sphingolipids were elevated, with globotriaosylceramide showing the greatest increase. Both patients had novel mutations in the PSAP gene. The pSap-d patient was homozygous for a splice-acceptor site mutation two bases upstream of exon 10. This mutation led to a premature stop codon and yielded low levels of transcript. The SapB-d patient was a compound heterozygote with a splice-acceptor site variant exclusively affecting the SapB domain on one allele, and a 2 bp deletion leading to a null, that is, pSap-d mutation, on the other allele. Phenotypically, pSap-d is a relatively uniform disease of the neonate, whereas SapB-d is heterogeneous with a spectrum similar to that in metachromatic leukodystrophy. The possible existence of genotypes and phenotypes intermediate between those of pSap-d and the single saposin deficiencies is speculated. © 2009 Wiley-Liss, Inc. PMID:19267410

  17. Immobilisation of arsenic by iron(II)-oxidizing bacteria

    NASA Astrophysics Data System (ADS)

    Kappler, A.; Hohmann, C.; Winkler, E.; Muehe, M.; Morin, G.

    2008-12-01

    Arsenic-contaminated groundwater is an environmental problem that affects about 1-2% of the world's population. As arsenic-contaminated water is also used for irrigating rice fields, the uptake of arsenic via rice is in some cases even higher than via drinking water. Arsenic is often of geogenic origin and in many cases bound to iron(III) minerals. Microbial iron(III) reduction leads to dissolution of Fe(III) minerals and thus the arsenic bound to these minerals is released to the environment. In turn, iron(II)-oxidizing bacteria have the potential to co-precipitate or sorb arsenic during iron(II) oxidation followed by iron(III) mineral formation. Here, we present work on arsenic co-precipitation and immobilization by anaerobic and aerobic iron(II)-oxidizing bacteria. Co-precipitation batch experiments with pure cultures of nitrate-dependent, phototrophic, and microaerophilic Fe(II)-oxidizing bacteria are used to quantify the amount of arsenic that can be immobilized during microbial iron mineral precipitation. Iron and arsenic speciation and redox state are determined by X- ray diffraction and synchrotron-based X-ray absorption methods (EXAFS, XANES). Microcosm experiments are set-up either with liquid media or with rice paddy soil amended with arsenic. Rice paddy soil from arsenic contaminated rice fields in China that include a natural population of Fe(II)-oxidizing microorganisms is used as inoculum. Dissolved and solid-phase arsenic and iron are quantified, Arsenic speciation is determined and the iron minerals are identified. Additionally, Arsenic uptake into the rice plant is quantified and a gene expression pattern in rice (Oryza sativa cv Gladia) is determined by microarrays as a response to the presence of Fe(II)-oxidizing bacteria.

  18. Arsenic in Food

    MedlinePlus

    ... been measuring total arsenic concentrations in foods, including rice and juices, through its Total Diet Study program ... found in certain food and beverage products, including rice, fruit juices and juice concentrates. How does arsenic ...

  19. Arsenic Treatment Technology Demonstrations

    EPA Pesticide Factsheets

    EPA’s research for the new Arsenic Rule focused on the development and evaluation of innovative methods and cost-effective technologies for improving the assessment and control of arsenic contamination.

  20. Arsenic Trioxide Injection

    MedlinePlus

    Arsenic trioxide is used to treat acute promyelocytic leukemia (APL; a type of cancer in which there ... worsened following treatment with other types of chemotherapy. Arsenic trioxide is in a class of medications called ...

  1. Fact Sheet on Arsenic

    EPA Pesticide Factsheets

    Arsenic is a naturally occurring element that is found in combination with either inorganic or organic substances to form many different compounds. Inorganic arsenic compounds are found in soils, sediments, and groundwater.

  2. Arsenic impacted the development, thyroid hormone and gene transcription of thyroid hormone receptors in bighead carp larvae (Hypophthalmichthys nobilis).

    PubMed

    Sun, Hong-Jie; Xiang, Ping; Tang, Ming-Hu; Sun, Li; Ma, Lena Q

    2016-02-13

    Arsenic (As) contamination in aquatic environment adversely impacts aquatic organisms. The present study assessed the toxicity of different As species and concentrations on bighead carp (Hypophthalmichthys nobilis) at early life stage, a major fish in Yangtze River, China. We measured the changes in embryo and larvae survival rate, larvae aberration, concentrations of thyroid hormone thyroxine, and transcription levels of thyroid hormone receptors (TRs) in fish larvae after exposing to arsenite (AsIII) or arsenate (AsV) at 0, 10, 30, 50, 100, or 150 μg L(-1) for 78 h. As concentrations ≤ 150 μg L(-1) had limited effect on embryo survival rate (6-8% inhibition), but larvae survival rate decreased to 53-57% and larvae aberration rate increased to 20-24% after As exposure. Moreover, thyroxine levels elevated by 23% and 50% at 100 μg L(-1) AsIII and 150 μg L(-1) AsV. Besides, AsIII and AsV decreased the transcriptional levels of TRα by 72 and 53%, and TRβ by 91 and 81% at 150 μg L(-1) As. Our data showed that AsIII and AsV had limited effect on carp embryo survival, but they were both toxic to carp larvae, with AsIII showing more effect than AsV. As concentrations <150μg L(-1) adversely influenced the development of bighead carp larvae and disturbed their thyroid hormone homeostasis.

  3. Elevated lactate dehydrogenase activity and increased cardiovascular mortality in the arsenic-endemic areas of southwestern Taiwan

    SciTech Connect

    Liao, Ya-Tang; Chen, Chien-Jen; Li, Wan-Fen; Hsu, Ling-I; Tsai, Li-Yu; Huang, Yeou-Lih; Sun, Chien-Wen; Chen, Wei J.; Wang, Shu-Li

    2012-08-01

    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 were 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.

  4. [Urinary bilharziasis].

    PubMed

    Gigase, P L

    1992-01-01

    A short account is given of present views on urinary schistosomiasis or bilharziasis. The incidence of infections is increasing in endemic areas of Africa and the near east, as a consequence of irrigation programs and hydroelectric power development. Urinary schistosomiasis is a disease of children and young adults. The serious consequences, obstructive uropathy due to more or less irreversible ureteral lesions, and cancer of the bladder, less directly related to the infection, appear but later in life. Diagnosis is still based on parasitology and serology but ultrasonography has proven to be an important means to evaluate the extent of lesions of the urinary tract, especially in developing countries. Praziquantel was a major development in the medical treatment and cures easily the infection. Some irreversible consequences have however to be treated surgically. Schistosomiasis is still an important cause of morbidity and mortality in medically backward endemic countries. The control of the disease aims at reducing morbidity and mortality, consequences of the infection, rather than to avoid infection itself. It is based on mass treatment of school age children, together with focal molluscacides at places where people have contacts with water. Vaccination will be available in the near future and will be a welcome addition to other control measures, but will not be able to interrupt transmission on its own. Only economic development will solve in the long term this social African problem.

  5. Arsenic inhibits hedgehog signaling during P19 cell differentiation

    SciTech Connect

    Liu, Jui Tung; Bain, Lisa J.

    2014-12-15

    Arsenic is a toxicant found in ground water around the world, and human exposure mainly comes from drinking water or from crops grown in areas containing arsenic in soils or water. Epidemiological studies have shown that arsenic exposure during development decreased intellectual function, reduced birth weight, and altered locomotor activity, while in vitro studies have shown that arsenite decreased muscle and neuronal cell differentiation. The sonic hedgehog (Shh) signaling pathway plays an important role during the differentiation of both neurons and skeletal muscle. The purpose of this study was to investigate whether arsenic can disrupt Shh signaling in P19 mouse embryonic stem cells, leading to changes muscle and neuronal cell differentiation. P19 embryonic stem cells were exposed to 0, 0.25, or 0.5 μM of sodium arsenite for up to 9 days during cell differentiation. We found that arsenite exposure significantly reduced transcript levels of genes in the Shh pathway in both a time and dose-dependent manner. This included the Shh ligand, which was decreased 2- to 3-fold, the Gli2 transcription factor, which was decreased 2- to 3-fold, and its downstream target gene Ascl1, which was decreased 5-fold. GLI2 protein levels and transcriptional activity were also reduced. However, arsenic did not alter GLI2 primary cilium accumulation or nuclear translocation. Moreover, additional extracellular SHH rescued the inhibitory effects of arsenic on cellular differentiation due to an increase in GLI binding activity. Taken together, we conclude that arsenic exposure affected Shh signaling, ultimately decreasing the expression of the Gli2 transcription factor. These results suggest a mechanism by which arsenic disrupts cell differentiation. - Highlights: • Arsenic exposure decreases sonic hedgehog pathway-related gene expression. • Arsenic decreases GLI2 protein levels and transcriptional activity in P19 cells. • Arsenic exposure does not alter the levels of SHH

  6. ARSENIC TREATMENT TECHNOLOGY

    EPA Science Inventory

    Presentation will discuss the state-of-the-art technology for removal of arsenic from drinking water. Presentation also includes results of several EPA field studies on removal of arsenic from existing arsenic removal plants and key results from several EPA sponsored research st...

  7. ARSENIC REMOVAL TECHNOLOGY

    EPA Science Inventory

    Presentation will discuss the state-of-art technology for removal of arsenic from drinking water. Presentation includes results of several EPA field studies on removal of arsenic from existing arsenic removal plants and key results from several EPA sponsored research studies. T...

  8. ARSENIC SOURCES AND ASSESSMENT

    EPA Science Inventory

    Recent research has identified a number of potential and current links between environmental arsenic releases and the management of operational and abandoned landfills. Many landfills will receive an increasing arsenic load due to the disposal of arsenic-bearing solid residuals ...

  9. 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

  10. Case studies--arsenic.

    PubMed

    Chou, C H Selene J; De Rosa, Christopher T

    2003-08-01

    Arsenic is found naturally in the environment. People may be exposed to arsenic by eating food, drinking water, breathing air, or by skin contact with soil or water that contains arsenic. In the U.S., the diet is a predominant source of exposure for the general population with smaller amounts coming from drinking water and air. Children may also be exposed to arsenic because of hand to mouth contact or eating dirt. In addition to the normal levels of arsenic in air, water, soil, and food, people could by exposed to higher levels in several ways such as in areas containing unusually high natural levels of arsenic in rocks which can lead to unusually high levels of arsenic in soil or water. People living in an area like this could take in elevated amounts of arsenic in drinking water. Workers in an occupation that involves arsenic production or use (for example, copper or lead smelting, wood treatment, pesticide application) could be exposed to elevated levels of arsenic at work. People who saw or sand arsenic-treated wood could inhale/ingest some of the sawdust which contains high levels of arsenic. Similarly, when pressure-treated wood is burned, high levels of arsenic could be released in the smoke. In agricultural areas where arsenic pesticides were used on crops the soil could contain high levels of arsenic. Some hazardous waste sites contain large quantities of arsenic. Arsenic ranks #1 on the ATSDR/EPA priority list of hazardous substances. Arsenic has been found in at least 1,014 current or former NPL sites. At the hazardous waster sites evaluated by ATSDR, exposure to arsenic in soil predominated over exposure to water, and no exposure to air had been recorded. However, there is no information on morbidity or mortality from exposure to arsenic in soil at hazardous waste sites. Exposure assessment, community and tribal involvement, and evaluation and surveillance of health effects are among the ATSDR future Superfund research program priority focus areas

  11. Arsenic pollution sources.

    PubMed

    Garelick, Hemda; Jones, Huw; Dybowska, Agnieszka; Valsami-Jones, Eugenia

    2008-01-01

    Arsenic is a widely dispersed element in the Earth's crust and exists at an average concentration of approximately 5 mg/kg. There are many possible routes of human exposure to arsenic from both natural and anthropogenic sources. Arsenic occurs as a constituent in more than 200 minerals, although it primarily exists as arsenopyrite and as a constituent in several other sulfide minerals. The introduction of arsenic into drinking water can occur as a result of its natural geological presence in local bedrock. Arsenic-containing bedrock formations of this sort are known in Bangladesh, West Bengal (India), and regions of China, and many cases of endemic contamination by arsenic with serious consequences to human health are known from these areas. Significant natural contamination of surface waters and soil can arise when arsenic-rich geothermal fluids come into contact with surface waters. When humans are implicated in causing or exacerbating arsenic pollution, the cause can almost always be traced to mining or mining-related activities. Arsenic exists in many oxidation states, with arsenic (III) and (V) being the most common forms. Similar to many metalloids, the prevalence of particular species of arsenic depends greatly on the pH and redox conditions of the matrix in which it exists. Speciation is also important in determining the toxicity of arsenic. Arsenic minerals exist in the environment principally as sulfides, oxides, and phosphates. In igneous rocks, only those of volcanic origin are implicated in high aqueous arsenic concentrations. Sedimentary rocks tend not to bear high arsenic loads, and common matrices such as sands and sandstones contain lower concentrations owing to the dominance of quartz and feldspars. Groundwater contamination by arsenic arises from sources of arsenopyrite, base metal sulfides, realgar and orpiment, arsenic-rich pyrite, and iron oxyhydroxide. Mechanisms by which arsenic is released from minerals are varied and are accounted for by

  12. Arsenic binding to Fucus vesiculosus metallothionein.

    PubMed

    Merrifield, Maureen E; Ngu, Thanh; Stillman, Martin J

    2004-11-05

    The seaweed Fucus vesiculosus is a member of the brown algae family. Kille and co-workers [Biochem. J. 338 (1999) 553] reported that this species contains the gene for metallothionein. Metallothionein is a metalloprotein having low molecular weight, and high cysteine content, which binds a range of metals. F. vesiculosus bioaccumulates arsenic from the aquatic environment [Mar. Chem. 18 (1986) 321]. In this paper we describe arsenic binding to F. vesiculosus metallothionein, characterized by electrospray ionization mass spectrometry. Five arsenic-MT species were detected with increasing As to protein ratios. These results provide important information about the metal-chelation behaviour of this novel algal metallothionein which is a putative model for arsenic binding to F. vesiculosus in vivo.

  13. Arsenic Exposure and Incidence of Type 2 Diabetes in Southwestern American Indians

    PubMed Central

    Kim, Nan Hee; Mason, Clinton C.; Nelson, Robert G.; Afton, Scott E.; Essader, Amal S.; Medlin, James E.; Levine, Keith E.; Hoppin, Jane A.; Lin, Cynthia; Knowler, William C.; Sandler, Dale P.

    2013-01-01

    Association of urinary arsenic concentration with incident diabetes was examined in American Indians from Arizona who have a high prevalence of type 2 diabetes and were screened for diabetes between 1982 and 2007. The population resides where drinking water contains arsenic at concentrations above federally recommended limits. A total of 150 nondiabetic subjects aged ≥25 years who subsequently developed type 2 diabetes were matched by year of examination and sex to 150 controls who remained nondiabetic for ≥10 years. Total urinary arsenic concentration, adjusted for urinary creatinine level, ranged from 6.6 µg/L to 123.1 µg/L, and inorganic arsenic concentration ranged from 0.1 µg/L to 36.0 µg/L. In logistic regression models adjusted for age, sex, body mass index, and urinary creatinine level, the odds ratios for incident diabetes were 1.11 (95% confidence interval (CI): 0.79, 1.57) and 1.16 (95% CI: 0.89, 1.53) for a 2-fold increase in total arsenic and inorganic arsenic, respectively. Categorical analyses suggested a positive relationship between quartiles of inorganic arsenic and incident diabetes (P = 0.056); post-hoc comparison of quartiles 2–4 with quartile 1 revealed 2-fold higher odds of diabetes in the upper quartiles (OR = 2.14, 95% CI: 1.19, 3.85). Modestly elevated exposure to inorganic arsenic may predict type 2 diabetes in American Indians. Larger studies that include measures of speciated arsenic are required for confirmation. PMID:23504692

  14. Arsenic exposure and incidence of type 2 diabetes in Southwestern American Indians.

    PubMed

    Kim, Nan Hee; Mason, Clinton C; Nelson, Robert G; Afton, Scott E; Essader, Amal S; Medlin, James E; Levine, Keith E; Hoppin, Jane A; Lin, Cynthia; Knowler, William C; Sandler, Dale P

    2013-05-01

    Association of urinary arsenic concentration with incident diabetes was examined in American Indians from Arizona who have a high prevalence of type 2 diabetes and were screened for diabetes between 1982 and 2007. The population resides where drinking water contains arsenic at concentrations above federally recommended limits. A total of 150 nondiabetic subjects aged ≥25 years who subsequently developed type 2 diabetes were matched by year of examination and sex to 150 controls who remained nondiabetic for ≥10 years. Total urinary arsenic concentration, adjusted for urinary creatinine level, ranged from 6.6 µg/L to 123.1 µg/L, and inorganic arsenic concentration ranged from 0.1 µg/L to 36.0 µg/L. In logistic regression models adjusted for age, sex, body mass index, and urinary creatinine level, the odds ratios for incident diabetes were 1.11 (95% confidence interval (CI): 0.79, 1.57) and 1.16 (95% CI: 0.89, 1.53) for a 2-fold increase in total arsenic and inorganic arsenic, respectively. Categorical analyses suggested a positive relationship between quartiles of inorganic arsenic and incident diabetes (P = 0.056); post-hoc comparison of quartiles 2-4 with quartile 1 revealed 2-fold higher odds of diabetes in the upper quartiles (OR = 2.14, 95% CI: 1.19, 3.85). Modestly elevated exposure to inorganic arsenic may predict type 2 diabetes in American Indians. Larger studies that include measures of speciated arsenic are required for confirmation.

  15. 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

  16. Identification of an arsenic resistance and arsenic-sensing system in Campylobacter jejuni.

    PubMed

    Wang, Liping; Jeon, Byeonghwa; Sahin, Orhan; Zhang, Qijing

    2009-08-01

    Arsenic is commonly present in the natural environment and is also used as a feed additive for animal production. Poultry is a major reservoir for Campylobacter jejuni, a major food-borne human pathogen causing gastroenteritis. It has been shown that Campylobacter isolates from poultry are highly resistant to arsenic compounds, but the molecular mechanisms responsible for the resistance have not been determined, and it is unclear if the acquired arsenic resistance affects the susceptibility of Campylobacter spp. to other antimicrobials. In this study, we identified a four-gene operon that contributes to arsenic resistance in Campylobacter. This operon encodes a putative membrane permease (ArsP), a transcriptional repressor (ArsR), an arsenate reductase (ArsC), and an efflux protein (Acr3). PCR analysis of various clinical C. jejuni isolates indicated a significant association of this operon with elevated resistance to arsenite and arsenate. Gene-specific mutagenesis confirmed the role of the ars operon in conferring arsenic resistance. It was further shown that this operon is subject to regulation by ArsR, which directly binds to the ars promoter and inhibits the transcription of the operon. Arsenite inhibits the binding of ArsR to the ars promoter DNA and induces the expression of the ars genes. Mutation of the ars genes did not affect the susceptibility of C. jejuni to commonly used antibiotics. These results identify the ars operon as an important mechanism for arsenic resistance and sensing in Campylobacter.

  17. Distribution of virulence genes and genotyping of CTX-M-15-producing Klebsiella pneumoniae isolated from patients with community-acquired urinary tract infection (CA-UTI).

    PubMed

    Ranjbar, Reza; Memariani, Hamed; Sorouri, Rahim; Memariani, Mojtaba

    2016-11-01

    Klebsiella pneumoniae is one of the most important agents of community-acquired urinary tract infection (CA-UTI). In addition to extended-spectrum β-lactamases (ESBLs), a number of virulence factors have been shown to play an important role in the pathogenesis of K. pneumoniae, including capsule, siderophores, and adhesins. Little is known about the genetic diversity and virulence content of the CTX-M-15-producing K. pneumoniae isolated from CA-UTI in Iran. A total of 152 K. pneumoniae isolates were collected from CA-UTI patients in Tehran from September 2015 through April 2016. Out of 152 isolates, 40 (26.3%) carried blaCTX-M-15. PCR was performed for detection of virulence genes in CTX-M-15-producing isolates. Furthermore, all of these isolates were subjected to multiple-locus variable-number of tandem repeat (VNTR) analysis (MLVA). Using MLVA method, 36 types were identified. CTX-M-15-producing K. pneumoniae isolates were grouped into 5 clonal complexes (CCs). Of these isolates, mrkD was the most prevalent virulence gene (95%), followed by kpn (60%), rmpA (37.5%), irp (35%), and magA (2.5%). No correlation between MLVA types or CCs and virulence genes or antibiotic resistance patterns was observed. Overall, it is thought that CTX-M-15-producing K. pneumoniae strains isolated from CA-UTI have arisen from different clones.

  18. 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.

  19. Response of two rice cultivars differing in their sensitivity towards arsenic, differs in their expression of glutaredoxin and glutathione S transferase genes and antioxidant usage.

    PubMed

    Dubey, Arvind Kumar; Kumar, Navin; Sahu, Nayan; Verma, Pankaj Kumar; Ranjan, Ruma; Chakrabarty, Debasis; Behera, Soumit K; Mallick, Shekhar

    2016-02-01

    Embodied study investigates the role of GRX and associated antioxidant enzymes in the detoxification mechanism between arsenic (As) sensitive (Usar-3) and tolerant cultivar (Pant Dhan 11) of Oryza sativa against As(III) and As(V), under GSH enriched, and GSH deprived conditions. The overall growth and physiological parameters in sensitive cultivar were lower than the tolerant cultivar, against various treatments of As(III) and As(V). The As accumulation in sensitive cv. against both As(III) and As(V) was lower than the corresponding treatments in tolerant cv. However, the As translocation against As(V) was lower (35% and 64%, resp.) than that of As(III), in both the cultivars. In sensitive cv. translocation of Zn and Cu was influenced by both As(V) and As(III) whereas, in tolerant cv. the translocation of Cu, Mn and Zn was influenced only by As(III). Translocation of Fe was negatively influenced by translocation of As in sensitive cv. and positively in tolerant cv. Strong correlation between H2O2, SOD, GRX, GR, GST and GSH/GSSG in sensitive cv. and between DHAR, APX, MDHAR and AsA in tolerant cv. demonstrates the underlying preference of GSH as electron donor for detoxification of H2O2 in sensitive cv. and AsA in tolerant cv. Higher expression of the four GRX and two GST genes in the sensitive cv. than tolerant cv, suggests that under As stress, GRX are synthesized more in the sensitive cv. than tolerant cv. Also, the expression of four GRX genes were higher against As(V) than As(III). The higher As accumulation in the tolerant cv. is due to lower GST expression, is attributed to the absence of thiolation and sequestration of As in roots, the translocation of As to shoots is higher.

  20. Arsenic: homicidal intoxication

    SciTech Connect

    Massey, E.W.; Wold, D.; Heyman, A.

    1984-07-01

    Arsenic-induced deaths have been known to occur from accidental poisoning, as a result of medical therapy, and from intentional poisonings in homicide and suicide. Twenty-eight arsenic deaths in North Carolina from 1972 to 1982 included 14 homicides and seven suicides. In addition, 56 hospitalized victims of arsenic poisoning were identified at Duke Medical Center from 1970 to 1980. Four case histories of arsenic poisoning in North Carolina are presented and clinical manifestations are discussed. In view of the continued widespread use of arsenic in industry and agriculture, and its ubiquity in the environment, arsenic poisoning will continue to occur. A need for knowledge of its toxicity and of the clinical manifestations of acute and chronic arsenic poisoning will also continue.

  1. Arsenic geochemistry and health.

    PubMed

    Duker, Alfred A; Carranza, E J M; Hale, Martin

    2005-07-01

    Arsenic occurs naturally in the earth's crust and is widely distributed in the environment. Natural mineralization and activities of microorganisms enhance arsenic mobilization in the environment but human intervention has exacerbated arsenic contamination. Although arsenic is useful for industrial, agricultural, medicinal and other purposes, it exerts a toxic effect in a variety of organisms, including humans. Arsenic exposure may not only affect and disable organs of the body, especially the skin, but may also interfere with the proper functioning of the immune system. This paper, therefore, generally highlights the toxic effects of arsenic as well as its mobilization in the natural environment and possible controls. It also briefly attempts to outline the impact of arsenic on the immune system, whose alteration could lead to viral/bacterial infections.

  2. Arsenic removal from water

    DOEpatents

    Moore, Robert C.; Anderson, D. Richard

    2007-07-24

    Methods for removing arsenic from water by addition of inexpensive and commonly available magnesium oxide, magnesium hydroxide, calcium oxide, or calcium hydroxide to the water. The hydroxide has a strong chemical affinity for arsenic and rapidly adsorbs arsenic, even in the presence of carbonate in the water. Simple and commercially available mechanical methods for removal of magnesium hydroxide particles with adsorbed arsenic from drinking water can be used, including filtration, dissolved air flotation, vortex separation, or centrifugal separation. A method for continuous removal of arsenic from water is provided. Also provided is a method for concentrating arsenic in a water sample to facilitate quantification of arsenic, by means of magnesium or calcium hydroxide adsorption.

  3. The metabolism of inorganic arsenic oxides, gallium arsenide, and arsine: a toxicochemical review.

    PubMed

    Carter, Dean E; Aposhian, H Vasken; Gandolfi, A Jay

    2003-12-15

    The aim of this review is to compare the metabolism, chemistry, and biological effects to determine if either of the industrial arsenicals (arsine and gallium arsenide) act like the environmental arsenic oxides (arsenite and arsenate). The metabolism of the arsenic oxides has been extensively investigated in the past 4 years and the differences between the arsenic metabolites in the oxidation states +III versus +V and with one or two methyl groups added have shown increased importance. The arsenic oxide metabolism has been compared with arsine (oxidation state -III) and arsenide (oxidation state between 0 to -III). The different metabolites appear to have different strengths of reaction for binding arsenic (III) to thiol groups, their oxidation-reduction reactions and their forming an arsenic-carbon bond. It is unclear if the differences in parameters such as the presence or absence of methyl metabolites, the rates of AsV reduction compared to the rates of AsIII oxidation, or the competition of phosphate and arsenate for cellular uptake are large enough to change biological effects. The arsine rate of decomposition, products of metabolism, target organ of toxic action, and protein binding appeared to support an oxidized arsenic metabolite. This arsine metabolite was very different from anything made by the arsenic oxides. The gallium arsenide had a lower solubility than any other arsenic compound and it had a disproportionate intensity of lung damage to suggest that the GaAs had a site of contact interaction and that oxidation reactions were important in its toxicity. The urinary metabolites after GaAs exposure were the same as excreted by arsenic oxides but the chemical compounds responsible for the toxic effects of GaAs are different from the arsenic oxides. The review concludes that there is insufficient evidence to equate the different arsenic compounds. There are several differences in the toxicity of the arsenic compounds that will require substantial

  4. Linking microbial oxidation of arsenic with detection and phylogenetic analysis of arsenite oxidase genes in diverse geothermal environments.

    PubMed

    Hamamura, N; Macur, R E; Korf, S; Ackerman, G; Taylor, W P; Kozubal, M; Reysenbach, A-L; Inskeep, W P

    2009-02-01

    The identification and characterization of genes involved in the microbial oxidation of arsenite will contribute to our understanding of factors controlling As cycling in natural systems. Towards this goal, we recently characterized the widespread occurrence of aerobic arsenite oxidase genes (aroA-like) from pure-culture bacterial isolates, soils, sediments and geothermal mats, but were unable to detect these genes in all geothermal systems where we have observed microbial arsenite oxidation. Consequently, the objectives of the current study were to measure arsenite-oxidation rates in geochemically diverse thermal habitats in Yellowstone National Park (YNP) ranging in pH from 2.6 to 8, and to identify corresponding 16S rRNA and aroA genotypes associated with these arsenite-oxidizing environments. Geochemical analyses, including measurement of arsenite-oxidation rates within geothermal outflow channels, were combined with 16S rRNA gene and aroA functional gene analysis using newly designed primers to capture previously undescribed aroA-like arsenite oxidase gene diversity. The majority of bacterial 16S rRNA gene sequences found in acidic (pH 2.6-3.6) Fe-oxyhydroxide microbial mats were closely related to Hydrogenobaculum spp. (members of the bacterial order Aquificales), while the predominant sequences from near-neutral (pH 6.2-8) springs were affiliated with other Aquificales including Sulfurihydrogenibium spp., Thermocrinis spp. and Hydrogenobacter spp., as well as members of the Deinococci, Thermodesulfobacteria and beta-Proteobacteria. Modified primers designed around previously characterized and newly identified aroA-like genes successfully amplified new lineages of aroA-like genes associated with members of the Aquificales across all geothermal systems examined. The expression of Aquificales aroA-like genes was also confirmed in situ, and the resultant cDNA sequences were consistent with aroA genotypes identified in the same environments. The aroA sequences

  5. Placental arsenic concentrations in relation to both maternal and infant biomarkers of exposure in a US cohort

    PubMed Central

    Punshon, Tracy; Davis, Matthew A.; Marsit, Carmen J.; Theiler, Shaleen K.; Baker, Emily R.; Jackson Brian, P.; Conway, David C.; Karagas, Margaret R.

    2015-01-01

    Arsenic crosses the placenta and may have adverse consequences in utero and later in life. At present, little is known about arsenic concentrations in placenta and their relation to maternal and infant exposures particularly at common levels of exposure. We measured placenta arsenic in a US cohort potentially exposed via drinking water from private wells, and evaluated the relationships between placenta and maternal and infant biomarker arsenic concentrations. We measured total arsenic concentrations in placental samples from women enrolled in the New Hampshire Birth Cohort Study (N=766). We compared these data to maternal urinary arsenic (total arsenic and individual species) collected at approximately 24–28 week gestation, along with maternal post-partum toenails and infant toenails using non-parametric multivariate analysis of log10-transformed data. We also examined the association between placental arsenic and household drinking water arsenic. Placenta arsenic concentrations were related to arsenic concentrations in maternal urine (β 0.55, P value <0.0001), maternal (β 0.30, P value 0.0196) and infant toenails (β 0.40, P value 0.0293) and household drinking water (β 0.09, P value <0.0001). Thus, our data suggest that placenta arsenic concentrations reflect both maternal and infant exposures. PMID:25805251

  6. Genetic susceptibility to renal scar formation after urinary tract infection: a systematic review and meta-analysis of candidate gene polymorphisms.

    PubMed

    Zaffanello, Marco; Tardivo, Stefano; Cataldi, Luigi; Fanos, Vassilios; Biban, Paolo; Malerba, Giovanni

    2011-07-01

    Identifying patients who may develop renal scarring after urinary tract infections (UTI) remains challenging, as clinical determinants explain only a portion of individual risk. An additional factor that likely affects risk is individual genetic variability. We searched for peer-reviewed articles from 1980 to December 2009 in electronic databases that reported results showing an association between gene polymorphims and renal scaring after UTI. Two independent researchers screened articles using predetermined criteria. Studies were assessed for methodological quality using an aggregate scoring system. The 18 studies ultimately included in the review had investigated 16 polymorphisms in nine genes in association with renal scarring formation after UTI. Based on the predetermined criteria for assessing the quality of the studies, 12 studies (67%) were identified as being of poor quality design. A meta-analysis of cumulative studies showed on association between renal scarring formation after UTI and the angiotensin converting enzyme insertion/deletion polymorphism [ACE I/D; recessive model for D allele; odds ratio (OR) 1.73, 95% confidence interval (CI) 1.09-2.74, P = 0.02] or transforming growth factor (TGF)-β1 c.-509 T > C polymorphism (dominant model for T allele; OR 2.24, 95% CI 1.34-3.76, P = 0.002). However, heterogeneity among studies was large, indicating a strong difference that cannot only be explained by differences in study design. The studies reviewed in this article support a modest involvement of the vasomotor and inflammatory genes in the development of renal scarring after UTIs. This review also shows that only few possible candidate genes have been investigated for an association with renal scarring, raising the hypothesis that some gene polymorphisms may exert their effects through an interaction with as yet uninvestigated factors that may be related to geographic and/or socio-economic differences.

  7. Comparative Genomics Analysis of a New Exiguobacterium Strain from Salar de Huasco Reveals a Repertoire of Stress-Related Genes and Arsenic Resistance

    PubMed Central

    Castro-Severyn, Juan; Remonsellez, Francisco; Valenzuela, Sandro L.; Salinas, Cesar; Fortt, Jonathan; Aguilar, Pablo; Pardo-Esté, Coral; Dorador, Cristina; Quatrini, Raquel; Molina, Franck; Aguayo, Daniel; Castro-Nallar, Eduardo; Saavedra, Claudia P.

    2017-01-01

    The Atacama Desert hosts diverse ecosystems including salt flats and shallow Andean lakes. Several heavy metals are found in the Atacama Desert, and microorganisms growing in this environment show varying levels of resistance/tolerance to copper, tellurium, and arsenic, among others. Herein, we report the genome sequence and comparative genomic analysis of a new Exiguobacterium strain, sp. SH31, isolated from an altiplanic shallow athalassohaline lake. Exiguobacterium sp. SH31 belongs to the phylogenetic Group II and its closest relative is Exiguobacterium sp. S17, isolated from the Argentinian Altiplano (95% average nucleotide identity). Strain SH31 encodes a wide repertoire of proteins required for cadmium, copper, mercury, tellurium, chromium, and arsenic resistance. Of the 34 Exiguobacterium genomes that were inspected, only isolates SH31 and S17 encode the arsenic efflux pump Acr3. Strain SH31 was able to grow in up to 10 mM arsenite and 100 mM arsenate, indicating that it is arsenic resistant. Further, expression of the ars operon and acr3 was strongly induced in response to both toxics, suggesting that the arsenic efflux pump Acr3 mediates arsenic resistance in Exiguobacterium sp. SH31. PMID:28377753

  8. Comparative Genomics Analysis of a New Exiguobacterium Strain from Salar de Huasco Reveals a Repertoire of Stress-Related Genes and Arsenic Resistance.

    PubMed

    Castro-Severyn, Juan; Remonsellez, Francisco; Valenzuela, Sandro L; Salinas, Cesar; Fortt, Jonathan; Aguilar, Pablo; Pardo-Esté, Coral; Dorador, Cristina; Quatrini, Raquel; Molina, Franck; Aguayo, Daniel; Castro-Nallar, Eduardo; Saavedra, Claudia P

    2017-01-01

    The Atacama Desert hosts diverse ecosystems including salt flats and shallow Andean lakes. Several heavy metals are found in the Atacama Desert, and microorganisms growing in this environment show varying levels of resistance/tolerance to copper, tellurium, and arsenic, among others. Herein, we report the genome sequence and comparative genomic analysis of a new Exiguobacterium strain, sp. SH31, isolated from an altiplanic shallow athalassohaline lake. Exiguobacterium sp. SH31 belongs to the phylogenetic Group II and its closest relative is Exiguobacterium sp. S17, isolated from the Argentinian Altiplano (95% average nucleotide identity). Strain SH31 encodes a wide repertoire of proteins required for cadmium, copper, mercury, tellurium, chromium, and arsenic resistance. Of the 34 Exiguobacterium genomes that were inspected, only isolates SH31 and S17 encode the arsenic efflux pump Acr3. Strain SH31 was able to grow in up to 10 mM arsenite and 100 mM arsenate, indicating that it is arsenic resistant. Further, expression of the ars operon and acr3 was strongly induced in response to both toxics, suggesting that the arsenic efflux pump Acr3 mediates arsenic resistance in Exiguobacterium sp. SH31.

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

    SciTech Connect

    Gomez-Rubio, Paulina; Roberge, Jason; Arendell, Leslie; Harris, Robin B.; O'Rourke, Mary K.; Chen, Zhao; Cantu-Soto, Ernesto; Meza-Montenegro, Maria M.; Billheimer, Dean; Lu Zhenqiang; Klimecki, Walter T.

    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 the 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.

  10. Microarray analysis revealed dysregulation of multiple genes associated with chemoresistance to As(2)O(3) and increased tumor aggressiveness in a newly established arsenic-resistant ovarian cancer cell line, OVCAR-3/AsR.

    PubMed

    Ong, Pei-Shi; Chan, Sui-Yung; Ho, Paul C

    2012-02-14

    The potential of arsenic trioxide (As(2)O(3)) for use as a novel therapy for ovarian cancer treatment has been increasingly recognized. In this study, we developed an arsenic-resistant OVCAR-3 subline (OVCAR-3/AsR) and aimed to identify the molecular mechanisms and signaling pathways contributing to the development of acquired arsenic chemoresistance in ovarian cancer. OVCAR-3/AsR cells were obtained following continual exposure of parental OVCAR-3 cells to low dose As(2)O(3) for 12months. Cytotoxicity of OVCAR-3/AsR cells to As(2)O(3), paclitaxel and cisplatin was investigated. Cell apoptosis and cell cycle distribution following As(2)O(3) treatment of OVCAR-3/AsR cells was also analyzed using flow cytometry. Subsequently, cDNA microarray analysis was performed from the RNA samples of OVCAR-3 and OVCAR-3/AsR cells in duplicate experiments. Microarray data were analyzed using Genespring® and Pathway Studio® Softwares. OVCAR-3/AsR cells showed 9-fold greater resistance to As(2)O(3) and lack of collateral resistance to cisplatin and paclitaxel. Compared with parental OVCAR-3 cells, OVCAR-3/AsR had significantly lower apoptotic rates following As(2)O(3) treatment. These cells were also arrested at both the S phase and G(2)/M phase of the cell cycle after exposure to high concentrations of As(2)O(3). Gene expression profiling revealed significant differences in expression levels of 397 genes between OVCAR-3/AsR and OVCAR-3 cells. The differentially regulated transcripts genes have functional ontologies related to continued cancer cell growth, cell survival, tumor metastasis and tumor aggressiveness. Additionally, numerous gene targets of the nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor showed elevated expression in OVCAR-3/AsR cells. Subsequent pathway analysis further revealed a gene network involving interleukin 1-alpha (IL1A) in mediating the arsenic-resistant phenotype. These results showed that changes in multiple genes and an

  11. ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE AND THE METHYLATION OF ARSENICALS

    EPA Science Inventory

    Metabolic conversion of inorganic arsenic into methylated products is a multistep process that yields mono, di, and trimethylated arsenicals. In recent years, it has become apparent that formation of methylated metabolites of inorganic arsenic is not necessarily a detoxification...

  12. Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer

    PubMed Central

    Ceylan, Gülay Güleç; Önalan, Ebru Etem; Kuloğlu, Tuncay; Aydoğ, Gülten; Keleş, İbrahim; Tonyali, Şenol; Ceylan, Cavit

    2016-01-01

    Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer. PMID:28101241

  13. Arsenic-induced bladder cancer in an animal model

    SciTech Connect

    Cohen, Samuel M. Ohnishi, Takamasa Arnold, Lora L. Le, X. Chris

    2007-08-01

    Dimethylarsinic acid (DMA{sup V}) is carcinogenic to the rat urinary bladder, but not in mice. The carcinogenic mode of action involves cytotoxicity followed by regenerative cell proliferation. Dietary DMA{sup V} does not produce urinary solids or significant alterations in urinary composition. The cytotoxicity is due to formation of a reactive metabolite, likely dimethylarsinous acid (DMA{sup III}), concentrated and excreted in the urine. Urinary concentrations of DMA{sup III} are dose-dependent, and the urinary concentrations are at cytotoxic levels based on in vitro studies. The no observed effect level (NOEL) in these rat dietary studies for detectable levels of DMA{sup III}, cytotoxicity, and proliferation is 2 ppm, with marginal changes at 10 ppm. The tumorigenic dose is 100 ppm. Recent investigations have demonstrated that arsenicals administered to the rat result in binding to a specific cysteine in the hemoglobin alpha chain as DMA{sup III}, regardless of the arsenical being administered. Monomethylarsonic acid (MMA{sup V}) is not carcinogenic in rats or mice. In short term experiments ({<=} 10 weeks), sodium arsenate in the drinking water induces significant cytotoxicity and regenerative proliferation. There is little evidence that the cytotoxicity produced following administration of arsenicals is caused by oxidative damage, as antioxidants show little inhibitory activity of the cytotoxicity of the various arsenicals either in vitro or in vivo. In summary, the mode of action for DMA{sup V}-induced bladder carcinogenesis in the rat involves generation of a reactive metabolite (DMA{sup III}) leading to cytotoxicity and regenerative proliferation, is a non-linear process, and likely involves a threshold. Extrapolation to human risk needs to take this into account along with the significant differences in toxicokinetics and toxicodynamics that occur between different species.

  14. 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.

  15. A new genome scan for primary nonsyndromic vesicoureteric reflux emphasizes high genetic heterogeneity and shows linkage and association with various genes already implicated in urinary tract development

    PubMed Central

    Darlow, J M; Dobson, M G; Darlay, R; Molony, C M; Hunziker, M; Green, A J; Cordell, H J; Puri, P; Barton, D E

    2014-01-01

    Primary vesicoureteric reflux (VUR), the retrograde flow of urine from the bladder toward the kidneys, results from a developmental anomaly of the vesicoureteric valve mechanism, and is often associated with other urinary tract anomalies. It is the most common urological problem in children, with an estimated prevalence of 1–2%, and is a major cause of hypertension in childhood and of renal failure in childhood or adult life. We present the results of a genetic linkage and association scan using 900,000 markers. Our linkage results show a large number of suggestive linkage peaks, with different results in two groups of families, suggesting that VUR is even more genetically heterogeneous than previously imagined. The only marker achieving P < 0.02 for linkage in both groups of families is 270 kb from EMX2. In three sibships, we found recessive linkage to KHDRBS3, previously reported in a Somali family. In another family we discovered sex-reversal associated with VUR, implicating PRKX, for which there was weak support for dominant linkage in the overall data set. Several other candidate genes are suggested by our linkage or association results, and four of our linkage peaks are within copy-number variants recently found to be associated with renal hypodysplasia. Undoubtedly there are many genes related to VUR. Our study gives support to some loci suggested by earlier studies as well as suggesting new ones, and provides numerous indications for further investigations. PMID:24498626

  16. Effect of CD44 gene polymorphisms on risk of transitional cell carcinoma of the urinary bladder in Taiwan.

    PubMed

    Weng, Wei-Chun; Huang, Yu-Hui; Yang, Shun-Fa; Wang, Shian-Shiang; Kuo, Wu-Hsien; Hsueh, Chao-Wen; Huang, Ching-Hsuan; Chou, Ying-Erh

    2016-05-01

    The carcinogenesis of transitional cell carcinoma (TCC) of the urinary bladder involves etiological factors, such as ethnicity, the environment, genetics, and diet. Cluster of differentiation (CD44), a well-known tumor marker, plays a crucial role in regulating tumor cell differentiation and metastasis. This study investigated the effect of CD44 single nucleotide polymorphisms (SNPs) on TCC risk and clinicopathological characteristics. Five SNPs of CD44 were analyzed through real-time polymerase chain reaction in 275 patients with TCC and 275 participants without cancer. In this study, we observed that CD44 rs187115 polymorphism carriers with the genotype of at least one G were associated with TCC risk. Furthermore, TCC patients who carried at least one G allele at CD44 rs187115 had a higher stage risk than did patients carrying the wild-type allele (p < 0.05). In addition, The AATAC or GACGC haplotype among the five CD44 sites was also associated with a reduced risk of TCC. In conclusion, our results suggest that CD44 SNPs influence the risk of TCC. Patients with CD44 rs187115 variant genotypes (AG + GG) exhibited a higher risk of TCC; these patients may possess chemoresistance to developing late-stage TCC compared with those with the wild-type genotype. The CD44 rs187115 SNP may predict poor prognosis in patients with TCC.

  17. Gene Expression Changes in Human Lung Cells Exposed to Arsenic, Chromium, Nickel or Vanadium Indicate the First Steps in Cancer

    PubMed Central

    Clancy, Hailey A.; Sun, Hong; Passantino, Lisa; Kluz, Thomas; Muñoz, Alexandra; Zavadil, Jiri; Costa, Max

    2013-01-01

    The complex process of carcinogenesis begins with transformation of a single cell to favor aberrant traits such as loss of contact inhibition and unregulated proliferation – features found in every cancer. Despite cancer’s widespread prevalence, the early events that initiate cancer remain elusive, and without knowledge of these events cancer prevention is difficult. Here we show that exposure to As, Cr, Ni, or Vanadium (V) promotes changes in gene expression that occur in conjunction with aberrant growth. We exposed immortalized human bronchial epithelial cells to one of four metals/metalloid for four to eight weeks and selected transformed clonal populations based upon anchorage independent growth of single cells in soft agar. We detected a metal-specific footprint of cancer-related gene expression that was consistent across multiple transformed clones. These gene expression changes persisted in the absence of the progenitor metal for numerous cell divisions. Our results show that even a brief exposure to a carcinogenic metal may cause many changes in gene expression in the exposed cells, and that from these many changes, the specific change(s) that each metal causes that initiate cancer likely arise. PMID:22714537

  18. Genetic Variation in Arsenic (+3 Oxidation State) Methyltransferase (AS3MT), Arsenic Metabolism and Risk of Basal Cell Carcinoma in a European Population

    PubMed Central

    Engström, Karin S; Vahter, Marie; Fletcher, Tony; Leonardi, Giovanni; Goessler, Walter; Gurzau, Eugen; Koppova, Kvetoslava; Rudnai, Peter; Kumar, Rajiv; Broberg, Karin

    2015-01-01

    Exposure to inorganic arsenic increases the risk of basal cell carcinoma (BCC). Arsenic metabolism is a susceptibility factor for arsenic toxicity, and specific haplotypes in arsenic (+3 oxidation state) methyltransferase (AS3MT) have been associated with increased urinary fractions of the most toxic arsenic metabolite, methylarsonic acid (MMA). The aim of this study is to elucidate the association of AS3MT haplotypes with arsenic metabolism and the risk of BCC. Four AS3MT polymorphisms were genotyped in BCC cases (N = 529) and controls (N = 533) from Eastern Europe with low to moderate arsenic exposure (lifetime average drinking water concentration: 1.3 µg/L, range 0.01–167 µg/L). Urinary metabolites [inorganic arsenic (iAs), MMA, dimethylarsinic acid (DMA)] were analyzed by HPLC-ICPMS. Five AS3MT haplotypes (based on rs3740400 A/C, rs3740393 G/C, rs11191439 T/C and rs1046778 T/C) had frequencies >5%. Individuals with the CCTC haplotype had lower %iAs (P = 0.032) and %MMA (P = 0.020) in urine, and higher %DMA (P = 0.033); individuals with the CGCT haplotype had higher %MMA (P < 0.001) and lower %DMA (P < 0.001). All haplotypes showed increased risk of BCC with increasing arsenic exposure through drinking water (ORs 1.1–1.4, P values from <0.001 to 0.082), except for the CCTC haplotype (OR 1.0, CI 0.9–1.2, P value 0.85). The results suggest that carriage of AS3MT haplotypes associated with less-efficient arsenic methylation, or lack of AS3MT haplotypes associated with a more-efficient arsenic methylation, results in higher risk of arsenic-related BCC. The fact that AS3MT haplotype status modified arsenic metabolism, and in turn the arsenic-related BCC risk, supports a causal relationship between low-level arsenic exposure and BCC. Environ. Mol. Mutagen. 56:60–69, 2015. © 2014 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society PMID:25156000

  19. 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...

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

    SciTech Connect

    Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Victor H.; Contreras-Ruiz, Jose; Garcia-Vargas, Gonzalo G.; Razo, Luz M. del

    2007-08-01

    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-{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) 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-{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.

  1. Environmental arsenic exposure and microbiota in induced sputum.

    PubMed

    White, Allison G; Watts, George S; Lu, Zhenqiang; Meza-Montenegro, Maria M; Lutz, Eric A; Harber, Philip; Burgess, Jefferey L

    2014-02-21

    Arsenic exposure from drinking water is associated with adverse respiratory outcomes, but it is unknown whether arsenic affects pulmonary microbiota. This exploratory study assessed the effect of exposure to arsenic in drinking water on bacterial diversity in the respiratory tract of non-smokers. Induced sputum was collected from 10 subjects with moderate mean household water arsenic concentration (21.1 ± 6.4 ppb) and 10 subjects with low household water arsenic (2.4 ± 0.8 ppb). To assess microbiota in sputum, the V6 hypervariable region amplicons of bacterial 16s rRNA genes were sequenced using the Ion Torrent Personal Genome Machine. Microbial community differences between arsenic exposure groups were evaluated using QIIME and Metastats. A total of 3,920,441 sequence reads, ranging from 37,935 to 508,787 per sample for 316 chips after QIIME quality filtering, were taxonomically classified into 142 individual genera and five phyla. Firmicutes (22%), Proteobacteria (17%) and Bacteriodetes (12%) were the main phyla in all samples, with Neisseriaceae (15%), Prevotellaceae (12%) and Veillonellacea (7%) being most common at the genus level. Some genera, including Gemella, Lactobacillales, Streptococcus, Neisseria and Pasteurellaceae were elevated in the moderate arsenic exposure group, while Rothia, Prevotella, Prevotellaceae Fusobacterium and Neisseriaceae were decreased, although none of these differences was statistically significant. Future studies with more participants and a greater range of arsenic exposure are needed to further elucidate the effects of drinking water arsenic consumption on respiratory microbiota.

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

    PubMed Central

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

    2017-01-01

    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. PMID:28303940

  3. 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.

  4. 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

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

    2015-03-31

    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.

  5. Resistance mechanisms to arsenicals and antimonials.

    PubMed

    Rosen, B P

    1995-01-01

    Salts and organic derivatives of arsenic and antimony are quite toxic. Living organisms have adapted to this toxicity by the evolution of resistance mechanisms. Both prokaryotic and eukaryotic cells develop resistance when exposed to arsenicals or antimonials. In the case of bacteria resistance is conferred by plasmid-encoded arsenical resistance (ars) operons. The genes and gene products of the ars operon of the clinically-isolated conjugative R-factor R773 have been identified and their mechanism of action elucidated. The operon encodes an ATP-driven pump that extrudes arsenite and antimonite from the cells. The lowering of their intracellular concentration results in resistance. Arsenate resistance results from the action of the plasmid-encoded arsenate reductase that reduces arsenate to arsenite, which is then pumped out of the cell.

  6. Arsenic-Induced Pancreatitis

    PubMed Central

    Connelly, Sean; Zancosky, Krysia; Farah, Katie

    2011-01-01

    The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide has brought about tremendous advancement in the treatment of acute promyelocytic myelogenous leukemia (APML). In most instances, the benefits of these treatments outweigh the risks associated with their respective safety profiles. Although acute pancreatitis is not commonly associated with arsenic toxicity, it should be considered as a possible side effect. We report a case of arsenic-induced pancreatitis in a patient with APML. PMID:22606427

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

    SciTech Connect

    Huang, Y.-K.; Tseng, C.-H.; Huang, Y.-L.; Yang, M.-H.; Chen, C.-J.; Hsueh, Y.-M. . E-mail: ymhsueh@tmu.edu.tw

    2007-01-15

    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 generator 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.

  8. AB283. SPR-10 Down-regulation of ryanodine receptor gene expression in murine urinary bladder smooth muscle following partial bladder outlet obstruction

    PubMed Central

    Boopathi, Ettickan; Javed, Elham; Addya, Shankar; Fortina, Paolo; Zderic, Stephen; Wein, Alan; Chacko, Samuel

    2016-01-01

    Objective Urinary bladder smooth muscle (UBSM) displays spontaneous action potentials and this potential is related to the phasic nature of spontaneous contractions in this tissue. The amplitude of a phasic contraction depends on the increase in Ca2+ entry caused by membrane depolarization. Ryanodine receptors (RyRs) in UBSM decreases the force production by decreasing the frequency of phasic contractions through interactions with large-conductance Ca2+-activated K+ (BK) and small-conductance Ca2+-activated K+ (SK) channels. Microarray and network analysis were employed to determine the changes in mRNA in 14-day obstructed murine bladders. We found that obstruction significantly down-regulated the RyRs in bladder smooth muscle (BSM). Methods Male C57Bl/6 mice were surgically obstructed and kept for 14 days. Sham-operated mice served as a control. Bladders were excised; urothelium scraped off with a scalpel, and the serosa was removed. BSM obtained from PBOO and sham control animals were used for microarray and western blotting Results Pathway-based analysis of these gene signatures showed significant number of under-expressed genes in obstructed bladder and they were mapped to proteins involved in calcium signaling. We focused our work on RyR protein expression in BSM. There was a four-fold reduction of RyR3 in BSM in 14-day obstructed groups as shown by microarray and immunoblotting compared to that of sham-operated animals. Conclusions These results confirm that the RyR gene expression is down-regulated in obstructed murine bladder smooth muscle. Funding Source(s) None

  9. Influence of night-shift and napping at work on urinary melatonin, 17-β-estradiol and clock gene expression in pre-menopausal nurses.

    PubMed

    Bracci, M; Copertaro, A; Manzella, N; Staffolani, S; Strafella, E; Nocchi, L; Barbaresi, M; Copertaro, B; Rapisarda, V; Valentino, M; Santarelli, L

    2013-01-01

    Night-workers experience disruption of the sleep-wake cycle and light at night which may increase breast cancer risk by suppressing the nocturnal melatonin surge, resulting in higher levels of circulating estrogens. Night-work may also deregulate peripheral clock genes which have been found to be altered in breast cancer. This study investigated urinary 6-sulfatoxymelatonin (aMT6s), serum 17-beta-estradiol levels in premenopausal shift nurses at the end of the night-shift compared to a control group of daytime nurses. Peripheral clock gene expression in lymphocytes were also investigated. All participants were sampled in the follicular phase of the menstrual cycle. The effect of nurses’ ability to take a short nap during the night-shift was also explored. The shift-work group had significantly lower aMT6s levels than daytime nurses independently of a nap. Night-shift napping significantly influences 17-beta-estradiol levels resulting in higher outcomes in nurses who do not take a nap compared to napping group and daytime workers. Peripheral clock genes expression investigated was not significantly different among the groups. Our findings suggest that shift nurses experience changes in aMT6s levels after a night-shift. Napping habits influence 17-beta-estradiol levels at the end of a night-shift. These findings might be related to the increased cancer risk reported in night-shift workers and suggest that a short nap during night-shifts may exert a positive effect.

  10. Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression

    PubMed Central

    Zhao, Christopher Q.; Young, Matthew R.; Diwan, Bhalchandra A.; Coogan, Timothy P.; Waalkes, Michael P.

    1997-01-01

    Inorganic arsenic, a human carcinogen, is enzymatically methylated for detoxication, consuming S-adenosyl-methionine (SAM) in the process. The fact that DNA methyltransferases (MeTases) require this same methyl donor suggests a role for methylation in arsenic carcinogenesis. Here we test the hypothesis that arsenic-induced initiation results from DNA hypomethylation caused by continuous methyl depletion. The hypothesis was tested by first inducing transformation in a rat liver epithelial cell line by chronic exposure to low levels of arsenic, as confirmed by the development of highly aggressive, malignant tumors after inoculation of cells into Nude mice. Global DNA hypomethylation occurred concurrently with malignant transformation and in the presence of depressed levels of S-adenosyl-methionine. Arsenic-induced DNA hypomethylation was a function of dose and exposure duration, and remained constant even after withdrawal of arsenic. Hyperexpressibility of the MT gene, a gene for which expression is clearly controlled by DNA methylation, was also detected in transformed cells. Acute arsenic or arsenic at nontransforming levels did not induce global hypomethylation of DNA. Whereas transcription of DNA MeTase was elevated, the MeTase enzymatic activity was reduced with arsenic transformation. Taken together, these results indicate arsenic can act as a carcinogen by inducing DNA hypomethylation, which in turn facilitates aberrant gene expression, and they constitute a tenable theory of mechanism in arsenic carcinogenesis. PMID:9380733

  11. Arsenic and fluoride co-exposure affects the expression of apoptotic and inflammatory genes and proteins in mononuclear cells from children.

    PubMed

    Estrada-Capetillo, B L; Ortiz-Pérez, M D; Salgado-Bustamante, M; Calderón-Aranda, E; Rodríguez-Pinal, C J; Reynaga-Hernández, E; Corral-Fernández, N E; González-Amaro, R; Portales-Pérez, D P

    2014-02-01

    Humans may be exposed to arsenic (As) and fluoride (F) through water consumption. However, the interaction between these two elements and gene expression in apoptosis or inflammatory processes in children has not been thoroughly investigated. Herein, the expression of cIAP-1, XIAP, TNF-α, ENA-78, survivin, CD25, and CD40 was evaluated by RT-PCR. Additionally, the surface expression of CD25, CD40, and CD40L on peripheral blood mononuclear cells was analyzed by flow cytometry, and TNF-α was measured by Western blotting. This study examined 72 children aged 6-12 years who were chronically exposed to As (154.2μg/L) and F (5.3mg/L) in drinking water and in food cooked with the same water. The urine concentrations of As (6.9-122.4μg/L) were positively correlated with the urine concentrations of F (1.0-8.8mg/L) (r(2)=0.413, p<0.0001). The CD25 gene expression levels and urine concentrations of As and F were negatively correlated, though the CD40 expression levels were negatively correlated only with the As concentration. Age and height influenced the expression of cIAP-1, whereas XIAP expression was correlated only with age. Additionally, there was a lower percentage of CD25- and CD40-positive cells in the group of 6- to 8-year-old children exposed to the highest concentrations of both As and F when compared to the 9- to 12-year-old group (CD25: 0.7±0.8 vs. 1.1±0.9, p<0.0014; CD40: 16.0±7.0 vs. 21.8±5.8, p<0.0003). PHA-stimulated lymphocytes did not show any changes in the induction of CD25, CD69, or CD95. In summary, high concentrations of As and F alter the expression patterns of CD25 and CD40 at both the genetic and protein levels. These changes could decrease immune responses in children exposed to As and F.

  12. Oxidative Damage in Lymphocytes of Copper Smelter Workers Correlated to Higher Levels of Excreted Arsenic

    PubMed Central

    Escobar, Jorge; Varela-Nallar, Lorena; Coddou, Claudio; Nelson, Pablo; Maisey, Kevin; Valdés, Daniel; Aspee, Alexis; Espinosa, Victoria; Rozas, Carlos; Montoya, Margarita; Mandiola, Cristian; Rodríguez, Felipe E.; Acuña-Castillo, Claudio; Escobar, Alejandro; Fernández, Ricardo; Diaz, Hernán; Sandoval, Mario; Imarai, Mónica; Rios, Miguel

    2010-01-01

    Arsenic has been associated with multiple harmful effects at the cellular level. Indirectly these defects could be related to impairment of the integrity of the immune system, in particular in lymphoid population. To characterize the effect of Arsenic on redox status on this population, copper smelter workers and arsenic unexposed donors were recruited for this study. We analyzed urine samples and lymphocyte enriched fractions from donors to determinate arsenic levels and lymphocyte proliferation. Moreover, we studied the presence of oxidative markers MDA, vitamin E and SOD activity in donor plasma. Here we demonstrated that in human beings exposed to high arsenic concentrations, lymphocyte MDA and arsenic urinary levels showed a positive correlation with SOD activity, and a negative correlation with vitamin E serum levels. Strikingly, lymphocytes from the arsenic exposed population respond to a polyclonal stimulator, phytohemaglutinin, with higher rates of thymidine incorporation than lymphocytes of a control population. As well, similar in vitro responses to arsenic were observed using a T cell line. Our results suggest that chronic human exposure to arsenic induces oxidative damage in lymphocytes and could be considered more relevant than evaluation of T cell surveillance. PMID:21253489

  13. GENE EXPRESSION PROFILING OF RESPONSES TO DIMETHYLARSINIC ACID IN FEMALE F344 RAT UROTHELIUM

    EPA Science Inventory

    Arsenic is a human carcinogen and epidemiologic evidence implicates it in the development of urinary bladder cancer. Even though several mechanisms have been proposed for arsenic carcinogenicity, the mode of action of inorganic arsenic (iAs) is confounded by the limited availabil...

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

    PubMed

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

    2013-03-01

    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 (DMAs(III)), 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 DMAs(III) 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 DMAs(III) and be more likely to develop diabetes when exposed to arsenic.

  15. Glutathione Modulates Recominant Rat Arsenic (+3 Oxidation State) Methyltransferase-Catalyzed Formation of Trimethylarsine Oxide and Trimethylarsine

    EPA Science Inventory

    Humans and other species enzymatically convert inorganic arsenic (iAs) into methylated metabolites. Although the major metabolites are mono- and dimethylated arsenicals, trimethylated arsenicals have been detected in urine following exposure to iAs. The AS3MT gene encodes an ars...

  16. Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis

    EPA Science Inventory

    The biotransformation of inorganic arsenic (iAs) involves methylation by an arsenic (+3 oxidation state) methyltransferase (AS3MT), yielding methyl arsenic (MA), dimethyl arsenic (DMA), and trimethylarsenic (TMA). To identify molecular mechanisms that coordinate arsenic biotra...

  17. Arsenic activation neutron detector

    DOEpatents

    Jacobs, Eddy L.

    1981-01-01

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5 Mev neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  18. Arsenic activation neutron detector

    DOEpatents

    Jacobs, E.L.

    1980-01-28

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5-MeV neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

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

    SciTech Connect

    Gong, Gordon; Basom, Janet; Mattevada, Sravan; Onger, Frederick

    2015-04-15

    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 ≥8 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.

  20. [Effect of arsenic trioxide and 5-aza-2'-deoxycytidine on SHP-1, JAK3, TYK2 gene expression in K562 cells].

    PubMed

    Zhang, Xiao-Kun; Luo, Jian-Min; Sun, Jie

    2014-04-01

    This study was purposed to explore the effects of a methylation inhibitor arsenic trioxide (As2O3, ATO) and 5-Aza-2'-deoxycytidine (5-aza-CdR) on the expression of JAK-STAT signal transduction pathway in family members JAK3, TYK2 and hematopoietic cell phosphatase SHP-1 in chronic myeloid leukemia cell line K562 and their roles in pathogenesis of leukemia. The K562 cells were divided into 3 groups:single drug-treated group, combined 2 drugs-treated group, group without drug treatment as control. The concentration of 5-aza-CdR were 0.5, 1, 2 µmol/L; the concentration of ATO was 1, 2.5, 5 µmol/L; the concentration of combined drugs was ATO 1 µmol/L + 5-aza-CdR 0.5 µmol/L, ATO 2.5 µmol/L + 5-aza-CdR 1 µmol/L, and ATO 5 µmol/L + 5-aza-CdR 2 µmol/L. The K562 cells were treated with above-mentioned concentration of drugs for 24, 48 and 72 hours, then the total RNA of cells was extracted, the JAK3, TYK2 and SHP-1 expressions were detected by real-time quantitative-PCR. The results showed that after the K562 cells were treated with ATO and 5-aza-CdR alone and their combination, the expression of SHP-1 mRNA increased, the expressions of JAK3 mRNA and TYK2 mRNA decreased along with increasing of concentration and prolonging of time, displaying the concentration and time-dependency. The SHP-1 negatively related with JAK3 and TYK2. The effect of SHP-1 on JAK3 was significantly higher than that on TYK2. It is concluded that when the K562 cells are treated with ATO and 5-aza-CdR alone and their combination, the expression of SHP-1 is up-regulated and the expressions of JAK3, TYK2 are down-regulated in concentration-and time-dependent manners, moreover the ATO and 5-aza-CdR show synergies demethylation effect. The SHP-1 gene exert effect possibly through inhibiting the JAK/STAT pathway, the JAK3 is affected more than TYK2, the JAK3 may exert more important role in TAK/STAT pathway.

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

    SciTech Connect

    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.; and others

    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. - 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

  2. Biotransformation of arsenic by a Yellowstone thermoacidophilic eukaryotic alga

    PubMed Central

    Qin, Jie; Lehr, Corinne R.; Yuan, Chungang; Le, X. Chris; McDermott, Timothy R.; Rosen, Barry P.

    2009-01-01

    Arsenic is the most common toxic substance in the environment, ranking first on the Superfund list of hazardous substances. It is introduced primarily from geochemical sources and is acted on biologically, creating an arsenic biogeocycle. Geothermal environments are known for their elevated arsenic content and thus provide an excellent setting in which to study microbial redox transformations of arsenic. To date, most studies of microbial communities in geothermal environments have focused on Bacteria and Archaea, with little attention to eukaryotic microorganisms. Here, we show the potential of an extremophilic eukaryotic alga of the order Cyanidiales to influence arsenic cycling at elevated temperatures. Cyanidioschyzon sp. isolate 5508 oxidized arsenite [As(III)] to arsenate [As(V)], reduced As(V) to As(III), and methylated As(III) to form trimethylarsine oxide (TMAO) and dimethylarsenate [DMAs(V)]. Two arsenic methyltransferase genes, CmarsM7 and CmarsM8, were cloned from this organism and demonstrated to confer resistance to As(III) in an arsenite hypersensitive strain of Escherichia coli. The 2 recombinant CmArsMs were purified and shown to transform As(III) into monomethylarsenite, DMAs(V), TMAO, and trimethylarsine gas, with a Topt of 60–70 °C. These studies illustrate the importance of eukaryotic microorganisms to the biogeochemical cycling of arsenic in geothermal systems, offer a molecular explanation for how these algae tolerate arsenic in their environment, and provide the characterization of algal methyltransferases. PMID:19276121

  3. 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

  4. Arsenic Disruption of DNA Damage Responses—Potential Role in Carcinogenesis and Chemotherapy

    PubMed Central

    Muenyi, Clarisse S.; Ljungman, Mats; States, J. Christopher

    2015-01-01

    Arsenic is a Class I human carcinogen and is widespread in the environment. Chronic arsenic exposure causes cancer in skin, lung and bladder, as well as in other organs. Paradoxically, arsenic also is a potent chemotherapeutic against acute promyelocytic leukemia and can potentiate the cytotoxic effects of DNA damaging chemotherapeutics, such as cisplatin, in vitro. Arsenic has long been implicated in DNA repair inhibition, cell cycle disruption, and ubiquitination dysregulation, all negatively impacting the DNA damage response and potentially contributing to both the carcinogenic and chemotherapeutic potential of arsenic. Recent studies have provided mechanistic insights into how arsenic interferes with these processes including disruption of zinc fingers and suppression of gene expression. This review discusses these effects of arsenic with a view toward understanding the impact on the DNA damage response. PMID:26404387

  5. Polymorphisms in DNA repair genes XRCC1 and XRCC3, occupational exposure to arsenic and sunlight, and the risk of non-melanoma skin cancer in a European case-control study.

    PubMed

    Surdu, Simona; Fitzgerald, Edward F; Bloom, Michael S; Boscoe, Francis P; Carpenter, David O; Haase, Richard F; Gurzau, Eugen; Rudnai, Peter; Koppova, Kvetoslava; Vahter, Marie; Leonardi, Giovanni; Goessler, Walter; Kumar, Rajiv; Fletcher, Tony

    2014-10-01

    X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3) polymorphisms are relatively frequent in Caucasian populations and may have implications in skin cancer modulation. A few studies have evaluated their association with non-melanoma skin cancer (NMSC), but the results are inconsistent. In the current study, we aim to assess the impact of XRCC1 R399Q and XRCC3 T241M polymorphisms on the risk of NMSC associated with sunlight and arsenic exposure. Study participants consist of 618 new cases of NMSC and 527 hospital-based controls frequency matched on age, sex, and county of residence from Hungary, Romania, and Slovakia. Adjusted effects are estimated using multivariable logistic regression. The results indicate an increased risk of squamous cell carcinoma (SCC) for the homozygous variant genotype of XRCC1 R399Q (OR 2.53, 95% CI 1.14-5.65) and a protective effect against basal cell carcinoma (BCC) for the homozygous variant genotype of XRCC3 T241M (OR 0.61, 95% CI 0.41-0.92), compared with the respective homozygous common genotypes. Significant interactions are detected between XRCC3 T241M and sunlight exposure at work, and between XRCC3 T241M and exposure to arsenic in drinking water (p-value for interaction <0.10). In conclusion, the current study demonstrates that polymorphisms in XRCC genes may modify the associations between skin cancer risk and exposure to sunlight or arsenic. Given the high prevalence of genetic polymorphisms modifying the association between exposure to environmental carcinogens and NMSC, these results are of substantial relevance to public health.

  6. Kidneys and Urinary Tract

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Kidneys and Urinary Tract KidsHealth > For Teens > Kidneys and ... be a sign of diabetes . continue What the Kidneys and Urinary Tract Do Although the two kidneys ...

  7. Arsenic (+ 3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis.

    PubMed

    Thomas, David J; Nava, Gerardo M; Cai, Shi-Ying; Boyer, James L; Hernández-Zavala, Araceli; Gaskins, H Rex

    2010-01-01

    Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+ 3 oxidation state) methyltransferase (As3mt) yielding mono-, di-, and trimethylated arsenicals. To investigate the evolution of molecular mechanisms that mediate arsenic biotransformation, a comparative genomic approach focusing on the invertebrate chordate Ciona intestinalis was used. Bioinformatic analyses identified an As3mt gene in the C. intestinalis genome. Constitutive As3mt RNA expression was observed in heart, branchial sac, and gastrointestinal tract. Adult animals were exposed to 0 or 1 ppm of iAs for 1 or 5 days. Steady-state As3mt RNA expression in the gastrointestinal tract was not modulated significantly by 5 days of exposure to iAs. Tissue levels of iAs and its methylated metabolites were determined by hydride generation-cryotrapping-gas chromatography-atomic absorption spectrometry. At either time point, exposure to iAs significantly increased concentrations of iAs and its methylated metabolites in tissues. After 5 days of exposure, total speciated arsenic concentrations were highest in branchial sac (3705 ng/g), followed by heart (1019 ng/g) and gastrointestinal tract (835 ng/g). At this time point, the sum of the speciated arsenical concentrations in gastrointestinal tract and heart equaled or exceeded that of iAs; in branchial sac, iAs was the predominant species present. Ciona intestinalis metabolizes iAs to its methylated metabolites, which are retained in tissues. This metabolic pattern is consistent with the presence of an As3mt ortholog in its genome and constitutive expression of the gene in prominent organs, making this basal chordate a useful model to examine the evolution of arsenic detoxification.

  8. Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

    SciTech Connect

    Beatson, Scott A.; Ben Zakour, Nouri L.; Totsika, Makrina; Forde, Brian M.; Watts, Rebecca E.; Mabbett, Amanda N.; Szubert, Jan M.; Sarkar, Sohinee; Phan, Minh-Duy; Peters, Kate M.; Petty, Nicola K.; Alikhan, Nabil-Fareed; Sullivan, Mitchell J.; Gawthorne, Jayde A.; Stanton-Cook, Mitchell; Nhu, Nguyen Thi Khanh; Chong, Teik Min; Yin, Wai-Fong; Chan, Kok-Gan; Hancock, Viktoria; Ussery, David W.; Ulett, Glen C.; Schembri, Mark A

    2015-05-01

    Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. Here, to understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. In conlusion, our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder.

  9. Differential urinary specific gravity as a molecular phenotype of the bladder cancer genetic association in the urea transporter gene, SLC14A1.

    PubMed

    Koutros, Stella; Baris, Dalsu; Fischer, Alexander; Tang, Wei; Garcia-Closas, Montserrat; Karagas, Margaret R; Schwenn, Molly; Johnson, Alison; Figueroa, Jonine; Waddell, Richard; Prokunina-Olsson, Ludmila; Rothman, Nathaniel; Silverman, Debra T

    2013-12-15

    Genome-wide association studies (GWAS) identified associations between markers within the solute carrier family 14 (urea transporter), member 1 (SLC14A1) gene and risk of bladder cancer. SLC14A1 defines the Kidd blood groups in erythrocytes and is also involved in concentration of the urine in the kidney. We evaluated the association between a representative genetic variant (rs10775480) of SLC14A1 and urine concentration, as measured by urinary specific gravity (USG), in a subset of 275 population-based controls enrolled in the New England Bladder Cancer Study. Overnight urine samples were collected, and USG was measured using refractometry. Analysis of covariance was used to estimate adjusted least square means for USG in relation to rs10775480. We also examined the mRNA expression of both urea transporters, SLC14A1 and SLC14A2, in a panel of human tissues. USG was decreased with each copy of the rs10775480 risk T allele (p-trend = 0.011) with a significant difference observed for CC vs. TT genotypes (p-value(tukey) = 0.024). RNA-sequencing in the bladder tissue showed high expression of SLC14A1 and the absence of SLC14A2, while both transporters were expressed in the kidney. We suggest that the molecular phenotype of this GWAS finding is the genotype-specific biological activity of SLC14A1 in the bladder tissue. Our data suggest that SLC14A1 could be a unique urea transporter in the bladder that has the ability to influence urine concentration and that this mechanism might explain the increased bladder cancer susceptibility associated with rs10775480.

  10. Purification of Arsenic (+3 Oxidation State) Methyltransferase from Rat Liver Cytosol

    PubMed Central

    Drobna, Zuzana; Styblo, Miroslav; Thomas, David J.

    2015-01-01

    Demonstrating the enzymatic basis of arsenic methylation is critical to further studies of the pathway for the conversion of inorganic arsenic into a variety of methylated metabolites. This protocol describes a procedure for the purification of an arsenic methyltransferase from rat liver cytosol. Purification of this enzyme and subsequent cloning of its gene has permitted studies of enzyme structure and function and has lead to the identification of orthologous genes in genomes of organisms ranging in complexity from sea urchins to humans. These proteins are referred to as arsenic (+3 oxidation state) methyltransferases. PMID:20949431

  11. Arsenic exposure to killifish during embryogenesis alters muscle development.

    PubMed

    Gaworecki, Kristen M; Chapman, Robert W; Neely, Marion G; D'Amico, Angela R; Bain, Lisa J

    2012-02-01

    Epidemiological studies have correlated arsenic exposure in drinking water with adverse developmental outcomes such as stillbirths, spontaneous abortions, neonatal mortality, low birth weight, delays in the use of musculature, and altered locomotor activity. Killifish (Fundulus heteroclitus) were used as a model to help to determine the mechanisms by which arsenic could impact development. Killifish embryos were exposed to three different sodium arsenite concentrations and were collected at 32 h post-fertilization (hpf), 42 hpf, 168 hpf, or < 24 h post-hatch. A killifish oligo microarray was developed and used to examine gene expression changes between control and 25-ppm arsenic-exposed hatchlings. With artificial neural network analysis of the transcriptomic data, accurate prediction of each group (control vs. arsenic-exposed embryos) was obtained using a small subset of only 332 genes. The genes differentially expressed include those involved in cell cycle, development, ubiquitination, and the musculature. Several of the genes involved in cell cycle regulation and muscle formation, such as fetuin B, cyclin D-binding protein 1, and CapZ, were differentially expressed in the embryos in a time- and dose-dependent manner. Examining muscle structure in the hatchlings showed that arsenic exposure during embryogenesis significantly reduces the average muscle fiber size, which is coupled with a significant 2.1- and 1.6-fold upregulation of skeletal myosin light and heavy chains, respectively. These findings collectively indicate that arsenic exposure during embryogenesis can initiate molecular changes that appear to lead to aberrant muscle formation.

  12. 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

  13. Water hyacinth removes arsenic from arsenic-contaminated drinking water.

    PubMed

    Misbahuddin, Mir; Fariduddin, Atm

    2002-01-01

    Water hyacinth (Eichhornia crassipes) removes arsenic from arsenic-contaminated drinking water. This effect depends on several factors, such as the amount of water hyacinth, amount of arsenic present in the water, duration of exposure, and presence of sunlight and air. On the basis of the present study, the authors suggest that water hyacinth is useful for making arsenic-contaminated drinking water totally arsenic free. Water hyacinth provides a natural means of removing arsenic from drinking water at the household level without monetary cost.

  14. Effect of arsenic on p53 mutation and occurrence of teratogenic salamanders: their potential as ecological indicators for arsenic contamination.

    PubMed

    Chang, Jin-Soo; Gu, Man Bock; Kim, Kyoung-Woong

    2009-05-01

    The p53 mutation in salamanders can be used as an indicator of arsenic contamination. The influence of arsenic exposure was studied on mutation of tumor suppressor gene in salamanders collected from several As-contaminated mine areas in Korea. Salamander eggs and larvae were exposed to arsenic in a toxicity test, and teratogenic salamanders found in heavy metal- and As-contaminated water from As-Bi mines were evaluated using PCR-SSCP to determine if they would be useful as an ecological indicator species. Changes in amino acids were shown to have occurred as a result of an arsenic-accumulating event that occurred after the DNA damage. In addition, both of the Hynobius leechii exposed groups were primarily affected by forms of skin damage, changes in the lateral tail/dorsal flexure and/or abnormality teratogenesis. Single-base sense mutation in codons 346 (AAG: Lys to ATG: Met), 224 (TTT: Phe to TTA: Leu), 211 (ATG: Met to AAG: Lys), 244 (TTT: Phe to TTTG: insertion), 245 (Glu GAG to Gln CAG) and 249 (TGT Cys to TGA stop) of the p53 gene were simultaneously found in mutated salamanders. Based on the results of our data illustrating the effect of arsenic exposure on the p53 mutation of salamanders in arsenic-contaminated mine areas, these mutated salamanders can be used as potential ecological indicators in the arsenic-contaminated ecosystems.

  15. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence.

    PubMed

    Pearce, Meghan M; Hilt, Evann E; Rosenfeld, Amy B; Zilliox, Michael J; Thomas-White, Krystal; Fok, Cynthia; Kliethermes, Stephanie; Schreckenberger, Paul C; Brubaker, Linda; Gai, Xiaowu; Wolfe, Alan J

    2014-07-08

    Bacterial DNA and live bacteria have been detected in human urine in the absence of clinical infection, challenging the prevailing dogma that urine is normally sterile. Urgency urinary incontinence (UUI) is a poorly understood urinary condition characterized by symptoms that overlap urinary infection, including urinary urgency and increased frequency with urinary incontinence. The recent discovery of the urinary microbiome warrants investigation into whether bacteria contribute to UUI. In this study, we used 16S rRNA gene sequencing to classify bacterial DNA and expanded quantitative urine culture (EQUC) techniques to isolate live bacteria in urine collected by using a transurethral catheter from women with UUI and, in comparison, a cohort without UUI. For these cohorts, we demonstrated that the UUI and non-UUI urinary microbiomes differ by group based on both sequence and culture evidences. Compared to the non-UUI microbiome, sequencing experiments revealed that the UUI microbiome was composed of increased Gardnerella and decreased Lactobacillus. Nine genera (Actinobaculum, Actinomyces, Aerococcus, Arthrobacter, Corynebacterium, Gardnerella, Oligella, Staphylococcus, and Streptococcus) were more frequently cultured from the UUI cohort. Although Lactobacillus was isolated from both cohorts, distinctions existed at the species level, with Lactobacillus gasseri detected more frequently in the UUI cohort and Lactobacillus crispatus most frequently detected in controls. Combined, these data suggest that potentially important differences exist in the urinary microbiomes of women with and without UUI, which have strong implications in prevention, diagnosis, or treatment of UUI. Importance: New evidence indicates that the human urinary tract contains microbial communities; however, the role of these communities in urinary health remains to be elucidated. Urgency urinary incontinence (UUI) is a highly prevalent yet poorly understood urinary condition characterized by

  16. Role of Aspergillus niger acrA in Arsenic Resistance and Its Use as the Basis for an Arsenic Biosensor

    PubMed Central

    Choe, Se-In; Gravelat, Fabrice N.; Al Abdallah, Qusai; Lee, Mark J.; Gibbs, Bernard F.

    2012-01-01

    Arsenic contamination of groundwater sources is a major issue worldwide, since exposure to high levels of arsenic has been linked to a variety of health problems. Effective methods of detection are thus greatly needed as preventive measures. In an effort to develop a fungal biosensor for arsenic, we first identified seven putative arsenic metabolism and transport genes in Aspergillus niger, a widely used industrial organism that is generally regarded as safe (GRAS). Among the genes tested for RNA expression in response to arsenate, acrA, encoding a putative plasma membrane arsenite efflux pump, displayed an over 200-fold increase in gene expression in response to arsenate. We characterized the function of this A. niger protein in arsenic efflux by gene knockout and confirmed that AcrA was located at the cell membrane using an enhanced green fluorescent protein (eGFP) fusion construct. Based on our observations, we developed a putative biosensor strain containing a construct of the native promoter of acrA fused with egfp. We analyzed the fluorescence of this biosensor strain in the presence of arsenic using confocal microscopy and spectrofluorimetry. The biosensor strain reliably detected both arsenite and arsenate in the range of 1.8 to 180 μg/liter, which encompasses the threshold concentrations for drinking water set by the World Health Organization (10 and 50 μg/liter). PMID:22467499

  17. Role of Aspergillus niger acrA in arsenic resistance and its use as the basis for an arsenic biosensor.

    PubMed

    Choe, Se-In; Gravelat, Fabrice N; Al Abdallah, Qusai; Lee, Mark J; Gibbs, Bernard F; Sheppard, Donald C

    2012-06-01

    Arsenic contamination of groundwater sources is a major issue worldwide, since exposure to high levels of arsenic has been linked to a variety of health problems. Effective methods of detection are thus greatly needed as preventive measures. In an effort to develop a fungal biosensor for arsenic, we first identified seven putative arsenic metabolism and transport genes in Aspergillus niger, a widely used industrial organism that is generally regarded as safe (GRAS). Among the genes tested for RNA expression in response to arsenate, acrA, encoding a putative plasma membrane arsenite efflux pump, displayed an over 200-fold increase in gene expression in response to arsenate. We characterized the function of this A. niger protein in arsenic efflux by gene knockout and confirmed that AcrA was located at the cell membrane using an enhanced green fluorescent protein (eGFP) fusion construct. Based on our observations, we developed a putative biosensor strain containing a construct of the native promoter of acrA fused with egfp. We analyzed the fluorescence of this biosensor strain in the presence of arsenic using confocal microscopy and spectrofluorimetry. The biosensor strain reliably detected both arsenite and arsenate in the range of 1.8 to 180 μg/liter, which encompasses the threshold concentrations for drinking water set by the World Health Organization (10 and 50 μg/liter).

  18. Arsenic removal from contaminated soil via biovolatilization by genetically engineered bacteria under laboratory conditions.

    PubMed

    Liu, Shuang; Zhang, Fan; Chen, Jian; Sun, Guoxin

    2011-01-01

    In Rhodopseudomonas palustris, an arsM gene, encoding bacterial and archaeal homologues of the mammalian Cyt19 As(III) S-adenosylmethionine methytransferase, was regulated by arsenicals. An expression of arsM was introduced into strains for the methylation of arsenic. When arsM was expressed in Sphingomonas desiccabilis and Bacillus idriensis, it had 10 folds increase of methyled arsenic gas compared to wild type in aqueous system. In soil system, about 2.2%-4.5% of arsenic was removed by biovolatilization during 30 days. This study demonstrated that arsenic could be removed through volatilization from the contaminated soil by bacteria which have arsM gene expressed. These results showed that it is possible to use microorganisms expressing arsM as an inexpensive, efficient strategy for arsenic bioremediation from contaminated water and soil.

  19. Genetic and Molecular Dissection of Arsenic Hyperaccumulation

    SciTech Connect

    Banks, Jo Ann

    2005-06-01

    We have constructed cDNA libraries from RNA isolated from arsenic treated gametophytes of the fern Pteris vittata. This library was made in a manner that allows each cDNA clone to be expressed in yeast. We have introduced this library into yeast cells, both wild type and arsensic sensitive mutants, and selected transformed yeast colonies with increased arsenic tolerance compared to the parental strains. From these screens we have identified putative homologs of the yeast ACR2 and ACR3 genes from Pteris vittata and, for the past year, have focused on characterizing the function of the ACR2 gene. In yeast, ACR2 is an arsenate reductase that is essential for arsenate tolerance. We refer to the Pteris vittata ACR2 gene as PvACR2. The deduced amino acid sequence of PvACR2 is highly similar to the yeast ACR2 and other related phosphatases.

  20. Chromated Arsenicals (CCA)

    EPA Pesticide Factsheets

    Chromated copper arsenate (CCA) is a wood preservative pesticide containing chromium, copper, and arsenic that protects wood against termites, fungi, mites and other pests that can degrade or threaten the integrity of wood products.

  1. ENZYMOLOGY OF ARSENIC METHYLATION

    EPA Science Inventory

    Enzymology of Arsenic Methylation

    David J. Thomas, Pharmacokinetics Branch, Experimental Toxicology Division, National
    Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park...

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

    SciTech Connect

    Ren, Xuefeng; Gaile, Daniel P.; Gong, Zhihong; Qiu, Wenting; Ge, Yichen; Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao; Olson, James R.; Kavanagh, Terrance J.; Wu, Hongmei

    2015-03-15

    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 arsenic 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

  3. Methylation of Arsenic by Recombinant Human Wild-Type Arsenic (+3 Oxidation State) Methyltransferase and its Methionine 287 Threonine (M287T) Polymorph

    EPA Science Inventory

    ABSTRACT Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the pathway for methylation of arsenicals. A common polymorphism in the AS3MT gene that replaces a threonyl residue in position 287 with a methionyl residue (AS3MT/M287T) occurs at a frequency...

  4. 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...

  5. Carbon and arsenic metabolism in Thiomonas strains: differences revealed diverse adaptation processes

    PubMed Central

    2009-01-01

    Background Thiomonas strains are ubiquitous in arsenic-contaminated environments. Differences between Thiomonas strains in the way they have adapted and respond to arsenic have never been studied in detail. For this purpose, five Thiomonas strains, that are interesting in terms of arsenic metabolism were selected: T. arsenivorans, Thiomonas spp. WJ68 and 3As are able to oxidise As(III), while Thiomonas sp. Ynys1 and T. perometabolis are not. Moreover, T. arsenivorans and 3As present interesting physiological traits, in particular that these strains are able to use As(III) as an electron donor. Results The metabolism of carbon and arsenic was compared in the five Thiomonas strains belonging to two distinct phylogenetic groups. Greater physiological differences were found between these strains than might have been suggested by 16S rRNA/rpoA gene phylogeny, especially regarding arsenic metabolism. Physiologically, T. perometabolis and Ynys1 were unable to oxidise As(III) and were less arsenic-resistant than the other strains. Genetically, they appeared to lack the aox arsenic-oxidising genes and carried only a single ars arsenic resistance operon. Thiomonas arsenivorans belonged to a distinct phylogenetic group and increased its autotrophic metabolism when arsenic concentration increased. Differential proteomic analysis revealed that in T. arsenivorans, the rbc/cbb genes involved in the assimilation of inorganic carbon were induced in the presence of arsenic, whereas these genes were repressed in Thiomonas sp. 3As. Conclusion Taken together, these results show that these closely related bacteria differ substantially in their response to arsenic, amongst other factors, and suggest different relationships between carbon assimilation and arsenic metabolism. PMID:19549320

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

    SciTech Connect

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

    2014-01-15

    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 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. - 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.

  7. 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;

  8. Genetic association between intronic variants in AS3MT and arsenic methylation efficiency is focused on a large linkage disequilibrium cluster in chromosome 10.

    PubMed

    Gomez-Rubio, Paulina; Meza-Montenegro, Maria M; Cantu-Soto, Ernesto; Klimecki, Walter T

    2010-04-01

    Differences in arsenic metabolism are known to play a role in individual variability in arsenic-induced disease susceptibility. Genetic variants in genes relevant to arsenic metabolism are considered to be partially responsible for the variation in arsenic metabolism. Specifically, variants in arsenic (3+ oxidation state) methyltransferase (AS3MT), the key gene in the metabolism of arsenic, have been associated with increased arsenic methylation efficiency. Of particular interest is the fact that different studies have reported that several of the AS3MT single nucleotide polymorphisms (SNPs) are in strong linkage-disequilibrium (LD), which also extends to a nearby gene, CYP17A1. In an effort to characterize the extent of the region in LD, we genotyped 46 SNPs in a 347,000 base region of chromosome 10 that included AS3MT in arsenic-exposed subjects from Mexico. Pairwise LD analysis showed strong LD for these polymorphisms, represented by a mean r(2) of 0.82, spanning a region that includes five genes. Genetic association analysis with arsenic metabolism confirmed the previously observed association between AS3MT variants, including this large cluster of linked polymorphisms, and arsenic methylation efficiency. The existence of a large genomic region sharing strong LD with polymorphisms associated with arsenic metabolism presents a predicament because the observed phenotype cannot be unequivocally assigned to a single SNP or even a single gene. The results reported here should be carefully considered for future genomic association studies involving AS3MT and arsenic metabolism.

  9. Assessment of exposure to soils contaminated with lead, cadmium, and arsenic near a zinc smelter, Cassiopée Study, France, 2008.

    PubMed

    Durand, Cécile; Sauthier, Nicolas; Schwoebel, Valérie

    2015-06-01

    After 150 years of industrial activity, significant pollution of surface soils in private gardens and locally produced vegetables with lead, cadmium, and arsenic has recently been observed in Viviez (Southern France). A public health intervention was conducted in 2008 to identify individual health risks of Viviez inhabitants and to analyze their environmental exposure to these pollutants. Children and pregnant women in Viviez were screened for lead poisoning. Urinary cadmium testing was proposed to all inhabitants. Those with urinary cadmium levels over 1 μg/g creatinine were then tested for kidney damage. Urinary cadmium and arsenic levels were compared between participants with non-occupational exposure from Viviez and Montbazens, a nearby town not exposed to these two pollutants, in order to identify environmental factors contributing to impregnation. No case of lead poisoning was detected in Viviez, but 23 % of adults had urinary cadmium over 1 μg/g creatinine, 14 % of whom having markers of kidney damage. Viviez adults had higher levels of urinary cadmium, and to a lesser extent, higher levels of urinary arsenic than those from Montbazens. Consumption of local produce (vegetables and animals) and length of residence in Viviez were associated with higher urinary cadmium levels, independently of known confounding factors, suggesting persisting environmental exposure to contaminated soil. To conclude, health risks related to cadmium exposure were identified in the Viviez population living on contaminated soils. Lead and arsenic exposure did not pose health concerns. Interventions were proposed to reduce exposure and limit health consequences.

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

    PubMed Central

    Ren, Xuefeng; Gaile, Daniel P.; Gong, Zhihong; Qiu, Wenting; Ge, Yichen; Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao; Olson, James R.; Kavanagh, Terrance J.; Wu, Hongmei

    2015-01-01

    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 arsenic 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. PMID:25625412

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

    PubMed

    Ren, Xuefeng; Gaile, Daniel P; Gong, Zhihong; Qiu, Wenting; Ge, Yichen; Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao; Olson, James R; Kavanagh, Terrance J; Wu, Hongmei

    2015-03-15

    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 100mg/L) for 60days. 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 arsenic 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.

  12. Treating chronic arsenic toxicity with high selenium lentil diets

    SciTech Connect

    Sah, Shweta; Vandenberg, Albert; Smits, Judit

    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 compare 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

  13. A prospective study of the synergistic effects of arsenic exposure and smoking, sun exposure, fertilizer use, and pesticide use on risk of premalignant skin lesions in Bangladeshi men.

    PubMed

    Melkonian, Stephanie; Argos, Maria; Pierce, Brandon L; Chen, Yu; Islam, Tariqul; Ahmed, Alauddin; Syed, Emdadul H; Parvez, Faruque; Graziano, Joseph; Rathouz, Paul J; Ahsan, Habibul

    2011-01-15

    Skin lesions are classic clinical signs of toxicity due to long-term exposure to arsenic, and they are considered precursors to arsenic-related skin cancer. The authors prospectively evaluated synergisms between effects of arsenic exposure and those of tobacco use, sun exposure, and pesticide and fertilizer use on incident skin lesions using risk factor data from 5,042 men from the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, which recruited participants from October 2000 to May 2002. Discrete time hazard models were used to estimate measures of synergistic interactions on the additive scale. The authors observed significant synergistic effects between various measures of arsenic exposure and smoking and fertilizer use. The relative excess risks for the interactions between smoking status and arsenic exposure were 0.12 (95% confidence interval: 0.06, 0.19) for water arsenic and 0.11 (95% confidence interval: 0.05, 0.15) for urinary arsenic measures, respectively. Significant synergistic effects were also observed between fertilizer use and water arsenic (relative excess risk for the interaction = 0.06, 95% confidence interval: 0.01, 0.12). This is the first prospective study based on individual-level data that supports a role for smoking and certain occupational risk factors in modification of the effect of long-term arsenic exposure on skin lesions. Understanding differential arsenic susceptibility allows researchers to develop interventions to prevent the health consequences of this massive problem in the Bangladeshi population and beyond.

  14. A Prospective Study of the Synergistic Effects of Arsenic Exposure and Smoking, Sun Exposure, Fertilizer Use, and Pesticide Use on Risk of Premalignant Skin Lesions in Bangladeshi Men

    PubMed Central

    Melkonian, Stephanie; Argos, Maria; Pierce, Brandon L.; Chen, Yu; Islam, Tariqul; Ahmed, Alauddin; Syed, Emdadul H.; Parvez, Faruque; Graziano, Joseph; Rathouz, Paul J.; Ahsan, Habibul

    2011-01-01

    Skin lesions are classic clinical signs of toxicity due to long-term exposure to arsenic, and they are considered precursors to arsenic-related skin cancer. The authors prospectively evaluated synergisms between effects of arsenic exposure and those of tobacco use, sun exposure, and pesticide and fertilizer use on incident skin lesions using risk factor data from 5,042 men from the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, which recruited participants from October 2000 to May 2002. Discrete time hazard models were used to estimate measures of synergistic interactions on the additive scale. The authors observed significant synergistic effects between various measures of arsenic exposure and smoking and fertilizer use. The relative excess risks for the interactions between smoking status and arsenic exposure were 0.12 (95% confidence interval: 0.06, 0.19) for water arsenic and 0.11 (95% confidence interval: 0.05, 0.15) for urinary arsenic measures, respectively. Significant synergistic effects were also observed between fertilizer use and water arsenic (relative excess risk for the interaction = 0.06, 95% confidence interval: 0.01, 0.12). This is the first prospective study based on individual-level data that supports a role for smoking and certain occupational risk factors in modification of the effect of long-term arsenic exposure on skin lesions. Understanding differential arsenic susceptibility allows researchers to develop interventions to prevent the health consequences of this massive problem in the Bangladeshi population and beyond. PMID:21098630

  15. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    SciTech Connect

    Srivastava, Pranay; Yadav, Rajesh S.; Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S.; Dwivedi, Hari N.; Pant, Aditiya B.; Khanna, Vinay K.

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  16. Microbial Community of High Arsenic Groundwater in Agricultural Irrigation Area of Hetao Plain, Inner Mongolia.

    PubMed

    Wang, Yanhong; Li, Ping; Jiang, Zhou; Sinkkonen, Aki; Wang, Shi; Tu, Jin; Wei, Dazhun; Dong, Hailiang; Wang, Yanxin

    2016-01-01

    Microbial communities can play important role in arsenic release in groundwater aquifers. To investigate the microbial communities in high arsenic groundwater aquifers in agricultural irrigation area, 17 groundwater samples with different arsenic concentrations were collected along the agricultural drainage channels of Hangjinhouqi County, Inner Mongolia and examined by illumina MiSeq sequencing approach targeting the V4 region of the 16S rRNA genes. Both principal component analysis and hierarchical clustering results indicated that these samples were divided into two groups (high and low arsenic groups) according to the variation of geochemical characteristics. Arsenic concentrations showed strongly positive correlations with [Formula: see text] and total organic carbon (TOC). Sequencing results revealed that a total of 329-2823 operational taxonomic units (OTUs) were observed at the 97% OTU level. Microbial richness and diversity of high arsenic groundwater samples along the drainage channels were lower than those of low arsenic groundwater samples but higher than those of high arsenic groundwaters from strongly reducing areas. The microbial community structure in groundwater along the drainage channels was different from those in strongly reducing arsenic-rich aquifers of Hetao Plain and other high arsenic groundwater aquifers including Bangladesh, West Bengal, and Vietnam. Acinetobacter and Pseudomonas dominated with high percentages in both high and low arsenic groundwaters. Alishewanella, Psychrobacter, Methylotenera, and Crenothrix showed relatively high abundances in high arsenic groundwater, while Rheinheimera and the unidentified OP3 were predominant populations in low arsenic groundwater. Archaeal populations displayed a low occurrence and mainly dominated by methanogens such as Methanocorpusculum and Methanospirillum. Microbial community compositions were different between high and low arsenic groundwater samples based on the results of principal

  17. Microbial Community of High Arsenic Groundwater in Agricultural Irrigation Area of Hetao Plain, Inner Mongolia

    PubMed Central

    Wang, Yanhong; Li, Ping; Jiang, Zhou; Sinkkonen, Aki; Wang, Shi; Tu, Jin; Wei, Dazhun; Dong, Hailiang; Wang, Yanxin

    2016-01-01

    Microbial communities can play important role in arsenic release in groundwater aquifers. To investigate the microbial communities in high arsenic groundwater aquifers in agricultural irrigation area, 17 groundwater samples with different arsenic concentrations were collected along the agricultural drainage channels of Hangjinhouqi County, Inner Mongolia and examined by illumina MiSeq sequencing approach targeting the V4 region of the 16S rRNA genes. Both principal component analysis and hierarchical clustering results indicated that these samples were divided into two groups (high and low arsenic groups) according to the variation of geochemical characteristics. Arsenic concentrations showed strongly positive correlations with NH4+ and total organic carbon (TOC). Sequencing results revealed that a total of 329–2823 operational taxonomic units (OTUs) were observed at the 97% OTU level. Microbial richness and diversity of high arsenic groundwater samples along the drainage channels were lower than those of low arsenic groundwater samples but higher than those of high arsenic groundwaters from strongly reducing areas. The microbial community structure in groundwater along the drainage channels was different from those in strongly reducing arsenic-rich aquifers of Hetao Plain and other high arsenic groundwater aquifers including Bangladesh, West Bengal, and Vietnam. Acinetobacter and Pseudomonas dominated with high percentages in both high and low arsenic groundwaters. Alishewanella, Psychrobacter, Methylotenera, and Crenothrix showed relatively high abundances in high arsenic groundwater, while Rheinheimera and the unidentified OP3 were predominant populations in low arsenic groundwater. Archaeal populations displayed a low occurrence and mainly dominated by methanogens such as Methanocorpusculum and Methanospirillum. Microbial community compositions were different between high and low arsenic groundwater samples based on the results of principal coordinate

  18. 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...

  19. Arsenic (Environmental Health Student Portal)

    MedlinePlus

    ... Pollutants Natural Disasters Drinking Water Waterborne Diseases & Illnesses Water Cycle Water Treatment Videos Games Experiments For Teachers Home ... Pollutants Natural Disasters Drinking Water Waterborne Diseases & Illnesses Water Cycle Water Treatment Arsenic The Basics Arsenic is an ...

  20. The Female Urinary Microbiome: a Comparison of Women with and without Urgency Urinary Incontinence

    PubMed Central

    Pearce, Meghan M.; Hilt, Evann E.; Rosenfeld, Amy B.; Zilliox, Michael J.; Thomas-White, Krystal; Fok, Cynthia; Kliethermes, Stephanie; Schreckenberger, Paul C.; Brubaker, Linda

    2014-01-01

    ABSTRACT Bacterial DNA and live bacteria have been detected in human urine in the absence of clinical infection, challenging the prevailing dogma that urine is normally sterile. Urgency urinary incontinence (UUI) is a poorly understood urinary condition characterized by symptoms that overlap urinary infection, including urinary urgency and increased frequency with urinary incontinence. The recent discovery of the urinary microbiome warrants investigation into whether bacteria contribute to UUI. In this study, we used 16S rRNA gene sequencing to classify bacterial DNA and expanded quantitative urine culture (EQUC) techniques to isolate live bacteria in urine collected by using a transurethral catheter from women with UUI and, in comparison, a cohort without UUI. For these cohorts, we demonstrated that the UUI and non-UUI urinary microbiomes differ by group based on both sequence and culture evidences. Compared to the non-UUI microbiome, sequencing experiments revealed that the UUI microbiome was composed of increased Gardnerella and decreased Lactobacillus. Nine genera (Actinobaculum, Actinomyces, Aerococcus, Arthrobacter, Corynebacterium, Gardnerella, Oligella, Staphylococcus, and Streptococcus) were more frequently cultured from the UUI cohort. Although Lactobacillus was isolated from both cohorts, distinctions existed at the species level, with Lactobacillus gasseri detected more frequently in the UUI cohort and Lactobacillus crispatus most frequently detected in controls. Combined, these data suggest that potentially important differences exist in the urinary microbiomes of women with and without UUI, which have strong implications in prevention, diagnosis, or treatment of UUI. PMID:25006228

  1. Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: Review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

    SciTech Connect

    Chen Yu; Parvez, Faruque; Gamble, Mary; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Graziano, Joseph H.; Ahsan, Habibul

    2009-09-01

    The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (> 300 {mu}g/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 {mu}g/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 {mu}g/L, mean 99 {mu}g/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention.

  2. ARSENIC REMOVAL COST ESTIMATING PROGRAM

    EPA Science Inventory

    The Arsenic Removal Cost Estimating program (Excel) calculates the costs for using adsorptive media and anion exchange treatment systems to remove arsenic from drinking water. The program is an easy-to-use tool to estimate capital and operating costs for three types of arsenic re...

  3. PATHWAY OF INORGANIC ARSENIC METABOLISM

    EPA Science Inventory

    A remarkable aspect of the metabolism of inorganic arsenic in humans is its conversion to methylated metabolites. These metabolites account for most of the arsenic found in urine after exposure to inorganic arsenic. At least some of the adverse health effects attributed to inor...

  4. The female urinary microbiota, urinary health and common urinary disorders

    PubMed Central

    Wolfe, Alan J.

    2017-01-01

    This review provides the clinical context and updated information regarding the female urinary microbiota (FUM), a resident microbial community within the female bladder of many adult women. Microbial communities have variability and distinct characteristics in health, as well as during community disruption (dysbiosis). Information concerning characteristics of the FUM in health and disease is emerging. Sufficient data confirms that the microbes that compose the FUM are not contaminants and are cultivatable under appropriate conditions. Common clinical conditions, including urinary tract infection (UTI) and urgency urinary incontinence (UUI), a common form of urinary incontinence (UI), may be usefully reconsidered to determine the role of the FUM. Knowledge of FUM characteristics may help advance prevention, diagnosis and treatment of these conditions and other common lower urinary disorders in women. The FUM appears related to UTI and UUI in adult women. The specific role of the FUM remains to be clarified and requires significant additional work in describing FUM variability and resilience in health. Unique aspects of the FUM prompt re-evaluation of existing nomenclature to more appropriately define health and disease; the concept of dysbiosis may be useful for understanding the interaction of the FUM with other aspects of lower urinary tract physiology, including urothelial signaling. Clinicians, through their clinical laboratories, can adopt enhanced urine culture techniques that more fully describe the living microbes within the FUM. This additional information may provide clinicians and their patients an opportunity to impact clinical care without antibiotic use, if the FUM can be appropriately modified to improve treatment precision for UTI and UUI. PMID:28217699

  5. Differential DNA Methylation in Umbilical Cord Blood of Infants Exposed to Low Levels of Arsenic in Utero

    PubMed Central

    Koestler, Devin C.; Avissar-Whiting, Michele; Houseman, E. Andres; Karagas, Margaret R.

    2013-01-01

    Background: There is increasing epidemiologic evidence that arsenic exposure in utero, even at low levels found throughout much of the world, is associated with adverse reproductive outcomes and may contribute to long-term health effects. Animal models, in vitro studies, and human cancer data suggest that arsenic may induce epigenetic alterations, specifically by altering patterns of DNA methylation. Objectives: In this study we aimed to identify differences in DNA methylation in cord blood samples of infants with in utero, low-level arsenic exposure. Methods: DNA methylation of cord-blood derived DNA from 134 infants involved in a prospective birth cohort in New Hampshire was profiled using the Illumina Infinium Methylation450K array. In utero arsenic exposure was estimated using maternal urine samples collected at 24–28 weeks gestation. We used a novel cell mixture deconvolution methodology for examining the association between inferred white blood cell mixtures in infant cord blood and in utero arsenic exposure; we also examined the association between methylation at individual CpG loci and arsenic exposure levels. Results: We found an association between urinary inorganic arsenic concentration and the estimated proportion of CD8+ T lymphocytes (1.18; 95% CI: 0.12, 2.23). Among the top 100 CpG loci with the lowest p-values based on their association with urinary arsenic levels, there was a statistically significant enrichment of these loci in CpG islands (p = 0.009). Of those in CpG islands (n = 44), most (75%) exhibited higher methylation levels in the highest exposed group compared with the lowest exposed group. Also, several CpG loci exhibited a linear dose-dependent relationship between methylation and arsenic exposure. Conclusions: Our findings suggest that in utero exposure to low levels of arsenic may affect the epigenome. Long-term follow-up is planned to determine whether the observed changes are associated with health outcomes. PMID:23757598

  6. Arsenic speciation in clinical samples: urine analysis using fast micro-liquid chromatography ICP-MS.

    PubMed

    Morton, Jackie; Leese, Elizabeth

    2011-02-01

    Arsenic speciation is a subject that is developing all the time both from improvements in analytical techniques and from increases in toxicological understanding. Despite speciation methods being widely developed, arsenic speciation is not routinely offered as an analysis in clinical laboratory. The work in this paper describes a simple routine method for arsenic speciation that could be easily implemented in clinical laboratories. The method described, a new, fast analytical method for arsenic speciation, is reported using micro-liquid chromatography hyphenated to an inductively coupled plasma mass spectrometer (μLC-ICP-MS). The method uses a low-pressure delivery six-port valve with a 5 cm anion exchange column, which allows a fully resolved separation of five arsenic species (arsenobetaine [AB], arsenite [As(3+)], arsenate [As(5+)], mono-methylarsonic acid [MMA(5+)] and dimethylarsinic acid [DMA(5+)]) in urine in just 6 min. This fast analytical method offers an arsenic speciation method that is feasible for a laboratory that does not have the capability for a dedicated arsenic speciation LC-ICP-MS instrument. The micro-LC system is small, easy to install and is fully integrated with the ICP-MS software. The results reported here are from urine samples from 65 workers in a semiconductor work providing a sample for their routine biological monitoring to assess workplace exposure. Control samples from 20 unexposed people were also determined. Results show that the semiconductor workers exhibit very low levels of arsenic in their urine samples, similar to the levels in the controls, and thus are not significantly exposed to arsenic. Care must be taken when interpreting urinary arsenic species results because it is not always possible to differentiate between dietary and other external sources of exposure.

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

    PubMed

    Gong, Gordon; Basom, Janet; Mattevada, Sravan; Onger, Frederick

    2015-04-01

    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 (2-22µg/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 ≥8µg/L in 36% of the subjects' wells while iodine concentration was <1µg/L in 91% of their wells. Logistic regression analysis showed that arsenic in groundwater ≥8µg/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 ≥8µg/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.

  8. Urinary incontinence in women.

    PubMed

    Norton, Peggy; Brubaker, Linda

    2006-01-07

    Urinary incontinence is common in women, but is under-reported and under-treated. Urine storage and emptying is a complex coordination between the bladder and urethra, and disturbances in the system due to childbirth, aging, or other medical conditions can lead to urinary incontinence. The two main types of incontinence in women, stress urinary incontinence and urge urinary incontinence, can be evaluated by history and simple clinical assessment available to most primary care physicians. There is a wide range of therapeutic options, but the recent proliferation of new drug treatments and surgical devices for urinary incontinence have had mixed results; direct-to-consumer advertising has increased public awareness of the problem of urinary incontinence, but many new products are being introduced without long-term assessment of their safety and efficacy.

  9. Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis

    EPA Science Inventory

    Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+3 oxidation state) methyltransferase (As3mt), yielding mono- , di- , and trimethylated arsenicals. To investigate the evolution of molecular mechanisms that mediate arsenic biotransformation,...

  10. An Emerging Role for Epigenetic Dysregulation in Arsenic Toxicity and Carcinogenesis

    PubMed Central

    Ren, Xuefeng; McHale, Cliona M.; Skibola, Christine F.; Smith, Allan H.; Smith, Martyn T.; Zhang, Luoping

    2011-01-01

    Background Exposure to arsenic, an established human carcinogen, through consumption of highly contaminated drinking water is a worldwide public health concern. Several mechanisms by which arsenical compounds induce tumorigenesis have been proposed, including oxidative stress, genotoxic damage, and chromosomal abnormalities. Recent studies have suggested that epigenetic mechanisms may also mediate toxicity and carcinogenicity resulting from arsenic exposure. Objective We examined the evidence supporting the roles of the three major epigenetic mechanisms—DNA methylation, histone modification, and microRNA (miRNA) expression—in arsenic toxicity and, in particular, carcinogenicity. We also investigated future research directions necessary to clarify epigenetic and other mechanisms in humans. Data sources and synthesis We conducted a PubMed search of arsenic exposure and epigenetic modification through April 2010 and summarized the in vitro and in vivo research findings, from both our group and others, on arsenic-associated epigenetic alteration and its potential role in toxicity and carcinogenicity. Conclusions Arsenic exposure has been shown to alter methylation levels of both global DNA and gene promoters; histone acetylation, methylation, and phosphorylation; and miRNA expression, in studies analyzing mainly a limited number of epigenetic end points. Systematic epigenomic studies in human populations exposed to arsenic or in patients with arsenic-associated cancer have not yet been performed. Such studies would help to elucidate the relationship between arsenic exposure, epigenetic dysregulation, and carcinogenesis and are becoming feasible because of recent technological advancements. PMID:20682481

  11. Identification of differentially expressed genes in the livers of chronically i-As-treated hamsters.

    PubMed

    Hernández, Alba; Sampayo-Reyes, Adriana; Marcos, Ricard

    2011-08-01

    Inorganic arsenic (i-As) is a human carcinogen causing skin, lung, urinary bladder, liver and kidney tumors. Chronic exposure to this naturally occurring contaminant, mainly via drinking water, is a significant worldwide environmental health concern. To explore the molecular mechanisms of arsenic hepatic injury, a differential display polymerase chain reaction (DD-PCR) screening was undertaken to identify genes with distinct expression patterns between the liver of low i-As-exposed and control animals. Golden Syrian hamsters (5-6 weeks of age) received drinking water containing 15 mg i-As/L as sodium arsenite, or unaltered water for 18 weeks. The in vivo MN test was carried out, and the frequency of micronucleated reticulocytes (MN-RETs) was scored as a measure of exposure and As-related genotoxic/carcinogenic risk. A total of 68 differentially expressed bands were identified in our initial screen, 41 of which could be assigned to specific genes. Differential level of expression of a selected number of genes was verified using real-time RT-PCR with gene-specific primers. Arsenic-altered gene expression included genes related to stress response, cellular metabolism, cell cycle regulation, telomere maintenance, cell-cell communication and signal transduction. Significant differences of MN-RET were found between treated (8.70 ± 0.02 MN/1000RETs) and control (2.5 ± 0.70 MN/1000RETs) groups (P<0.001), demonstrating both the exposure and the i-As genotoxic/carcinogenic risk. Overall, this paper reveals some possible networks involved in hepatic arsenic-related genotoxicity, carcinogenesis and diabetogenesis. Additional studies to explore further the potential implications of each candidate gene are of especial interest. The present work opens the door to new prospects for the study of i-As mechanisms taking place in the liver under chronic settings.

  12. [Arsenic - Poison or medicine?].

    PubMed

    Kulik-Kupka, Karolina; Koszowska, Aneta; Brończyk-Puzoń, Anna; Nowak, Justyna; Gwizdek, Katarzyna; Zubelewicz-Szkodzińska, Barbara

    2016-01-01

    Arsenic (As) is commonly known as a poison. Only a few people know that As has also been widely used in medicine. In the past years As and its compounds were used as a medicine for the treatment of such diseases as diabetes, psoriasis, syphilis, skin ulcers and joint diseases. Nowadays As is also used especially in the treatment of patients with acute promyelocytic leukemia. The International Agency for Research on Cancer (IARC) has recognized arsenic as an element with carcinogenic effect evidenced by epidemiological studies, but as previously mentioned it is also used in the treatment of neoplastic diseases. This underlines the specificity of the arsenic effects. Arsenic occurs widely in the natural environment, for example, it is present in soil and water, which contributes to its migration to food products. Long exposure to this element may lead to liver damages and also to changes in myocardium. Bearing in mind that such serious health problems can occur, monitoring of the As presence in the environmental media plays a very important role. In addition, the occupational risk of As exposure in the workplace should be identified and checked. Also the standards for As presence in food should be established. This paper presents a review of the 2015 publications based on the Medical database like PubMed and Polish Medical Bibliography. It includes the most important information about arsenic in both forms, poison and medicine.

  13. Arsenic: The Silent Killer

    SciTech Connect

    Foster, Andrea

    2006-02-28

    Andrea Foster uses x-rays to determine the forms of potentially toxic elements in environmentally-important matrices such as water, sediments, plants, and microorganisms. In this free public lecture, Foster will discuss her research on arsenic, which is called the silent killer because dissolved in water, it is colorless, odorless, and tasteless, yet consumption of relatively small doses of this element in its most toxic forms can cause rapid and violent death. Arsenic is a well-known poison, and has been used as such since ancient times. Less well known is the fact that much lower doses of the element, consumed over years, can lead to a variety of skin and internal cancers that can also be fatal. Currently, what has been called the largest mass poisoning in history is occurring in Bangladesh, where most people are by necessity drinking ground water that is contaminated with arsenic far in excess of the maximum amounts determined to be safe by the World Health Organization. This presentation will review the long and complicated history with arsenic, describe how x-rays have helped explain the high yet spatially variable arsenic concentrations in Bangladesh, discuss the ways in which land use in Bangladesh may be exacerbating the problem, and summarize the impact of this silent killer on drinking water systems worldwide.

  14. 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

    2017-02-11

    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 NaAsO2) 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.

  15. Assessment of lymphocyte subpopulations and cytokine secretion in children exposed to arsenic.

    PubMed

    Soto-Peña, Gerson A; Luna, Ana L; Acosta-Saavedra, Leonor; Conde, Patricia; López-Carrillo, Lizbeth; Cebrián, Mariano E; Bastida, Mariana; Calderón-Aranda, Emma S; Vega, Libia

    2006-04-01

    Exposure of several human populations to arsenic has been associated with a high incidence of detrimental dermatological and carcinogenic effects. To date, studies examining the immunotoxic effects of arsenic in humans, and specifically in children, are lacking. Therefore, we evaluated several parameters of immunological status in a group of children exposed to arsenic through their drinking water. Peripheral blood mononuclear cells (PBMCs) of 90 children (6 to 10 years old) were collected. Proportions of lymphocyte subpopulations, PBMC mitogenic proliferative response, and urinary arsenic levels were evaluated. Increased urine arsenic levels were associated with a reduced proliferative response to phytohemaglutinin (PHA) stimulation (P=0.005), CD4 subpopulation proportion (P=0.092), CD4/CD8 ratio (P=0.056), and IL-2 secretion levels (P=0.003). Increased arsenic exposure was also associated with an increase in GM-CSF secretion by mononucleated cells (P=0.000). We did not observe changes in CD8, B, or NK cell proportions, nor did we observe changes in the secretion of IL-4, IL-10, or IFN-gamma by PHA-activated PBMCs. These data indicate that arsenic exposure could alter the activation processes of T cells, such that an immunosuppression status that favors opportunistic infections and carcinogenesis is produced together with increased GM-CSF secretion that may be associated with chronic inflammation.

  16. Urinary catheter - infants

    MedlinePlus