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Sample records for arsenic trioxide anticancer

  1. 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 ...

  2. Inorganic phosphate-triggered release of anti-cancer arsenic trioxide from a self-delivery system: an in vitro and in vivo study

    NASA Astrophysics Data System (ADS)

    Chen, Fei-Yan; Yi, Jing-Wei; Gu, Zhe-Jia; Tang, Bin-Bing; Li, Jian-Qi; Li, Li; Kulkarni, Padmakar; Liu, Li; Mason, Ralph P.; Tang, Qun

    2016-03-01

    On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced toxicity compared to the free drug. These results suggest a new drug delivery strategy which might be applied for ATO therapy on solid tumors.On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced

  3. Arsenic Trioxide-Induced Mandibular Osteomyelitis.

    PubMed

    Lu, Pei-Chen; Wu, Ju-Hui; Chen, Chun-Ming; Du, Je-Kang

    2015-09-01

    Previously, arsenic was a popular devitalizing agent used to necrotize inflamed dental pulp to lower the pulp sensitivity owing to the unavailability of appropriate anesthesia. However, leakage from the apical foramen, lateral or accessory canals, or cracks in the tooth is common. This can be dangerous because of the reportedly high toxic effects of arsenic in both hard and soft tissues, leading to gingival and osseous necrosis and, consequently, osteomyelitis. Therefore, arsenic can prove fatal for both bones and teeth and is no longer used. We encountered a case involving a 50-year-old man who had developed mandibular osteomyelitis with lower lip paresthesia caused by arsenic trioxide used during endodontic treatment. The patient was treated with appropriate antibiotics, adjunctive hyperbaric oxygen therapy, and adequate surgical debridement. Hyperbaric oxygen therapy can induce neovascularization in necrosed tissues and improve bone and soft tissue healing. At a 4-year follow-up visit, bone healing was observed, with restoration of periodontal health, although the paresthesia had persisted. We describe this case, present a review of the relevant published data, and discuss the possible causes, diagnosis, treatment, and follow-up protocol of mandibular osteomyelitis caused by arsenic trioxide. PMID:25896568

  4. Arsenic Trioxide Negatively Affects Echinococcus granulosus

    PubMed Central

    Wang, Bo; Wang, Zhuo; Li, Fangfang; Xing, Guoqiang; Peng, Xinyu; Zhang, Shijie

    2015-01-01

    Spillage of cyst contents during surgery is the major cause of recurrences of hydatidosis, also called cystic echinococcosis (CE). Currently, many scolicidal agents are used for inactivation of the cyst contents. However, due to complications in the use of those agents, new and more-effective treatment options are urgently needed. The aim of this study was to investigate the in vitro efficacy of arsenic trioxide (ATO) against Echinococcus granulosus protoscolices. Protoscolices of E. granulosus were incubated in vitro with 2, 4, 6, and 8 μmol/liter ATO; viability of protoscolices was assessed daily by microscopic observation of movements and 0.1% eosin staining. A small sample from each culture was processed for scanning and transmission electron microscopy. ATO demonstrated a potent ability to kill protoscolices, suggesting that ATO may represent a new strategy in treating hydatid cyst echinococcosis. However, the in vivo efficacy and possible side effects of ATO need to be explored. PMID:26324279

  5. Arsenic trioxide negatively affects Echinococcus granulosus.

    PubMed

    Wang, Bo; Jiang, Yufeng; Wang, Zhuo; Li, Fangfang; Xing, Guoqiang; Peng, Xinyu; Zhang, Shijie; Lv, Hailong

    2015-11-01

    Spillage of cyst contents during surgery is the major cause of recurrences of hydatidosis, also called cystic echinococcosis (CE). Currently, many scolicidal agents are used for inactivation of the cyst contents. However, due to complications in the use of those agents, new and more-effective treatment options are urgently needed. The aim of this study was to investigate the in vitro efficacy of arsenic trioxide (ATO) against Echinococcus granulosus protoscolices. Protoscolices of E. granulosus were incubated in vitro with 2, 4, 6, and 8 μmol/liter ATO; viability of protoscolices was assessed daily by microscopic observation of movements and 0.1% eosin staining. A small sample from each culture was processed for scanning and transmission electron microscopy. ATO demonstrated a potent ability to kill protoscolices, suggesting that ATO may represent a new strategy in treating hydatid cyst echinococcosis. However, the in vivo efficacy and possible side effects of ATO need to be explored.

  6. Mortality experience in relation to a measured arsenic trioxide exposure.

    PubMed

    Pinto, S S; Enterline, P E; Henderson, V; Varner, M O

    1977-08-01

    This report examines the mortality experience of 527 men who retired from a copper smelter where they were exposed to airborne arsenic trioxide. Urinary arsenic values of all plant employees were determined in 1973, and the relative arsenic exposure in the various departments of the plant were determined. The relationship of airborne arsenic concentrations to urinary arsenic values was studied in a separate experiment, and the feasibility of using urinary arsenic values as a measure of arsenic exposure was established. The mortality experience of the cohort under study showed them to have a mortality 12.2% higher than was found for males of the same area at the same ages and in the same time period. The excess mortality was due chiefly to respiratory cancer. When the deaths were classified by total lifetime arsenic exposure, the respiratory cancer mortality was linearly related to the amount of exposure. The 1973 figures for arsenic exposure underestimated the exposure of the cohort group by a factor of possibly 10. Evidence was obtained which suggests that after removal from arsenic exposure, the risk of lung cancer declines. Certain of the data which are presented suggests there may be a threshold value for airborne arsenic trioxide exposure below which no adverse effects may be expected.

  7. Factors Determining Sensitivity and Resistance of Tumor Cells to Arsenic Trioxide

    PubMed Central

    Sertel, Serkan; Tome, Margaret; Briehl, Margaret M.; Bauer, Judith; Hock, Kai; Plinkert, Peter K.; Efferth, Thomas

    2012-01-01

    Previously, arsenic trioxide showed impressive regression rates of acute promyelocytic leukemia. Here, we investigated molecular determinants of sensitivity and resistance of cell lines of different tumor types towards arsenic trioxide. Arsenic trioxide was the most cytotoxic compound among 8 arsenicals investigated in the NCI cell line panel. We correlated transcriptome-wide microarray-based mRNA expression to the IC50 values for arsenic trioxide by bioinformatic approaches (COMPARE and hierarchical cluster analyses, Ingenuity signaling pathway analysis). Among the identified pathways were signaling routes for p53, integrin-linked kinase, and actin cytoskeleton. Genes from these pathways significantly predicted cellular response to arsenic trioxide. Then, we analyzed whether classical drug resistance factors may also play a role for arsenic trioxide. Cell lines transfected with cDNAs for catalase, thioredoxin, or the anti-apoptotic bcl-2 gene were more resistant to arsenic trioxide than mock vector transfected cells. Multidrug-resistant cells overexpressing the MDR1, MRP1 or BCRP genes were not cross-resistant to arsenic trioxide. Our approach revealed that response of tumor cells towards arsenic trioxide is multi-factorial. PMID:22590507

  8. Survival after a massive overdose of arsenic trioxide.

    PubMed

    Kim, Lawrence H C; Abel, Simon J C

    2009-03-01

    Arsenic poisoning remains a therapeutic challenge, and outcomes are often poor. An 18-year-old man deliberately ingested termiticide containing a massive dose of arsenic trioxide. Arsenic concentration was 6.3 micromol/L in serum on ICU Day 1, and 253 micromol/L in the first 24-hour urine sample, with a urinary arsenic/creatinine ratio of 84 200 micromol/mol. He was treated with the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA) (replaced by dimercaprol on Days 2-5) and required intensive support for multisystem organ failure, but recovered slowly. Nine weeks after the ingestion the only ongoing clinical issue was persistent but slowly improving peripheral neuropathy.

  9. [Two different clinical cases of acute arsenic trioxide intoxication].

    PubMed

    Magdalan, Jan; Smolarek, Małgorzata; Porebska, Barbara; Zawadzki, Marcin; Dyś, Piotr

    2007-01-01

    This paper describes two different cases of acute suicidal arsenic trioxide intoxication. Case no 1. A 38-year-old man, alcohol abuser, who ingested 4-5 g dental paste, which corresponds to 2.2-2.7 g of pure arsenic trioxide, developed gastritis with vomiting and abdominal pain, but without diarrhea. No cardiovascular collapse or renal failure were observed. The patient developed also symptoms of central nervous system injury (minor left paresis) and transient hepatic impairment. A head CT revealed no pathological changes in the brain. Hepatic disturbance recovered in a few days and the patient could be discharged on the 12 day. Case no 2. A 57-year-old man, who ingested few grams of pure arsenic developed vomiting, abdominal pain and severe diarrhea. Cardiovascular collapse as a result of intravascular volume depletion, vasodilatation and myocardial dysfunction was observed. The patient died on the first day of hospitalization. In both cases treatment included gastric lavage, BAL therapy, haemodialysis and supportive measures.

  10. Hyperoside enhances the suppressive effects of arsenic trioxide on acute myeloid leukemia cells

    PubMed Central

    Zhang, Feng; Zhu, Fang-Bing; Li, Jia-Jia; Zhang, Ping-Ping; Zhu, Jun-Feng

    2015-01-01

    Hyperoside (Hyp) is the chief component of some Chinese herbs which has anticancer effect and the present study is to identify whether it could enhance the anti leukemic properties of arsenic trioxide (As2O3) in acute myeloid leukemia (AML). We provide evidence on the concomitant treatment of HL-60 human AML cells with hyperoside potentiates As2O3-dependent induction of apoptosis. The activation of caspase-9, Bcl-2-associated agonist of cell death (BAD), p-BAD, p27 was assessed by Western blot. Results showed that hyperoside inhibited BAD from phosphorylating, reactivated caspase-9, and increased p27 levels. Importantly, hyperoside demonstrated its induction of autophagy effect by upregulation of LC-II in HL-60 AML cell line. Taken together, hyperoside may serve as a great candidate of concomitant treatment for leukemia; these effects were probably related to induction of autophagy and enhancing apoptosis-inducing action of As2O3. PMID:26629016

  11. Cytotoxicity patterns of arsenic trioxide exposure on HaCaT keratinocytes

    PubMed Central

    Udensi, Udensi K; Graham-Evans, Barbara E; Rogers, Christian; Isokpehi, Raphael D

    2011-01-01

    Background Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin are the most common outcomes of long-term, low-dose, chronic arsenic exposure. If the balance between keratinocyte proliferation, differentiation, and death is perturbed, pathologic changes of the epidermis may result, including psoriasis, atopic dermatitis, and certain forms of ichthyosis. Therefore, research investigations using in vitro human epidermal cells could help elucidate cellular and molecular processes in keratinocytes affected by arsenic. Data from such investigations could also provide the basis for developing cosmetic intervention for skin diseases caused by arsenic. Methods The viability of HaCaT keratinocyte cultures with or without prior exposure to low-dose arsenic trioxide was compared for varying concentrations of arsenic trioxide over a time course of 14 days because in untreated control cultures, approximately 2 weeks is required to complete cell differentiation. Long-term cultures were established by culturing HaCaT cells on collagen IV, and cells were subsequently exposed to 0 parts per million (ppm), 1 ppm, 5 ppm, 7.5 ppm, 10 ppm, and 15 ppm of arsenic trioxide. The percentages of viable cells as well as DNA damage after exposure were determined on Day 2, Day 5, Day 8, and Day 14. Results Using both statistical and visual analytics approaches for data analysis, we have observed a biphasic response at a 5 ppm dose with cell viability peaking on Day 8 in both chronic and acute exposures. Further, a low dose of 1 ppm arsenic trioxide enhanced HaCaT keratinocyte proliferation, whereas doses above 7.5 ppm inhibited growth. Conclusion The time course profiling of arsenic trioxide cytotoxicity using long-term HaCaT keratinocyte cultures presents an approach to modeling the human epidermal cellular responses to varying doses of arsenic trioxide treatment or exposure. A low dose of arsenic trioxide appears to aid cell growth but concomitantly disrupts the DNA

  12. Thermal behaviour of arsenic trioxide adsorbed on activated carbon.

    PubMed

    Cuypers, Frederic; De Dobbelaere, Christopher; Hardy, An; Van Bael, Marlies K; Helsen, Lieve

    2009-07-30

    The thermal stability and desorption of arsenic trioxide (As(2)O(3)) adsorbed on activated carbon (AC) was investigated as this phenomenon is expected to influence the arsenic release during low temperature pyrolysis of chromated copper arsenate (CCA) wood waste. Firstly, a thermogravimetric (TG) experiment with arsenolite, an allotropic form of As(2)O(3), was performed. The sample starts to sublime at temperatures lower than 200 degrees C with a sublimation peak temperature of 271 degrees C. Subsequently, TG experiments with samples of As(2)O(3) adsorbed on AC revealed that only very little (max. 6+/-3 wt%) As(2)O(3) was volatilized at temperatures below 280 degrees C, while still 41.6 (+/-5)wt% of the original arsenic concentration was retained at 440 degrees C and 28.5 (+/-3)wt% at 600 degrees C. The major arsenic volatilization occurred between 300 degrees C and 500 degrees C. The kinetic parameters of desorption, activation energy of desorption (E(d)) and pre-exponential factor (A), were determined by fitting an Arrhenius model to the experimental data, resulting in E(d)=69 kJ/mol, A=1.21 x 10(4)s(-1). It can be concluded that the adsorption of As(2)O(3) on AC can contribute to the thermal stabilisation of As(2)O(3). Consequently, during low temperature pyrolysis of CCA wood arsenic release may be prevented by adsorption of As(2)O(3) on the coal-type product formed during the thermal decomposition of the wood. PMID:19136209

  13. Severe Acute Axonal Neuropathy following Treatment with Arsenic Trioxide for Acute Promyelocytic Leukemia: a Case Report

    PubMed Central

    Kühn, Marcus; Sammartin, Kety; Nabergoj, Mitja; Vianello, Fabrizio

    2016-01-01

    Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide. PMID:27158436

  14. Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide.

    PubMed

    Lu, Jun; Chew, Eng-Hui; Holmgren, Arne

    2007-07-24

    Arsenic trioxide (ATO) is an effective cancer therapeutic drug for acute promyelocytic leukemia and has potential anticancer activity against a wide range of solid tumors. ATO exerts its effect mainly through elevated oxidative stress, but the exact molecular mechanism remains elusive. The thioredoxin (Trx) system comprising NADPH, thioredoxin reductase (TrxR), and Trx and the glutathione (GSH) system composed of NADPH, glutathione reductase, and GSH supported by glutaredoxin are the two electron donor systems that control cellular proliferation, viability, and apoptosis. Recently, the selenocysteine-dependent TrxR enzyme has emerged as an important molecular target for anticancer drug development. Here, we have discovered that ATO irreversibly inhibits mammalian TrxR with an IC(50) of 0.25 microM. Both the N-terminal redox-active dithiol and the C-terminal selenothiol-active site of reduced TrxR may participate in the reaction with ATO. The inhibition of MCF-7 cell growth by ATO was correlated with irreversible inactivation of TrxR, which subsequently led to Trx oxidation. Furthermore, the inhibition of TrxR by ATO was attenuated by GSH, and GSH depletion by buthionine sulfoximine enhanced ATO-induced cell death. These results strongly suggest that the ATO anticancer activity is by means of a Trx system-mediated apoptosis. Blocking cancer cell DNA replication and repair and induction of oxidative stress by the inhibition of both Trx and GSH systems are suggested as cancer chemotherapeutic strategies.

  15. Resveratrol protects against arsenic trioxide-induced nephrotoxicity by facilitating arsenic metabolism and decreasing oxidative stress.

    PubMed

    Yu, Meiling; Xue, Jiangdong; Li, Yijing; Zhang, Weiqian; Ma, Dexing; Liu, Lian; Zhang, Zhigang

    2013-06-01

    Arsenic trioxide (As(2)O(3)) is an environmental toxicant and a potent antineoplastic agent. Exposure to arsenic causes renal cancer. Resveratrol is a well-known polyphenolic compound that is reported to reduce As(2)O(3)-induced cardiotoxicity. The present study aimed to investigate the effect of resveratrol on As(2)O(3)-induced nephrotoxicity and arsenic metabolism. Chinese Dragon-Li cats were injected with 1 mg/kg As(2)O(3) on alternate days; resveratrol (3 mg/kg) was administered via the forearm vein 1 h before the As(2)O(3) treatment. On the sixth day, the cats were killed to determine the histological renal damage, renal function, the accumulation of arsenic, and antioxidant activities in the kidney. Urine samples were taken for arsenic speciation. In the resveratrol + As(2)O(3)-treated group, activities of glutathione peroxidase, catalase, and superoxide dismutase, the ratio of reduced glutathione to oxidized glutathione, the total arsenic concentrations, and the percentage of methylated arsenic in urine were significantly increased. The concentrations of renal malondialdehyde, reactive oxygen species, 8-hydroxydeoxyguanosine, serum creatinine, blood urea nitrogen, and renal arsenic accumulation were significantly decreased and reduced renal morphologic injury was observed compared with the As(2)O(3)-treated group. These results demonstrate that resveratrol could significantly scavenge reactive oxygen species, inhibit As(2)O(3)-induced oxidative damage, and significantly attenuate the accumulation of arsenic in renal tissues by facilitating As(2)O(3) metabolism. These data suggest that use of resveratrol as postremission therapy for acute promyelocytic leukemia as well as adjunctive therapy in patients with exposure to arsenic may decrease arsenic nephrotoxicity. PMID:23471352

  16. Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide.

    PubMed

    Unnikrishnan, D; Dutcher, J P; Varshneya, N; Lucariello, R; Api, M; Garl, S; Wiernik, P H; Chiaramida, S

    2001-03-01

    Arsenic trioxide is used in clinical trials in the treatment of relapsed and resistant cases of acute promyelocytic leukemia. Adverse effects from arsenic in these studies have been multisystemic. Arsenic is known to cause corrected QT-interval prolongation and T-wave changes, but the potential for serious ventricular arrhythmias is less well understood. Torsades de pointes, a form of ventricular tachycardia, has been reported with arsenic poisoning but not at therapeutic doses used in protocols for hematologic malignancies. We describe 3 patients in whom this arrhythmia developed while they were treated with arsenic trioxide. Early recognition of the arrhythmia or correction of contributory factors is important because arsenic induced ventricular arrhythmias are known to be resistant to most chemical methods and electrical cardioversion.

  17. Double-edged effects of arsenic compounds: anticancer and carcinogenic effects.

    PubMed

    Rehman, Kanwal; Naranmandura, Hua

    2013-12-01

    Although arsenic is known to cause cancers of lung, skin and kidney, arsenic trioxide (As2O3) has been recently recognized as one of the most effective novel anticancer agent for the treatment of acute promyelocytic leukemia (APL). These paradoxical effects of arsenic may be dose-dependent, associated with its distinctive metabolism, or correlated with its direct or indirect effects on different cellular pathways which may result in altered cellular functions. The basic mechanism through which As2O3 induces molecular remission in APL patients include direct targeting of PML and retinoic acid receptor alpha fusion protein (PML-RARα) by arsenic resulting in oncoprotein degradation leading to partial differentiation. Many in vitro studies have also indicated that the anticancer properties of As2O3 against non-APL blood cancers predominantly occur through induction of apoptotic pathway. Especially, release of cytochrome c or activation of the caspase cascades and apoptosis-related proteins by arsenic is thought to occur by directly targeting mitochondria. The mechanisms and the selective target sites that have been usually associated with the cytotoxic effects of arsenicals are discussed here with reference to their contribution towards the anticancer properties of arsenic. In this review we have particularly explained the in vivo or in vitro arsenic toxicity based on arsenic metabolic pathway and its different metabolites. These multiple effects and different selective target sites for arsenic and its metabolites emphasize the need for better understanding of paradoxical effects of arsenic which may provide the appropriate use of this agent in the treatment of various malignancies. PMID:24164099

  18. Double-edged effects of arsenic compounds: anticancer and carcinogenic effects.

    PubMed

    Rehman, Kanwal; Naranmandura, Hua

    2013-12-01

    Although arsenic is known to cause cancers of lung, skin and kidney, arsenic trioxide (As2O3) has been recently recognized as one of the most effective novel anticancer agent for the treatment of acute promyelocytic leukemia (APL). These paradoxical effects of arsenic may be dose-dependent, associated with its distinctive metabolism, or correlated with its direct or indirect effects on different cellular pathways which may result in altered cellular functions. The basic mechanism through which As2O3 induces molecular remission in APL patients include direct targeting of PML and retinoic acid receptor alpha fusion protein (PML-RARα) by arsenic resulting in oncoprotein degradation leading to partial differentiation. Many in vitro studies have also indicated that the anticancer properties of As2O3 against non-APL blood cancers predominantly occur through induction of apoptotic pathway. Especially, release of cytochrome c or activation of the caspase cascades and apoptosis-related proteins by arsenic is thought to occur by directly targeting mitochondria. The mechanisms and the selective target sites that have been usually associated with the cytotoxic effects of arsenicals are discussed here with reference to their contribution towards the anticancer properties of arsenic. In this review we have particularly explained the in vivo or in vitro arsenic toxicity based on arsenic metabolic pathway and its different metabolites. These multiple effects and different selective target sites for arsenic and its metabolites emphasize the need for better understanding of paradoxical effects of arsenic which may provide the appropriate use of this agent in the treatment of various malignancies.

  19. Metabolism of arsenic trioxide in acute promyelocytic leukemia cells.

    PubMed

    Khaleghian, Ali; Ghaffari, Seyed H; Ahmadian, Shahin; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

    2014-10-01

    Arsenic trioxide (As2O3) effectively induces complete clinical and molecular remissions in acute promyelocytic leukemia (APL) patients and triggers apoptosis in APL cells. The effect induced by As2O3 is also associated with extensive genomic-wide epigenetic changes with large-scale alterations in DNA methylation. We investigated the As2O3 metabolism in association with factors involved in the production of its methylated metabolites in APL-derived cell line, NB4. We used high performance liquid chromatography (HPLC) technique to detect As2O3 metabolites in NB4 cells. The effects of As2O3 on glutathione level, S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels were investigated. Also, we studied the expression levels of arsenic methyltransferase (AS3MT) and DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) by real-time PCR. Our results show that after As2O3 entry into the cell, it was converted into methylated metabolites, mono-methylarsenic (MMA) and dimethylarsenic (DMA). The glutathione (GSH) production was increased in parallel with the methylated metabolites formations. As2O3 treatment inhibited DNMTs (DNMT1, DNMT3a, and DNMT3b) in dose- and time-dependent manners. The SAH levels in As2O3-treated cells were increased; however, the SAM level was not affected. The present study shows that APL cell is capable of metabolizing As2O3. The continuous formation of intracellular methylated metabolites, the inhibition of DNMTs expression levels and the increase of SAH level by As2O3 biotransformation would probably affect the DNMTs-methylated DNA methylation in a manner related to the extent of DNA hypomethylation. Production of intracellular methylated metabolites and epigenetic changes of DNA methylation during As2O3 metabolism may contribute to the therapeutic effect of As2O3 in APL. PMID:24819152

  20. Potassium Bromate Assay by Redox Titrimetry Using Arsenic Trioxide.

    PubMed

    Smeller, Johanna M; Leigh, Stefan D

    2003-01-01

    Bromate, a disinfectant, is one of the analytes of interest in wastewater analysis. Environmental laboratories have a regulatory need for their measurements to be traceable to NIST standards. Bromate is not currently certified as a NIST Standard Reference Material (SRM). Therefore, a traceable assay of potassium bromate (KBrO3) is needed. KBrO3 was dissolved in water and assayed by redox titrimetry using arsenic trioxide (As2O3). A nominal (0.1 g) sample of As2O3 was dissolved in 10 mL of 5 mol/L sodium hydroxide. The solution was acidified with hydrochloric acid and about 95 % of the KBrO3 titrant was added gravimetrically. The end point was determined by addition of dilute (1:3) titrant using an automated titrator. The KBrO3 assay was determined to be 99.76 % ± 0.20 %. The expanded uncertainty considered the titrations of three independently prepared KBrO3 solutions.

  1. Arsenic trioxide rewires mantle cell lymphoma response to bortezomib.

    PubMed

    Zhao, Ling-Ling; Liu, Yuan-Fang; Peng, Li-Jun; Fei, Ai-Mei; Cui, Wen; Miao, Sheng-Chao; Hermine, Olivier; Gressin, Remy; Khochbin, Saadi; Chen, Sai-Juan; Wang, Jin; Mi, Jian-Qing

    2015-11-01

    Although most of the mantle cell lymphoma (MCL) patients initially responded well to bortezomib (BTZ), the dose-dependent toxicities have greatly limited the application of BTZ to MCL. To investigate the efficacy and mechanism of arsenic trioxide (ATO) with BTZ in inducing apoptosis of MCL cells, two MCL cell lines, along with primary cells from MCL patients (n = 4), were used. Additionally, the NOD-SCID mice xenograft model of Jeko-1 cells was established to study the anti-MCL mechanisms in an in vivo setting. ATO treatment highly improved BTZ capacity to inhibit proliferation and induce apoptosis of MCL cells. Furthermore, the interaction of Noxa and Mcl-1 leads Bak to release from Mcl-1 or from Bcl-xl, which could further activate Bak and Bax and then induce cell apoptosis. We also found that when lower doses of BTZ were used in combination with ATO, more effective proapoptotic effects in both the cell lines and the primary cells were obtained compared to the effects of BTZ used alone at higher doses. Simultaneously, the combination of these two drugs delayed the tumor growth in mice more effectively than BTZ alone. The cooperative anti-MCL effects of this combination therapy both in vitro and in vivo strongly provided a new strategy to the clinical treatment of MCL. PMID:26310857

  2. Interaction between arsenic trioxide (ATO) and human neutrophils.

    PubMed

    Binet, François; Chiasson, Sonia; Girard, Denis

    2011-05-01

    The cytotoxic effect of arsenic trioxide (ATO) is known to be mediated by its ability to induce cell apoptosis in a variety of cells, including neutrophils. More recently, we demonstrated that ATO induced several parameters involved in endoplasmic reticulum (ER) stress-induced neutrophil apoptosis but that caspase-4 was not involved. The aim of this study was to better understand how neutrophils are activated by ATO and to further demonstrate that ATO is an ER stressor. Human neutrophils were isolated from healthy blood donors and incubated in vitro in the presence or absence of ATO and several parameters were investigated. We found that ATO induced the expression of the proapoptotic GADD153 protein, a key player involved in ER stress-induced apoptosis, activated nuclear nuclear factor κB (NF-κB) DNA binding activities, and increased prostaglandine E2 (PGE2) production. Using an antibody array approach, we found that ATO increased the production of several cytokines, with interleukin 8 (IL-8) being the predominant one. We confirmed that ATO increased the production of IL-8 by enzyme-linked-immunosorbent assay (ELISA). Treatment with a caspase-4 inhibitor did not inhibit IL-8 production. The results of the present study further support the notion that ATO is an ER stressor and that, although its toxic effect is mediated by induction of apoptosis, this chemical also induced, in parallel, NF-κB activation, the production of PGE2 and several cytokines probably involved in other cell functions. Also, we conclude that the production of IL-8 is not induced by a caspase-4-dependent mechanism, suggesting that ATO-induced caspase-4 activation is involved in other as yet unidentified functions in human neutrophils.

  3. Morphine Attenuated the Cytotoxicity Induced by Arsenic Trioxide in H9c2 Cardiomyocytes.

    PubMed

    Amini-Khoei, Hossein; Hosseini, Mir-Jamal; Momeny, Majid; Rahimi-Balaei, Maryam; Amiri, Shayan; Haj-Mirzaian, Arya; Khedri, Mostafa; Jahanabadi, Samane; Mohammadi-Asl, Ali; Mehr, Shahram Ejtemaie; Dehpour, Ahmad Reza

    2016-09-01

    Arsenic trioxide (ATO) is an efficient drug for the treatment of the patients with acute promyelocytic leukemia (APL). Inhibition of proliferation as well as apoptosis, attenuation of migration, and induction of differentiation in tumor cells are the main mechanisms through which ATO acts against APL. Despite advantages of ATO in treatment of some malignancies, certain harmful side effects, such as cardiotoxicity, have been reported. It has been well documented that morphine has antioxidant, anti-apoptotic, and cytoprotective properties and is able to attenuate cytotoxicity. Therefore, in this study, we aimed to investigate the protective effects of morphine against ATO toxicity in H9c2 myocytes using multi-parametric assay including thiazolyl blue tetrazolium bromide (MTT) assay, reactive oxygen species (ROS) generation, caspase 3 activity, nuclear factor kappa B (NF-κB) phosphorylation assay, and expression of apoptotic markers. Our results showed that morphine (1 μM) attenuated cytotoxicity induced by ATO in H9c2 cells. Results of this study suggest that morphine may have protective properties in management of cardiac toxicity in patients who receive ATO as an anti-cancer treatment. PMID:26815588

  4. Arsenic trioxide-mediated growth inhibition in gallbladder carcinoma cells via down-regulation of Cyclin D1 transcription mediated by Sp1 transcription factor

    SciTech Connect

    Ai, Zhilong; Lu, Weiqi; Ton, Saixiong; Liu, Houbao; Sou, Tao; Shen, Zhenbin; Qin, Xinyu . E-mail: smc_jjh@yahoo.com.cn

    2007-08-31

    Gallbladder carcinoma (GBC), an aggressive and mostly lethal malignancy, is known to be resistant to a number of drug stimuli. Here, we demonstrated that arsenic trioxide inhibited the proliferation of gallbladder carcinoma in vivo and in vitro as well as the transcription of cell cycle-related protein Cyclin D1. And, Cyclin D1 overexpression inhibited the negative role of arsenic trioxide in cell cycle progression. We further explored the mechanisms by which arsenic trioxide affected Cyclin D1 transcription and found that the Sp1 transcription factor was down-regulated by arsenic trioxide, with a corresponding decrease in Cyclin D1 promoter activity. Taken together, these results suggested that arsenic trioxide inhibited gallbladder carcinoma cell proliferation via down-regulation of Cyclin D1 transcription in a Sp1-dependent manner, which provided a new mechanism of arsenic trioxide-involved cell proliferation and may have important therapeutic implications in gallbladder carcinoma patients.

  5. Effects of arsenic trioxide inhalation exposure on pulmonary antibacterial defenses in mice

    SciTech Connect

    Aranyi, C.; Bradof, J.N.; O'Shea, W.J.; Graham, J.A.; Miller, F.J.

    1985-01-01

    The effects of single and multiple (5 and 20) 3-h inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce particulate aerosols of 0. 4 micron mass median aerodynamic diameter. Aerosol mass concentration ranged from 125 to 1000 micrograms As/m3. Effects of the exposures were evaluated by determination of changes in susceptibility to experimentally induced streptococcal aerosol infection and in pulmonary bactericidal activity to /sup 35/S-labeled Klebsiella pneumoniae. Significant increases in mortality due to the infectious challenge and decreases in bactericidal activity were seen after single 3-h exposures to 270, 500, and 940 micrograms As/m3. Similarly, 5 or 20 multiple 3-h exposures to 500 micrograms As/m3 produced consistently significant increases in mortality and decreases in pulmonary bactericidal activity. At 125 or 250 micrograms As/m3, a decrease in bactericidal activity was seen only after 20 exposures to 250 micrograms/m3. Results from earlier studies with an arsenic-containing copper smelter dust were compared to these data. The possibility of the development of adaptation during multiple exposures to arsenic trioxide is also considered.

  6. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    SciTech Connect

    Wang, Hongtao; Gao, Peng; Zheng, Jie

    2014-09-05

    Highlights: • As{sub 2}O{sub 3} inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As{sub 2}O{sub 3} is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As{sub 2}O{sub 3}) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As{sub 2}O{sub 3} induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As{sub 2}O{sub 3} on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As{sub 2}O{sub 3} than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As{sub 2}O{sub 3} than HPV 16-positive CaSki and SiHa cells. After As{sub 2}O{sub 3} treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As{sub 2}O{sub 3} is a potential anticancer drug for cervical cancer.

  7. Arsenic trioxide and melarsoprol induce apoptosis in plasma cell lines and in plasma cells from myeloma patients.

    PubMed

    Rousselot, P; Labaume, S; Marolleau, J P; Larghero, J; Noguera, M H; Brouet, J C; Fermand, J P

    1999-03-01

    Recent data have renewed the interest for arsenic-containing compounds as anticancer agents. In particular, arsenic trioxide (As2O3) has been demonstrated to be an effective drug in the treatment of acute promyelocytic leukemia by inducing programmed cell death in leukemic cells both in vitro and in vivo. This prompted us to study the in vitro effects of As2O3 and of another arsenical derivative, the organic compound melarsoprol, on human myeloma cells and on the plasma cell differentiation of normal B cells. At pharmacological concentrations (10(-8) to 10(-6) mol/L), As2O3 and melarsoprol caused a dose- and time-dependent inhibition of survival and growth in myeloma cell lines that was, in some, similar to that of acute promyelocytic leukemia cells. Both arsenical compounds induced plasma cell apoptosis, as assessed by 4',6-diamidino-2-phenylindole staining, detection of phosphatidylserine at the cell surface using annexin V, and by the terminal deoxynucleotidyl transferase-mediated nick end labeling assay. As2O3 and melarsoprol also inhibited viability and growth and induced apoptosis in plasma-cell enriched preparations from the bone marrow or blood of myeloma patients. In nonseparated bone marrow samples, both arsenical compounds triggered death in myeloma cells while sparing most myeloid cells, as demonstrated by double staining with annexin V and CD38 or CD15 antibodies. In primary myeloma cells as in cell lines, interleukin 6 did not prevent arsenic-induced cell death or growth inhibition, and no synergistic effect was observed with IFN-alpha. In contrast to As2O3, melarsoprol only slightly reduced the plasma cell differentiation of normal B cells induced by pokeweed mitogen. Both pokeweed mitogen-induced normal plasma cells and malignant plasma cells showed a normal nuclear distribution of PML protein, which was disrupted by As2O3 but not by melarsoprol, suggesting that the two arsenical derivatives acted by different mechanisms. These results point to the

  8. Absence of prenatal developmental toxicity from inhaled arsenic trioxide in rats.

    PubMed

    Holson, J F; Stump, D G; Ulrich, C E; Farr, C H

    1999-09-01

    A review of the literature revealed no published inhalational developmental toxicity studies of arsenic performed according to modern regulatory guidelines and with exposure throughout gestation. In the present study, inorganic arsenic, as arsenic trioxide (As(+3), As2O3), was administered via whole-body inhalational exposure to groups of twenty-five Crl:CD(SD)BR female rats for six h per day every day, beginning fourteen days prior to mating and continuing throughout mating and gestation. Exposures were begun prior to mating in order to achieve a biological steady state of As(+3) in the dams prior to embryonal-fetal development. In a preliminary exposure range-finding study, half of the females that had been exposed to arsenic trioxide at 25 mg/m3 died or were euthanized in extremis. In the definitive study, target exposure levels were 0.3, 3.0, and 10.0 mg/m3. Maternal toxicity, which was determined by the occurrence of rales, a decrease in net body weight gain, and a decrease in food intake during pre-mating and gestational exposure, was observed only at the 10 mg/m3 exposure level. Intrauterine parameters (mean numbers of corpora lutea, implantation sites, resorptions and viable fetuses, and mean fetal weights) were unaffected by treatment. No treatment-related malformations or developmental variations were noted at any exposure level. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 3.0 mg/m3; the NOAEL for developmental toxicity was greater than or equal to 10 mg/m3, 760 times both the time-weighted average threshold limit value (TLV) and the permissible exposure limit (PEL) for humans. Based on the results of this study, we conclude that arsenic trioxide, when administered via whole-body inhalation to pregnant rats, is not a developmental toxicant.

  9. Melatonin enhances arsenic trioxide-induced cell death via sustained upregulation of Redd1 expression in breast cancer cells.

    PubMed

    Yun, Sun-Mi; Woo, Sang Hyeok; Oh, Sang Taek; Hong, Sung-Eun; Choe, Tae-Boo; Ye, Sang-Kyu; Kim, Eun-Kyu; Seong, Min Ki; Kim, Hyun-A; Noh, Woo Chul; Lee, Jin Kyung; Jin, Hyeon-Ok; Lee, Yun-Han; Park, In-Chul

    2016-02-15

    Melatonin is implicated in various physiological functions, including anticancer activity. However, the mechanism(s) of its anticancer activity is not well understood. In the present study, we investigated the combined effects of melatonin and arsenic trioxide (ATO) on cell death in human breast cancer cells. Melatonin enhanced the ATO-induced apoptotic cell death via changes in the protein levels of Survivin, Bcl-2, and Bax, thus affecting cytochrome c release from the mitochondria to the cytosol. Interestingly, we found that the cell death induced by co-treatment with melatonin and ATO was mediated by sustained upregulation of Redd1, which was associated with increased production of reactive oxygen species (ROS). Combined treatment with melatonin and ATO induced the phosphorylation of JNK and p38 MAP kinase downstream from Redd1 expression. Rapamycin and S6K1 siRNA enhanced, while activation of mTORC1 by transfection with TSC2 siRNA suppressed the cell death induced by melatonin and ATO treatment. Taken together, our findings suggest that melatonin enhances ATO-induced apoptotic cell death via sustained upregulation of Redd1 expression and inhibition of mTORC1 upstream of the activation of the p38/JNK pathways in human breast cancer cells. PMID:26607805

  10. Signal transduction pathways and transcription factors triggered by arsenic trioxide in leukemia cells

    SciTech Connect

    Sumi, Daigo; Shinkai, Yasuhiro; Kumagai, Yoshito

    2010-05-01

    Arsenic trioxide (As{sub 2}O{sub 3}) is widely used to treat acute promyelocytic leukemia (APL). Several lines of evidence have indicated that As{sub 2}O{sub 3} affects signal transduction and transactivation of transcription factors, resulting in the stimulation of apoptosis in leukemia cells, because some transcription factors are reported to associate with the redox condition of the cells, and arsenicals cause oxidative stress. Thus, the disturbance and activation of the cellular signaling pathway and transcription factors due to reactive oxygen species (ROS) generation during arsenic exposure may explain the ability of As{sub 2}O{sub 3} to induce a complete remission in relapsed APL patients. In this report, we review recent findings on ROS generation and alterations in signal transduction and in transactivation of transcription factors during As{sub 2}O{sub 3} exposure in leukemia cells.

  11. Protective effect of resveratrol on arsenic trioxide-induced nephrotoxicity in rats

    PubMed Central

    Zhang, Weiqian; Liu, Yan; Ge, Ming; Jing, Jiang; Chen, Yan; Jiang, Huijie; Yu, Hongxiang; Li, Ning

    2014-01-01

    BACKGROUD/OBEJECTIVES Arsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide (As2O3)-induced Male Wistar rats. MATERIALS/METHODS Adult rats received 3 mg/kg As2O3 (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv.) 1 h before As2O3 treatment. The plasma and homogenization enzymes associated with oxidative stress of rat kidneys were measured, the kidneys were examined histologically and trace element contents were assessed. RESULTS Rats treated with As2O3 had significantly higher oxidative stress and kidney arsenic accumulation; however, pretreatment with resveratrol reversed these changes. In addition, prior to treatment with resveratrol resulted in lower blood urea nitrogen, creatinine and insignificant renal tubular epithelial cell necrosis. Furthermore, the presence of resveratrol preserved the selenium content (0.805 ± 0.059 µg/g) of kidneys in rats treated with As2O3. However, resveratrol had no effect on zinc level in the kidney relative to As2O3-treated groups. CONCLUSIONS Our data show that supplementation with resveratrol alleviated nephrotoxicity by improving antioxidant capacity and arsenic efflux. These findings suggest that resveratrol has the potential to protect against kidney damage in populations exposed to arsenic. PMID:24741408

  12. Downregulation of thymidylate synthase and E2F1 by arsenic trioxide in mesothelioma.

    PubMed

    Lam, Sze-Kwan; Li, Yuan-Yuan; Zheng, Chun-Yan; Ho, James Chung-Man

    2015-01-01

    Malignant pleural mesothelioma is a global health issue. Arsenic trioxide (ATO) has been shown to suppress thymidylate synthase (TYMS) in lung adenocarcinoma and colorectal cancer, and induce apoptosis in acute promyelocytic leukemia. With TYMS as a putative therapeutic target, the effect of ATO in mesothelioma was therefore studied. A panel of 5 mesothelioma cell lines was used to study the effect of ATO on cell viability, protein expression, mRNA expression and TYMS activity by MTT assay, western blot, qPCR and tritium-release assay, respectively. The knockdown of TYMS and E2F1 was performed with a specific siRNA. Phosphatidylserine externalization and mitochondrial membrane depolarization were measured by Annexin V and JC-1 staining respectively. The in vivo effect of ATO was studied using a nude mouse xenograft model. Application of ATO demonstrated anticancer effects in the cell line model with clinically achievable concentrations. Downregulation of TYMS protein (except H226 cells and 1.25 µM ATO in H2052 cells) and mRNA expression (H28 cells), pRB1 (H28 cells) and E2F1 and TYMS activity (except H226 cells) were also evident. E2F1 knockdown decreased cell viability more significantly than TYMS knockdown. In general, thymidine kinase 1, ribonucleotide reductase M1, c-myc and skp2 were downregulated by ATO. p-c-Jun was downregulated in H28 cells while upregulated in 211H cells. Phosphatidylserine externalization, mitochondrial membrane depolarization, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bak and cleaved caspase-3 were observed. In the H226 xenograft model, the relative tumor growth was aborted, and E2F1 was downregulated while cleaved caspase-3 was elevated and localized to the nucleus in the ATO treatment group. ATO has potent antiproliferative and cytotoxic effects in mesothelioma in vitro and in vivo, partially mediated through E2F1 targeting (less effect through TYMS targeting). There is sound scientific evidence to support the

  13. Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

    PubMed Central

    2012-01-01

    Background Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO) in combination with sorafenib or fluorouracil (5-FU), in both hepatic tumor cells and stromal cells. Methods Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Results Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC50: 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC50: 11.8 μM in LX2; 9.9 μM in HepG2). In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr) drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. Conclusions ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC). PMID:22963400

  14. Comparative effects of single intraperitoneal or oral doses of sodium arsenate or arsenic trioxide during in utero development.

    PubMed

    Stump, D G; Holson, J F; Fleeman, T L; Nemec, M D; Farr, C H

    1999-11-01

    Numerous studies have suggested that single-day intraperitoneal (IP) injection of inorganic arsenic results in failure of neural tube closure and other malformations in rats, hamsters, and mice. Most of these studies involved treatment of limited numbers of animals with maternally toxic doses of arsenic (generally As(V)), without defining a dose-response relationship. In the present Good Laboratory Practice-compliant study, sodium arsenate (As(V)) was administered IP and arsenic trioxide (As(III)) was administered either IP or orally (by gavage) on gestational day 9 to groups of 25 mated Crl:CD(R)(SD)BR rats. Only at dose levels that caused severe maternal toxicity, including lethality, did IP injection of arsenic trioxide produce neural tube and ocular defects; oral administration of higher doses of arsenic trioxide caused some maternal deaths but no treatment-related fetal malformations. In contrast, IP injection of similar amounts of sodium arsenate (based on the molar amount of arsenic) caused mild maternal toxicity but a large increase in malformations, including neural tube, eye, and jaw defects. In summary, neural tube and craniofacial defects were observed after IP injection of both As(V) and As(III); however, no increase in malformations was seen following oral administration of As(III), even at maternally lethal doses. These results demonstrate that the frequently cited association between prenatal exposure to inorganic arsenic and malformations in laboratory animals is dependent on a route of administration that is not appropriate for human risk assessment.

  15. Mitigation of hepatotoxic effects of arsenic trioxide through omega-3 fatty acid in rats.

    PubMed

    Mathews, Varghese V; Paul, Mv Sauganth; Abhilash, M; Manju, Alex; Abhilash, S; Nair, R Harikumaran

    2014-10-01

    Arsenic trioxide (As(2)O(3)) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As(2)O(3)-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As(2)O(3) was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As(2)O(3). Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As(2)O(3). In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As(2)O(3) offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As(2)O(3)-induced hepatotoxicity.

  16. Effect of n-propylthiouracil or thyroxine on arsenic trioxide toxicity in the liver of rat.

    PubMed

    Allen, Tanu; Rana, Suresh Vir Singh

    2007-01-01

    Involvement of thyroid gland in the hepatotoxic manifestations of arsenic trioxide (As(III)) has been studied in rat. The effects of n-propylthiouracil (PTU) (a thyrotoxic compound) and L-thyroxine (a thyroid hormone) have been studied with reference to T(3) and T(4) values in the serum, arsenic concentration in the liver, Ca(2+) accumulation in the liver, aspartate transaminase, alanine transaminase and bilirubin values as the indicators of liver function, histopathological observations and finally the ultrastructural studies. It is concluded that hypothyroid condition protects against As(III) toxicity. Scavenging of reactive oxygen species (ROS) that significantly contribute in As(III) toxicity, by high intracellular concentration of reduced glutathione, as a consequence of PTU treatment is proposed as the plausible protective mechanism.

  17. Arsenic: a beneficial therapeutic poison - a historical overview.

    PubMed

    Thomas, Xavier; Troncy, Jacques

    2009-06-01

    Arsenicals have been used since ancient Greek and Roman civilizations and in the Far East as part of traditional Chinese medicine. In Western countries, they became a therapeutic mainstay for various ailments and malignancies in the 19th and early 20th centuries. Fowler's potassium bicarbonate-based solution of arsenic trioxide (As2O3)solution was the main treatment of chronic myeloid leukaemia until the 1930s. After a decline in the use of arsenic during the mid-20th century, arsenic trioxide was reintroduced as an anticancer agent after reports emerged from China of the success of an arsenic trioxide-containing herbal mixture for the treatment of acute promyelocytic leukaemia. Arsenic trioxide was first purified and used in controlled studies in China in the 1970s.Subsequently, randomised clinical trials performed in the United States led to FDA approval of arsenic trioxide in the treatment of patients with relapsed or refractory acute promyelocytic leukaemia.

  18. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    SciTech Connect

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.; Ballestas, Mary E.; Elmets, Craig A.; Robbins, David J.; Matalon, Sadis; Deshane, Jessy S.; Afaq, Farrukh; Bickers, David R.; Athar, Mohammad

    2013-11-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

  19. Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes

    PubMed Central

    Rebuzzini, Paola; Cebral, Elisa; Fassina, Lorenzo; Alberto Redi, Carlo; Zuccotti, Maurizio; Garagna, Silvia

    2015-01-01

    Chronic arsenic exposure is associated with increased morbidity and mortality for cardiovascular diseases. Arsenic increases myocardial infarction mortality in young adulthood, suggesting that exposure during foetal life correlates with cardiac alterations emerging later. Here, we investigated the mechanisms of arsenic trioxide (ATO) cardiomyocytes disruption during their differentiation from mouse embryonic stem cells. Throughout 15 days of differentiation in the presence of ATO (0.1, 0.5, 1.0 μM) we analysed: the expression of i) marker genes of mesoderm (day 4), myofibrillogenic commitment (day 7) and post-natal-like cardiomyocytes (day 15); ii) sarcomeric proteins and their organisation; iii) Connexin 43 and iv) the kinematics contractile properties of syncytia. The higher the dose used, the earlier the stage of differentiation affected (mesoderm commitment, 1.0 μM). At 0.5 or 1.0 μM the expression of cardiomyocyte marker genes is altered. Even at 0.1 μM, ATO leads to reduction and skewed ratio of sarcomeric proteins and to a rarefied distribution of Connexin 43 cardiac junctions. These alterations contribute to the dysruption of the sarcomere and syncytium organisation and to the impairment of kinematic parameters of cardiomyocyte function. This study contributes insights into the mechanistic comprehension of cardiac diseases caused by in utero arsenic exposure. PMID:26447599

  20. Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes.

    PubMed

    Rebuzzini, Paola; Cebral, Elisa; Fassina, Lorenzo; Alberto Redi, Carlo; Zuccotti, Maurizio; Garagna, Silvia

    2015-10-08

    Chronic arsenic exposure is associated with increased morbidity and mortality for cardiovascular diseases. Arsenic increases myocardial infarction mortality in young adulthood, suggesting that exposure during foetal life correlates with cardiac alterations emerging later. Here, we investigated the mechanisms of arsenic trioxide (ATO) cardiomyocytes disruption during their differentiation from mouse embryonic stem cells. Throughout 15 days of differentiation in the presence of ATO (0.1, 0.5, 1.0 μM) we analysed: the expression of i) marker genes of mesoderm (day 4), myofibrillogenic commitment (day 7) and post-natal-like cardiomyocytes (day 15); ii) sarcomeric proteins and their organisation; iii) Connexin 43 and iv) the kinematics contractile properties of syncytia. The higher the dose used, the earlier the stage of differentiation affected (mesoderm commitment, 1.0 μM). At 0.5 or 1.0 μM the expression of cardiomyocyte marker genes is altered. Even at 0.1 μM, ATO leads to reduction and skewed ratio of sarcomeric proteins and to a rarefied distribution of Connexin 43 cardiac junctions. These alterations contribute to the dysruption of the sarcomere and syncytium organisation and to the impairment of kinematic parameters of cardiomyocyte function. This study contributes insights into the mechanistic comprehension of cardiac diseases caused by in utero arsenic exposure.

  1. Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes.

    PubMed

    Rebuzzini, Paola; Cebral, Elisa; Fassina, Lorenzo; Alberto Redi, Carlo; Zuccotti, Maurizio; Garagna, Silvia

    2015-01-01

    Chronic arsenic exposure is associated with increased morbidity and mortality for cardiovascular diseases. Arsenic increases myocardial infarction mortality in young adulthood, suggesting that exposure during foetal life correlates with cardiac alterations emerging later. Here, we investigated the mechanisms of arsenic trioxide (ATO) cardiomyocytes disruption during their differentiation from mouse embryonic stem cells. Throughout 15 days of differentiation in the presence of ATO (0.1, 0.5, 1.0 μM) we analysed: the expression of i) marker genes of mesoderm (day 4), myofibrillogenic commitment (day 7) and post-natal-like cardiomyocytes (day 15); ii) sarcomeric proteins and their organisation; iii) Connexin 43 and iv) the kinematics contractile properties of syncytia. The higher the dose used, the earlier the stage of differentiation affected (mesoderm commitment, 1.0 μM). At 0.5 or 1.0 μM the expression of cardiomyocyte marker genes is altered. Even at 0.1 μM, ATO leads to reduction and skewed ratio of sarcomeric proteins and to a rarefied distribution of Connexin 43 cardiac junctions. These alterations contribute to the dysruption of the sarcomere and syncytium organisation and to the impairment of kinematic parameters of cardiomyocyte function. This study contributes insights into the mechanistic comprehension of cardiac diseases caused by in utero arsenic exposure. PMID:26447599

  2. Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells

    PubMed Central

    Kryeziu, Kushtrim; Pirker, Christine; Englinger, Bernhard; van Schoonhoven, Sushilla; Spitzwieser, Melanie; Mohr, Thomas; Körner, Wilfried; Weinmüllner, Regina; Tav, Koray; Grillari, Johannes; Cichna-Markl, Margit; Berger, Walter; Heffeter, Petra

    2016-01-01

    As an environmental poison, arsenic is responsible for many cancer deaths. Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to treat refractory acute promyelocytic leukemia (APL) and is intensively investigated for treatment of other cancer types. Noteworthy, cancer therapy is frequently hampered by drug resistance, which is also often associated with enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected cancer cells (A2780ATO) for the mechanisms underlying their enhanced tumorigenicity and aggressiveness. These cells were characterized by enhanced proliferation and spheroid growth as well as increased tumorigenicity of xenografts in SCID mice. Noteworthy, subsequent studies revealed that overexpression of Met receptor was the underlying oncogenic driver of these effects, as A2780ATO cells were characterized by collateral sensitivity against Met inhibitors. This finding was also confirmed by array comparative genomic hybridization (array CGH) and whole genome gene expression arrays, which revealed that Met overexpression by chronic ATO exposure was based on the transcriptional regulation via activation of AP-1. Finally, it was shown that treatment with the Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in vivo, indicating that targeting of Met presents a promising strategy for the treatment of Met-overexpressing tumors after either arsenic exposure or failure to ATO treatment. PMID:27036042

  3. Blockage of JNK pathway enhances arsenic trioxide-induced apoptosis in human keratinocytes

    SciTech Connect

    Huang, H.-S.; Liu, Z.-M.; Hong, D.-Y.

    2010-04-15

    Arsenic is well known as a carcinogen predisposing humans to some severe diseases and also as an effective medicine for treating acute promyelocytic leukemia, syphilis, and psoriasis. Multiple active mechanisms, including cell cycle arrest and apoptosis, have been proposed in therapy; however, the opposing effects of arsenic remain controversial. Our previous study found that arsenic trioxide (ATO)-induced activation of p21{sup WAF1/CIP1} (p21) led to A431 cell death through the antagonistic effects of the signaling of ERK1/2 and JNK1. In the current study, the inhibitory effects of JNK1 on ATO-induced p21 expression were explored. Over-expression of JNK1 in A431 cells could inhibit p21 expression, which was associated with HDAC1 and TGIF. Using the GST pull-down assay and fluorescence resonance energy transfer analysis, N-terminal domain (amino acids 1-108) of TGIF, critical to its binding with c-Jun, was found. Using reporter assays, requirement of the C-terminal domain (amino acids 138-272) of TGIF to suppress ATO-induced p21 expression was observed. Thus, the domains of TGIF that carried out its inhibitory effects on p21 were identified. Finally, treatment with JNK inhibitor SP600125 could enhance ATO-induced apoptosis of HaCaT keratinocytes by using flow cytometry.

  4. Erythema multiforme due to arsenic trioxide in a case of acute promyelocytic leukemia: A diagnostic challenge

    PubMed Central

    Badarkhe, Girish V.; Sil, Amrita; Bhattacharya, Sabari; Nath, Uttam Kumar; Das, Nilay Kanti

    2016-01-01

    Erythema multiforme (EM) is an acute, self-limited, Type IV hypersensitivity reactions associated with infections and drugs. In this case of acute promyelocytic leukemia, EM diagnosed during the induction phase was mistakenly attributed to vancomycin used to treat febrile neutropenia during that period. However, the occurrence of the lesions of EM again during the consolidation phase with arsenic trioxide (ATO) lead to a re-evaluation of the patient and both the Naranjo and World Health Organization-Uppsala Monitoring Centre scale showed the causality association as “probable.” The rash responded to topical corticosteroids and antihistamines. This rare event of EM being caused by ATO may be attributed to the genetic variation of methyl conjugation in the individual which had triggered the response, and the altered metabolic byproducts acted as a hapten in the subsequent keratinocyte necrosis. PMID:27114640

  5. Erythema multiforme due to arsenic trioxide in a case of acute promyelocytic leukemia: A diagnostic challenge.

    PubMed

    Badarkhe, Girish V; Sil, Amrita; Bhattacharya, Sabari; Nath, Uttam Kumar; Das, Nilay Kanti

    2016-01-01

    Erythema multiforme (EM) is an acute, self-limited, Type IV hypersensitivity reactions associated with infections and drugs. In this case of acute promyelocytic leukemia, EM diagnosed during the induction phase was mistakenly attributed to vancomycin used to treat febrile neutropenia during that period. However, the occurrence of the lesions of EM again during the consolidation phase with arsenic trioxide (ATO) lead to a re-evaluation of the patient and both the Naranjo and World Health Organization-Uppsala Monitoring Centre scale showed the causality association as "probable." The rash responded to topical corticosteroids and antihistamines. This rare event of EM being caused by ATO may be attributed to the genetic variation of methyl conjugation in the individual which had triggered the response, and the altered metabolic byproducts acted as a hapten in the subsequent keratinocyte necrosis. PMID:27114640

  6. A potentized homeopathic drug, Arsenicum Album 200, can ameliorate genotoxicity induced by repeated injections of arsenic trioxide in mice.

    PubMed

    Banerjee, P; Biswas, S J; Belon, P; Khuda-Bukhsh, A R

    2007-09-01

    Groundwater arsenic contamination has become a menacing global problem. No drug is available until now to combat chronic arsenic poisoning. To examine if a potentized homeopathic remedy, Arsenicum Album-200, can effectively combat chronic arsenic toxicity induced by repeated injections of Arsenic trioxide in mice, the following experimental design was adopted. Mice (Mus musculus) were injected subcutaneously with 0.016% arsenic trioxide at the rate of 1 ml/100 g body weight, at an interval of 7 days until they were killed at day 30, 60, 90 or 120 and were divided into three groups: (i) one receiving a daily dose of Arsenicum Album-200 through oral administration, (ii) one receiving the same dose of diluted succussed alcohol (Alcohol-200) and (iii) another receiving neither drug, nor succussed alcohol. The remedy or the placebo, as the case may be, was fed from the next day onwards after injection until the day before the next injection, and the cycle was repeated until the mice were killed. Two other control groups were also maintained: one receiving only normal diet, and the other receiving normal diet and succussed alcohol. Several toxicity assays, such as cytogenetical (chromosome aberrations, micronuclei, mitotic index, sperm head anomaly) and biochemical (acid and alkaline phosphatases, lipid peroxidation), were periodically made. Compared with controls, the drug fed mice showed reduced toxicity at statistically significant levels in respect of all the parameters studied, thereby indicating protective potentials of the homeopathic drug against chronic arsenic poisoning.

  7. Arsenic trioxide and reduced glutathione act synergistically to augment inhibition of thyroid peroxidase activity in vitro.

    PubMed

    Palazzolo, Dominic L; Ely, Emily A

    2015-05-01

    Thyroid peroxidase (TPO) is the enzyme involved in thyroid hormone synthesis. Arsenic trioxide (As2O3) is known to inhibit TPO activity in vitro. This inhibition is believed to occur when As2O3 binds to TPO's free sulfhydryl groups. Reduced glutathione (GSH) is also known to inhibit TPO activity in vitro. This inhibition may occur because GSH acts as a competitive substrate for hydrogen peroxide, or possibly reduce the oxidized form of iodide, requirements for TPO action. On the other hand, one could speculate that GSH reduces arsenic-induced TPO inhibition by interacting directly with arsenic or TPO, consequently limiting arsenic's ability to inhibit TPO activity. Since GSH is known to inhibit thyroid hormone synthesis while at the same time it is also known to be an important antioxidant preventing cellular damage induced by oxidative stress and protecting the thyroid gland from oxidative damage induced by arsenic, we wanted to determine if a combination of As2O3 and reduced GSH would either attenuate or augment the As2O3-induced inhibition on TPO activity. Using an in vitro system, TPO was assayed spectrophotometrically in the presence of As2O3 (0.01, 0.1, 1, and 10 ppm), GSH (0.1, 1, 5, and 10 ppm), and As2O3 (0.1 ppm) and GSH (0.01, 0.1, 1, or 10 ppm) combinations. Our results show that 0.1, 1.0, and 10 ppm As2O3 inhibit TPO activity. Similarly, 5 and 10 ppm GSH also inhibit TPO activity. When 0.1 ppm As2O3 (i.e., the lowest dose of arsenic able to partially inhibit TPO activity) is combined with 0.01, 0.1, 1.0, or 10 ppm GSH inhibition of in vitro TPO activity is augmented as indicated by complete inhibition of TPO. The mechanism of this augmentation and whether it translates to living systems remains unclear.

  8. Arsenic trioxide phosphorylates c-Fos to transactivate p21{sup WAF1/CIP1} expression

    SciTech Connect

    Liu Zimiao; Huang, H.-S.

    2008-12-01

    An infamous poison, arsenic also has been used as a drug for nearly 2400 years; in recently years, arsenic has been effective in the treatment of acute promyelocytic leukemia. Increasing evidence suggests that opposite effects of arsenic trioxide (ATO) on tumors depend on its concentrations. For this reason, the mechanisms of action of the drug should be elucidated, and it should be used therapeutically only with extreme caution. Previously, we demonstrated the opposing effects of ERK1/2 and JNK on p21{sup WAF1/CIP1} (p21) expression in response to ATO in A431 cells. In addition, JNK phosphorylates c-Jun (Ser{sup 63/73}) to recruit TGIF/HDAC1 to suppress p21 gene expression. Presently, we demonstrated that a high concentration of ATO sustains ERK1/2 phosphorylation, and increases c-Fos biosynthesis and stability, which enhances p21 gene expression. Using site-directed mutagenesis, a DNA affinity precipitation assay, and functional assays, we demonstrated that phosphorylation of the C-terminus of c-Fos (Thr{sup 232}, Thr{sup 325}, Thr{sup 331}, and Ser{sup 374}) plays an important role in its binding to the p21 promoter, and in conjunction with N-terminus phosphorylation of c-Fos (Ser{sup 70}) to transactivate p21 promoter expression. In conclusion, a high concentration of ATO can sustain ERK1/2 activation to enhance c-Fos expression, then dimerize with dephosphorylated c-Jun (Ser{sup 63/73}) and recruit p300/CBP to the Sp1 sites (- 84/- 64) to activate p21 gene expression in A431 cells.

  9. Therapeutic Potential of Delivering Arsenic Trioxide into HPV-Infected Cervical Cancer Cells Using Liposomal Nanotechnology

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoyan; Li, Dong; Ghali, Lucy; Xia, Ruidong; Munoz, Leonardo P.; Garelick, Hemda; Bell, Celia; Wen, Xuesong

    2016-02-01

    Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 μm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double-immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status.

  10. Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced apoptosis in K562 cells.

    PubMed

    Song, Li-Li; Tu, Yao-Yao; Xia, Li; Wang, Wei-Wei; Wei, Wei; Ma, Chun-Min; Wen, Dong-Hua; Lei, Hu; Xu, Han-Zhang; Wu, Ying-Li

    2014-01-01

    Despite considerable efficacy of arsenic trioxide (As2O3) in acute promyelocytic leukemia (APL) treatment, other non-APL leukemias, such as chronic myeloid leukemia (CML), are less sensitive to As2O3 treatment. However, the underlying mechanism is not well understood. Here we show that relative As2O3-resistant K562 cells have significantly lower ROS levels than As2O3-sensitive NB4 cells. We compared the expression of several antioxidant enzymes in these two cell lines and found that peroxiredoxin 1/2/6 and catalase are expressed at high levels in K562 cells. We further investigated the possible role of peroxirdoxin 1/2/6 and catalase in determining the cellular sensitivity to As2O3. Interestingly, knockdown of peroxiredoxin 1/2/6 did not increase the susceptibility of K562 cells to As2O3. On the contrary, knockdown of catalase markedly enhanced As2O3-induced apoptosis. In addition, we provide evidence that overexpression of BCR/ABL cannot increase the expression of PRDX 1/2/6 and catalase. The current study reveals that the functional role of antioxidant enzymes is cellular context and treatment agents dependent; targeting catalase may represent a novel strategy to improve the efficacy of As2O3 in CML treatment.

  11. Arsenic trioxide disrupts glioma stem cells via promoting PML degradation to inhibit tumor growth

    PubMed Central

    Zhou, Wenchao; Cheng, Lin; Shi, Yu; Ke, Susan Q.; Huang, Zhi; Fang, Xiaoguang; Chu, Cheng-wei; Xie, Qi; Bian, Xiu-wu; Rich, Jeremy N.; Bao, Shideng

    2015-01-01

    Glioblastoma multiforme (GBM) is the most lethal brain tumor. Tumor relapse in GBM is inevitable despite maximal therapeutic interventions. Glioma stem cells (GSCs) have been found to be critical players in therapeutic resistance and tumor recurrence. Therapeutic drugs targeting GSCs may significantly improve GBM treatment. In this study, we demonstrated that arsenic trioxide (As2O3) effectively disrupted GSCs and inhibited tumor growth in the GSC-derived orthotopic xenografts by targeting the promyelocytic leukaemia (PML). As2O3 treatment induced rapid degradation of PML protein along with severe apoptosis in GSCs. Disruption of the endogenous PML recapitulated the inhibitory effects of As2O3 treatment on GSCs both in vitro and in orthotopic tumors. Importantly, As2O3 treatment dramatically reduced GSC population in the intracranial GBM xenografts and increased the survival of mice bearing the tumors. In addition, As2O3 treatment preferentially inhibited cell growth of GSCs but not matched non-stem tumor cells (NSTCs). Furthermore, As2O3 treatment or PML disruption potently diminished c-Myc protein levels through increased poly-ubiquitination and proteasome degradation of c-Myc. Our study indicated a potential implication of As2O3 in GBM treatment and highlighted the important role of PML/c-Myc axis in the maintenance of GSCs. PMID:26510911

  12. Optimization of combination therapy of arsenic trioxide and fractionated radiotherapy for malignant glioma

    SciTech Connect

    Ning Shoucheng; Knox, Susan J. . E-mail: sknox@stanford.edu

    2006-06-01

    Purpose: The primary objective was to optimize the combined treatment regimen using arsenic trioxide (ATO) and fractionated radiotherapy for the treatment of malignant glioma. Methods and Materials: Nude mice with human glioma xenograft tumors were treated with fractionated local tumor radiation of 250 cGy/fraction/day and 5 mg/kg ATO for 5-10 days. Results: Time course experiments demonstrated that maximal tumor growth delay occurred when ATO was administered between 0 and 4 h after radiation. The combination treatment of ATO and radiation synergistically inhibited tumor growth and produced a tumor growth delay time of 13.2 days, compared with 1.4 days and 6.5 days for ATO and radiation alone (p < 0.01), respectively. The use of concurrent therapy of radiation and ATO initially, followed by ATO as maintenance therapy, was superior to the use of preloading with ATO before combined therapy and produced a tumor growth delay time of 22.7 days as compared with 11.7 days for the ATO preloading regimen (p < 0.01). The maintenance dose of ATO after concurrent therapy was effective and important for continued inhibition of tumor growth. Conclusions: The combined use of fractionated radiation and ATO is effective for the treatment of glioma xenograft tumors. ATO was most effective when administered 0-4 h after radiation without pretreatment with ATO. These results have important implications for the optimization of treatment regimen using ATO and fractionated radiotherapy for the treatment of brain tumors.

  13. 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.

  14. Arsenic trioxide disrupts glioma stem cells via promoting PML degradation to inhibit tumor growth.

    PubMed

    Zhou, Wenchao; Cheng, Lin; Shi, Yu; Ke, Susan Q; Huang, Zhi; Fang, Xiaoguang; Chu, Cheng-wei; Xie, Qi; Bian, Xiu-wu; Rich, Jeremy N; Bao, Shideng

    2015-11-10

    Glioblastoma multiforme (GBM) is the most lethal brain tumor. Tumor relapse in GBM is inevitable despite maximal therapeutic interventions. Glioma stem cells (GSCs) have been found to be critical players in therapeutic resistance and tumor recurrence. Therapeutic drugs targeting GSCs may significantly improve GBM treatment. In this study, we demonstrated that arsenic trioxide (As2O3) effectively disrupted GSCs and inhibited tumor growth in the GSC-derived orthotopic xenografts by targeting the promyelocytic leukaemia (PML). As2O3 treatment induced rapid degradation of PML protein along with severe apoptosis in GSCs. Disruption of the endogenous PML recapitulated the inhibitory effects of As2O3 treatment on GSCs both in vitro and in orthotopic tumors. Importantly, As2O3 treatment dramatically reduced GSC population in the intracranial GBM xenografts and increased the survival of mice bearing the tumors. In addition, As2O3 treatment preferentially inhibited cell growth of GSCs but not matched non-stem tumor cells (NSTCs). Furthermore, As2O3 treatment or PML disruption potently diminished c-Myc protein levels through increased poly-ubiquitination and proteasome degradation of c-Myc. Our study indicated a potential implication of As2O3 in GBM treatment and highlighted the important role of PML/c-Myc axis in the maintenance of GSCs. PMID:26510911

  15. Endothelial to mesenchymal transition contributes to arsenic-trioxide-induced cardiac fibrosis

    PubMed Central

    Zhang, Yong; Wu, Xianxian; Li, Yang; Zhang, Haiying; Li, Zhange; Zhang, Ying; Zhang, Longyin; Ju, Jiaming; Liu, Xin; Chen, Xiaohui; Glybochko, Peter V.; Nikolenko, Vladimir; Kopylov, Philipp; Xu, Chaoqian; Yang, Baofeng

    2016-01-01

    Emerging evidence has suggested the critical role of endothelial to mesenchymal transition (EndMT) in fibrotic diseases. The present study was designed to examine whether EndMT is involved in arsenic trioxide (As2O3)-induced cardiac fibrosis and to explore the underlying mechanisms. Cardiac dysfunction was observed in rats after exposure to As2O3 for 15 days using echocardiography, and the deposition of collagen was detected by Masson’s trichrome staining and electron microscope. EndMT was indicated by the loss of endothelial cell markers (VE-cadherin and CD31) and the acquisition of mesenchymal cell markers (α-SMA and FSP1) determined by RT-PCR at the mRNA level and Western blot and immunofluorescence analysis at the protein level. In the in-vitro experiments, endothelial cells acquired a spindle-shaped morphology accompanying downregulation of the endothelial cell markers and upregulation of the mesenchymal cell markers when exposed to As2O3. As2O3 activated the AKT/GSK-3β/Snail signaling pathway, and blocking this pathway with PI3K inhibitor (LY294002) abolished EndMT in As2O3-treated endothelial cells. Our results highlight that As2O3 is an EndMT-promoting factor during cardiac fibrosis, suggesting that targeting EndMT is beneficial for preventing As2O3-induced cardiac toxicity. PMID:27671604

  16. Heat shock protein inhibitors, 17-DMAG and KNK437, enhance arsenic trioxide-induced mitotic apoptosis

    SciTech Connect

    Wu Yichen; Yen Wenyen; Lee, T.-C. Yih, L.-H.

    2009-04-15

    Arsenic trioxide (ATO) has recently emerged as a promising therapeutic agent in leukemia because of its ability to induce apoptosis. However, there is no sufficient evidence to support its therapeutic use for other types of cancers. In this study, we investigated if, and how, 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG), an antagonist of heat shock protein 90 (HSP90), and KNK437, a HSP synthesis inhibitor, potentiated the cytotoxic effect of ATO. Our results showed that cotreatment with ATO and either 17-DMAG or KNK437 significantly increased ATO-induced cell death and apoptosis. siRNA-mediated attenuation of the expression of the inducible isoform of HSP70 (HSP70i) or HSP90{alpha}/{beta} also enhanced ATO-induced apoptosis. In addition, cotreatment with ATO and 17-DMAG or KNK437 significantly increased ATO-induced mitotic arrest and ATO-induced BUBR1 phosphorylation and PDS1 accumulation. Cotreatment also significantly increased the percentage of mitotic cells with abnormal mitotic spindles and promoted metaphase arrest as compared to ATO treatment alone. These results indicated that 17-DMAG or KNK437 may enhance ATO cytotoxicity by potentiating mitotic arrest and mitotic apoptosis possibly through increased activation of the spindle checkpoint.

  17. 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

  18. Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma.

    PubMed

    Boehme, Karen A; Zaborski, Julian J; Riester, Rosa; Schweiss, Sabrina K; Hopp, Ulrike; Traub, Frank; Kluba, Torsten; Handgretinger, Rupert; Schleicher, Sabine B

    2016-02-01

    Rhabdomyosarcomas (RMS) are soft tissue tumours treated with a combination of surgery and chemotherapy. However, mortality rates remain high in case of recurrences and metastatic disease due to drug resistance and failure to undergo apoptosis. Therefore, innovative approaches targeting specific signalling pathways are urgently needed. We analysed the impact of different hedgehog (Hh) pathway inhibitors on growth and survival of six RMS cell lines using MTS assay, colony formation assay, 3D spheroid cultures, flow cytometry and western blotting. Especially the glioma-associated oncogene family (GLI) inhibitor arsenic trioxide (ATO) effectively reduced viability as well as clonal growth and induced cell death in RMS cell lines of embryonal, alveolar and sclerosing, spindle cell subtype, whereas normal skeletal muscle cells were hardly compromised by ATO. Combination of ATO with itraconazole potentiated the reduction of colony formation and spheroid size. These results show that ATO is a promising substance for treatment of relapsed and refractory RMS by directly targeting GLI transcription factors. The combination with itraconazole or other chemotherapeutic drugs has the opportunity to enforce the treatment efficiency of resistant and recurrent RMS.

  19. Interaction between arsenic trioxide and human primary cells: emphasis on human cells of myeloid origin.

    PubMed

    Binet, François; Antoine, Francis; Girard, Denis

    2009-03-01

    Arsenic trioxide (As(2)O(3); ATO) is considered to be one of the most potent drugs in cancer chemotherapy and is highly effective in the treatment of acute promyelocytic leukemia (APL). It is well established that treatment of APL patients with ATO is associated with the disappearance of the PML-RARalpha fusion transcript, the characteristic APL gene product of the chromosomal translocation t(15;17). Although its mode of action is still not fully understood, ATO is known to induce cell apoptosis via generation of reactive oxygen species and activation of caspases. Several reports have indicated that ATO acts principally by inducing cell apoptosis not only in APL, but in a variety of non-APL cells including myeloma cells, chronic myeloid leukemia cells and cells of immune origin, including B or T lymphocytes, macrophages and, more recently, neutrophils. There is an increasing amount of data, including some from our laboratory, concerning the interaction between ATO and human primary cells. The focus of this review will be to cover the role of ATO in human immune primary cells with special emphasis on cells of myeloid origin.

  20. Arsenic trioxide induces endoplasmic reticulum stress-related events in neutrophils.

    PubMed

    Binet, François; Chiasson, Sonia; Girard, Denis

    2010-04-01

    We recently reported that the endoplasmic reticulum (ER)-induced cell pathway of apoptosis is operational in human neutrophils and that some ER stressors can accelerate this process. Recent data suggest that arsenic trioxide (As(2)O(3) or ATO), may also act as an ER stressor. The aims of the present study were to elucidate if other ER stress-related events occur in ATO-induced neutrophils, and to determine the role of caspase-4 in the proapoptotic activity of ATO. We found that ATO induced ubiquitination of proteins, and increased calcium concentration and gene expression of calcineurin in neutrophils. In addition to caspase-4, activities of caspase-3, -8 and -9 were increased by ATO. The processing of caspase-4 was reversed by a caspase-8 inhibitor, indicating that caspase-4 activation requires the action of upstream initiator components, questioning on the role of caspase-4 in ATO-induced ER stress-mediated cell apoptosis. Using caspase-4 deficient THP-1 cells, we demonstrated that the proapoptotic effect of ATO was similar to that of control caspase-4-positive cells. We conclude that ATO is an ER stressor that can induce cell apoptosis by a mechanism which does not require caspase-4. In addition, we conclude that caspase-4 activation in ATO-induced neutrophils could be involved in functions other than apoptosis.

  1. Retinoic acid and arsenic trioxide trigger degradation of mutated NPM1, resulting in apoptosis of AML cells.

    PubMed

    El Hajj, Hiba; Dassouki, Zeina; Berthier, Caroline; Raffoux, Emmanuel; Ades, Lionel; Legrand, Olivier; Hleihel, Rita; Sahin, Umut; Tawil, Nadim; Salameh, Ala; Zibara, Kazem; Darwiche, Nadine; Mohty, Mohamad; Dombret, Hervé; Fenaux, Pierre; de Thé, Hugues; Bazarbachi, Ali

    2015-05-28

    Nucleophosmin-1 (NPM1) is the most frequently mutated gene in acute myeloid leukemia (AML). Addition of retinoic acid (RA) to chemotherapy was proposed to improve survival of some of these patients. Here, we found that RA or arsenic trioxide synergistically induce proteasomal degradation of mutant NPM1 in AML cell lines or primary samples, leading to differentiation and apoptosis. NPM1 mutation not only delocalizes NPM1 from the nucleolus, but it also disorganizes promyelocytic leukemia (PML) nuclear bodies. Combined RA/arsenic treatment significantly reduced bone marrow blasts in 3 patients and restored the subnuclear localization of both NPM1 and PML. These findings could explain the proposed benefit of adding RA to chemotherapy in NPM1 mutant AMLs, and warrant a broader clinical evaluation of regimen comprising a RA/arsenic combination.

  2. Effective targeting of chronic myeloid leukemia initiating activity with the combination of arsenic trioxide and interferon alpha.

    PubMed

    El Eit, Rabab M; Iskandarani, Ahmad N; Saliba, Jessica L; Jabbour, Mark N; Mahfouz, Rami A; Bitar, Nizar M A; Ayoubi, Hanadi R El; Zaatari, Ghazi S; Mahon, Francois-Xavier; De Thé, Hugues B; Bazarbachi, Ali A; Nasr, Rihab R

    2014-02-15

    Imatinib is the standard of care in chronic meloid leukemia (CML) therapy. However, imatinib is not curative since most patients who discontinue therapy relapse indicating that leukemia initiating cells (LIC) are resistant. Interferon alpha (IFN) induces hematologic and cytogenetic remissions and interestingly, improved outcome was reported with the combination of interferon and imatinib. Arsenic trioxide was suggested to decrease CML LIC. We investigated the effects of arsenic and IFN on human CML cell lines or primary cells and the bone marrow retroviral transduction/transplantation murine CML model. In vitro, the combination of arsenic and IFN inhibited proliferation and activated apoptosis. Importantly, arsenic and IFN synergistically reduced the clonogenic activity of primary bone marrow cells derived from CML patients. Finally, in vivo, combined interferon and arsenic treatment, but not single agents, prolonged the survival of primary CML mice. Importantly, the combination severely impaired engraftment into untreated secondary recipients, with some recipients never developing the disease, demonstrating a dramatic decrease in CML LIC activity. Arsenic/IFN effect on CML LIC activity was significantly superior to that of imatinib. These results support further exploration of this combination, alone or with imatinib aiming at achieving CML eradication rather than long-term disease control. PMID:23934954

  3. Effective targeting of chronic myeloid leukemia initiating activity with the combination of arsenic trioxide and interferon alpha.

    PubMed

    El Eit, Rabab M; Iskandarani, Ahmad N; Saliba, Jessica L; Jabbour, Mark N; Mahfouz, Rami A; Bitar, Nizar M A; Ayoubi, Hanadi R El; Zaatari, Ghazi S; Mahon, Francois-Xavier; De Thé, Hugues B; Bazarbachi, Ali A; Nasr, Rihab R

    2014-02-15

    Imatinib is the standard of care in chronic meloid leukemia (CML) therapy. However, imatinib is not curative since most patients who discontinue therapy relapse indicating that leukemia initiating cells (LIC) are resistant. Interferon alpha (IFN) induces hematologic and cytogenetic remissions and interestingly, improved outcome was reported with the combination of interferon and imatinib. Arsenic trioxide was suggested to decrease CML LIC. We investigated the effects of arsenic and IFN on human CML cell lines or primary cells and the bone marrow retroviral transduction/transplantation murine CML model. In vitro, the combination of arsenic and IFN inhibited proliferation and activated apoptosis. Importantly, arsenic and IFN synergistically reduced the clonogenic activity of primary bone marrow cells derived from CML patients. Finally, in vivo, combined interferon and arsenic treatment, but not single agents, prolonged the survival of primary CML mice. Importantly, the combination severely impaired engraftment into untreated secondary recipients, with some recipients never developing the disease, demonstrating a dramatic decrease in CML LIC activity. Arsenic/IFN effect on CML LIC activity was significantly superior to that of imatinib. These results support further exploration of this combination, alone or with imatinib aiming at achieving CML eradication rather than long-term disease control.

  4. Antitumor efficacy of DMSA modified Fe3O4 magnetic nanoparticles combined with arsenic trioxide and adriamycin in Raji cells.

    PubMed

    Cai, Xiaohui; Cai, Xiaohui; Wang, Chunling; Chen, Baoan; Hua, Weijun; Shen, Fei; Yu, Liang; He, Zhengmei; Shi, Yuye; Chen, Yue; Xia, Guohua; Bao, Wen; Zhang, Yu; Wang, Xuemei

    2014-02-01

    The objective of the present study was to investigate the anticancer efficacy of dimercaptosuccinic acid modified iron oxide (DMSA-Fe3O4) magnetic nanoparticles (MNPs) combined with arsenic trioxide (As2O3) and doxorubicin (ADM) in non-Hodgkin's lymphoma (NHL) cell line (Raji cells). The growth inhibition rate of Raji cells was determined by MTT assay. Characteristics of DMSA-Fe3O4 MNPs and distribution of nanoparticles taken up by Raji cells were observed under a transmission electron microscopy (TEM). Further, apoptosis of cells and intracellular concentration of ADM were detected by flow cytometry (FCM). DAPI staining was used to view apoptotic cellular morphology. Subsequently, transcription and protein expression levels of bcl-2, NFKB, survivin, bax, p53 and caspase-3 were determined by reverse transciptase polymerase chain reaction (RT-PCR) and Western blotting analysis, respectively. The results of MTT assay indicated that the inhibition of Raji cells by the combined form of ADM and As2O3 was significantly higher than either ADM or As2O3 alone. However, ADM-As2O3 MNPs proved superior over all other groups. TEM observation revealed that the majority of MNPs were quasi-spherical with an average diameter of about 18 nm and the MNPs taken up by cells were located in the endosome vesicles of cytoplasm. The apoptotic rate and accumulation of intracellular ADM in ADM-As2O3 MNPs group were significantly higher than those in control, ADM, As2O3 and ADM+As2O3, groups. In addition, DAPI staining of Raji cells from ADM-As,O3 MNPs group clearly exhibited more morphological changes (severe structural alterations) than other groups. Moreover, transcription and protein expression of bcl-2, NFKB, survivin, bax, p53 and caspase-3 of Raji cells were regulated at the most remarkable extent in ADM-As2O3, MNPs group as compared with other groups. These findings suggest that the antitumor efficacy of the combination of novel ADM-As2O3, MNPs on Raji cells would be a promising

  5. Differential binding of monomethylarsonous acid compared to arsenite and arsenic trioxide with zinc finger peptides and proteins.

    PubMed

    Zhou, Xixi; Sun, Xi; Mobarak, Charlotte; Gandolfi, A Jay; Burchiel, Scott W; Hudson, Laurie G; Liu, Ke Jian

    2014-04-21

    Arsenic is an environmental toxin that enhances the carcinogenic effect of DNA-damaging agents, such as ultraviolet radiation and benzo[a]pyrene. Interaction with zinc finger proteins has been shown to be an important molecular mechanism for arsenic toxicity and cocarcinogenesis. Arsenicals such as arsenite, arsenic trioxide (ATO), and monomethylarsonous acid (MMA(III)) have been reported to interact with cysteine residues of zinc finger domains, but little is known about potential differences in their selectivity of interaction. Herein we analyzed the interaction of arsenite, MMA(III), and ATO with C2H2, C3H1, and C4 configurations of zinc fingers using UV-vis, cobalt, fluorescence, and mass spectrometry. We observed that arsenite and ATO both selectively bound to C3H1 and C4 zinc fingers, while MMA(III) interacted with all three configurations of zinc finger peptides. Structurally and functionally, arsenite and ATO caused conformational changes and zinc loss on C3H1 and C4 zinc finger peptide and protein, respectively, whereas MMA(III) changed conformation and displaced zinc on all three types of zinc fingers. The differential selectivity was also demonstrated in zinc finger proteins isolated from cells treated with these arsenicals. Our results show that trivalent inorganic arsenic compounds, arsenite and ATO, have the same selectivity and behavior when interacting with zinc finger proteins, while methylation removes the selectivity. These findings provide insights on the molecular mechanisms underlying the differential effects of inorganic versus methylated arsenicals, as well as the role of in vivo arsenic methylation in arsenic toxicity and carcinogenesis.

  6. Effects of freshwater exposure to arsenic trioxide on the parr-smolt transformation of coho salmon (Oncorhynchus kisutch)

    USGS Publications Warehouse

    Nichols, J.W.; Wedemeyer, G.A.; Mayer, F.L.; Dickhoff, Walton W.; Gregory, S.V.; Yasutake, W.T.; Smith, S.D.

    1984-01-01

    The effects of chronic (6 months) exposure to arsenic trioxide in fresh water on the Parr-smolt transformation of coho salmon (Oncorhynchus kisutch) were evaluated. Exposure to 300 μg As/L (as As2O3) appeared to delay the onset of the normal increase in plasma thyroxine concentration and cause a transient reduction of gill Na+,K+-ATPase activity. Fish exposed to 300 μg As/L also migrated to the sea less successfully than did nonexposed smolts, but there were no effects on the survival and growth of smolts held in 28‰ salt water for 6 months.

  7. Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: an useful salvage therapy.

    PubMed

    Huan, S Y; Yang, C H; Chen, Y C

    2000-07-01

    Arsenic trioxide (As2O3) was recently identified as a very potent agent against acute promyelocytic leukemia (APL). Intravenous infusion of 10 mg As2O3 daily for one to two months can induce significant complete remission (CR) of APL, and there is no cross drug-resistance between As2O3 and other antileukemic agents, including all-trans retinoic acid (ATRA). The CR rate of relapsed and/or refractory APL patients who received As2O3 treatment ranged from 52.3% to 93.3%. The median duration to CR ranged from 38 to 51 days, with accumulative As2O3 dosage of 340-430 mg. Although most adverse reactions of As2O3 treatment were tolerable, certain infrequent but severe toxicities related to As2O3 were observed, including renal failure, hepatic damage, cardiac arrhythmia and chronic neuromuscular degeneration, which should be monitored carefully. As2O3 can induce partial differentiation and subsequent apoptosis of APL cells through degradation of wild type PML and PML/RAR alpha chimeric proteins and possible anti-mitochondrial effects. Like the treatment of ATRA in APL, early relapses from As2O3 treatment within a few months were not infrequently seen, indicating that rapid emerging resistance to As2O3 can occur. Nevertheless, the PML/RAR alpha fusion protein was reported to disappear in some APL patients who received As2O3, and who might earn long-survival. However, the follow-up is still too short to draw the conclusion. Intriguingly, it has been shown that As2O3 can also induce apoptosis of other non-APL tumor cells with clinical achievable concentrations. However, the detailed molecular mechanisms are not yet fully understood. Further studies regarding to the pharmacological characters, clinical efficacies, toxicities, apoptogenic mechanisms, and spectrum of anti-tumor activity of As2O3 are warranted.

  8. Anticancer Activity of Small Molecule and Nanoparticulate Arsenic(III) Complexes

    PubMed Central

    Swindell, Elden P.; Hankins, Patrick L.; Chen, Haimei; Miodragović, Ðenana U.; O'Halloran, Thomas V.

    2014-01-01

    Starting in ancient China and Greece, arsenic-containing compounds have been used in the treatment of disease for over 3000 years. They were used for a variety of diseases in the 20th century, including parasitic and sexually transmitted illnesses. A resurgence of interest in the therapeutic application of arsenicals has been driven by the discovery that low doses of a 1% aqueous solution of arsenic trioxide (i.e. arsenous acid) leads to complete remission of certain types of leukemia. Since FDA approval of arsenic trioxide (As2O3) for treatment of acute promyelocytic leukemia (APL) in 2000, it has become a front line therapy in this indication. There are currently over 100 active clinical trials involving inorganic arsenic or organoarsenic compounds registered with the FDA for the treatment of cancers. New generations of inorganic and organometallic arsenic compounds with enhanced activity or targeted cytotoxicity are being developed to overcome some of the shortcomings of arsenic therapeutics, namely short plasma half-lives and narrow therapeutic window. PMID:24147771

  9. A facile route to core-shell nanoparticulate formation of arsenic trioxide for effective solid tumor treatment

    NASA Astrophysics Data System (ADS)

    Zhang, Zongjun; Liu, Hanyu; Zhou, Hualu; Zhu, Xianglong; Zhao, Zhenghuan; Chi, Xiaoqin; Shan, Hong; Gao, Jinhao

    2016-02-01

    Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a ``one-pot'' method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity (57.9 wt%) and a prolonged pH-responsive releasing profile, which is crucial to increase the drug concentration at tumor sites and improve the drug efficacy. Based on these unique features, the nanodrugs significantly inhibit the growth of solid tumors without adverse side effects. Therefore, we anticipate that the arsenic-based nanodrugs generated by this facile synthetic route may be a powerful and alternative strategy for solid tumor therapy.Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a ``one-pot'' method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity

  10. Have all-trans retinoic acid and arsenic trioxide replaced all-trans retinoic acid and anthracyclines in APL as standard of care.

    PubMed

    Iland, Harry J; Wei, Andrew; Seymour, John F

    2014-03-01

    Until recently, the standard of care in the treatment of APL has involved the combination of all-trans retinoic acid with anthracycline-based chemotherapy during both induction and consolidation. Additionally, the intensity of consolidation chemotherapy has evolved according to a universally accepted relapse-risk stratification algorithm based on the white cell and platelet counts at presentation. That standard of care is being challenged by the increasing incorporation of arsenic trioxide into front-line treatment protocols, based on two complementary observations. The first is the undoubted anti-leukaemic activity of arsenic trioxide as shown in the relapsed and refractory setting, and in the initial management of low- and intermediate-risk patients. The second is an improved understanding of the action of both all-trans retinoic acid and arsenic trioxide in mediating APL cell eradication, with increasing recognition that PML-RARA fusion protein degradation rather than direct induction of terminal differentiation is the primary mechanism for their ability to eliminate leukaemia initiating cells. As a result, we believe the standard of care for initial therapy in APL is shifting towards an all-trans retinoic acid plus arsenic trioxide-based approach, with additional chemotherapy reserved for patients with high-risk disease. PMID:24907016

  11. A facile route to core-shell nanoparticulate formation of arsenic trioxide for effective solid tumor treatment.

    PubMed

    Zhang, Zongjun; Liu, Hanyu; Zhou, Hualu; Zhu, Xianglong; Zhao, Zhenghuan; Chi, Xiaoqin; Shan, Hong; Gao, Jinhao

    2016-02-21

    Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a "one-pot" method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity (57.9 wt%) and a prolonged pH-responsive releasing profile, which is crucial to increase the drug concentration at tumor sites and improve the drug efficacy. Based on these unique features, the nanodrugs significantly inhibit the growth of solid tumors without adverse side effects. Therefore, we anticipate that the arsenic-based nanodrugs generated by this facile synthetic route may be a powerful and alternative strategy for solid tumor therapy.

  12. Activity of Nanobins Loaded with Cisplatin and Arsenic Trioxide in Primary and Metastatic Breast Cancer

    NASA Astrophysics Data System (ADS)

    Swindell, Elden Peter, III

    Despite recent advances in breast cancer screening and detection, the disease is still a leading cause of death for women of all ages. Young, African-American women are disproportionally affected with a type of breast cancer, triple-negative breast cancer, which is particularly difficult to treat and has the worst prognosis of any breast cancer subtype. These tumors often spread to the lungs, liver, bones and brains of patients, which is ultimately fatal. This dissertation presents results from a series of in vivo and in vitro experiments that investigate the clinical utility of a novel nanoparticulate formulation of cisplatin and arsenic trioxide, NB(Pt,As) for treating primary and metastatic triple-negative breast cancer. These nanobins consist of a solid, crystalline metal nanoparticle surrounded by a lipid bilayer with 80-90 nm diameter. This drug payload is extremely stable, and so NB(Pt,As) is extremely well tolerated in mice. Furthermore, NB(Pt,As) is effective in two different mouse models of breast cancer, one of primary tumor growth an another of lung metastases. A discovery presented here, that thiol containing compounds are required for drug release, may explain these seemingly incongruous results. The large amount of intracellular thiol can trigger drug release, while the low concentration of free thiols in blood is insufficient to cause drug release. To improve the treatment of brain tumors with this unique drug, we added transferrin to the surface of the nanobin using copper-catalyzed "click" chemistry, which preserves protein activity. The addition of transferrin to the nanobins enables 10 fold greater uptake in the brains of mice treated with the transferrin-targeted nanobins Tf-NB(Pt,A) compared to NB(Pt,As). By penetrating the blood brain barrier, the Tf-NB(Pt,As) was able to reduce breast cancer metastases in the brains of mice, whereas NB(Pt,As) had no effect. Taken together, these results demonstrate the intricate balance of drug release

  13. hsa-miR-203 enhances the sensitivity of leukemia cells to arsenic trioxide.

    PubMed

    He, Jin-Hua; Li, Yu-Min; Li, Yu-Guang; Xie, Xing-Yi; Wang, Li; Chun, Shun-Yi; Cheng, Wu-Jia

    2013-05-01

    The aim of this study was to investigate the effect of a eukaryotic expression vector expressing hsa-miR-203 on the sensitivity of K562 leukemia cells to arsenic trioxide (ATO) and the possible mechanism of action. The eukaryotic expression vector expressing the hsa-miR-203 plasmid (PmiR-203) was transfected into K562 cells using Lipofectamine 2000. bcr/abl 3' untranslated region (UTR) and bcr/abl mutated 3'UTR dual luciferase report vectors (psi-CHECK-2) were used to validate the regulation of bcr/abl by miR-203. The inhibitory effects of ATO and PmiR-203, used singly or in combination, on cell proliferation were detected by MTT assay. Apoptosis of the K562 cells was detected by flow cytometry using double-staining with Annexin V and propidium iodide (PI). The activities of caspase-3 and caspase-9 were detected by a colorimetric method and the cytochrome c protein levels were detected by western blotting. When used in combination with PmiR-203, the IC50 of ATO was reduced from 6.49 to 2.45 μg/ml and the sensitivity of cells to ATO increased 2.64-fold. In addition, PmiR-203 and ATO caused growth inhibition, apoptosis and G1-phase arrest in K562 cells. Furthermore, PmiR-203 significantly promoted ATO-mediated growth inhibition and apoptosis, affecting the G1 phase. JC-1 fluorescent staining revealed that the membrane potential of the mitochondria had changed. The activities of caspase-3 and caspase-9 increased, the expression levels of cytochrome c were upregulated and the expression level of bcr/abl mRNA was significantly suppressed. Furthermore, the dual-luciferase reporter vector, containing tandem miR-203 binding sites from the bcr/abl 3'UTR, demonstrated that bcr/abl was directly regulated by miR-203. PmiR-203 sensitized K562 leukemia cells to ATO by inducing apoptosis and downregulating bcr/ abl gene levels. The induction of apoptosis may occur through the mitochondrial pathway. The combination of ATO and PmiR-203 presents therapeutic potential for chronic

  14. Ebb-and-flow of macroautophagy and chaperone-mediated autophagy in Raji cells induced by starvation and arsenic trioxide.

    PubMed

    Li, Cai-Li; Wei, Hu-Lai; Chen, Jing; Wang, Bei; Xie, Bei; Fan, Lin-Lan; Li, Lin-Jing

    2014-01-01

    Autophagy is crucial in the maintenance of homeostasis and regenerated energy of mammalian cells. Macroautophagy and chaperone-mediated autophagy(CMA) are the two best-identified pathways. Recent research has found that in normal cells, decline of macroautophagy is appropriately parallel with activation of CMA. However, whether it is also true in cancer cells has been poorly studied. Here we focused on cross-talk and conversion between macroautophagy and CMA in cultured Burkitt lymphoma Raji cells when facing serum deprivation and exposure to a toxic compound, arsenic trioxide. The results showed that both macroautophagy and CMA were activated sequentially instead of simultaneously in starvation-induced Raji cells, and macroautophagy was quickly activated and peaked during the first hours of nutrition deprivation, and then gradually decreased to near baseline. With nutrient deprivation persisted, CMA progressively increased along with the decline of macroautophagy. On the other hand, in arsenic trioxide-treated Raji cells, macroautophagy activity was also significantly increased, but CMA activity was not rapidly enhanced until macroautophagy was inhibited by 3-methyladenine, an inhibitor. Together, we conclude that cancer cells exhibit differential responses to diverse stressor-induced damage by autophagy. The sequential switch of the first-aider macroautophagy to the homeostasis-stabilizer CMA, whether active or passive, might be conducive to the adaption of cancer cells to miscellaneous intracellular or extracellular stressors. These findings must be helpful to understand the characteristics, compensatory mechanisms and answer modes of different autophagic pathways in cancer cells, which might be very important and promising to the development of potential targeting interventions for cancer therapies via regulation of autophagic pathways. PMID:25081691

  15. Immunotoxicity and biodistribution analysis of arsenic trioxide in C57Bl/6 mice following a 2-week inhalation exposure

    SciTech Connect

    Burchiel, Scott W.; Mitchell, Leah A.; Lauer, Fredine T.; Sun Xi; McDonald, Jacob D.; Hudson, Laurie G.; Liu Kejian

    2009-12-15

    In these studies the immunotoxicity of arsenic trioxide (ATO, As{sub 2}O{sub 3}) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 h per day) at concentrations of 50 mug/m{sup 3} and 1 mg/m{sup 3}. A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 mug/g tissue following the 1 mg/m{sup 3} exposures. No spleen cell cytotoxicity was observed at either of the two exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 mug/m{sup 3} and 1 mg/m{sup 3} exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents.

  16. Azidothymidine hinders arsenic trioxide-induced apoptosis in acute promyelocytic leukemia cells by induction of p21 and attenuation of G2/M arrest.

    PubMed

    Hassani, Saeed; Ghaffari, Seyed H; Zaker, Farhad; Mirzaee, Rohellah; Mardani, Hajar; Bashash, Davood; Zekri, Ali; Yousefi, Meysam; Zaghal, Azam; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

    2013-09-01

    To enhance anticancer efficacy of the arsenic trioxide (ATO), the combination of ATO and azidothymidine (AZT), with convergence anti-telomerase activity, were examined on acute promyelocytic leukemia (APL) cell line, NB4. In spite of an induction of apoptosis by both drugs separately and a synergistic effect of them on hTERT down-regulation and telomerase inhibition, the ATO-induced cytotoxicity was reduced when it was used in combination with AZT. AZT attenuated the ATO effects on viability, metabolic activity, DNA synthesis, and apoptosis. These observations, despite the deflection from the main goal of this study, dedicate an especial opportunity to elucidate the importance of some of the mechanisms that have been suggested by which ATO induces apoptosis. Cell cycle distribution, ROS level, and caspase-3 activation analyses suggest that AZT reduced the ATO-induced cytotoxic effect possibly via relative induction and diminution of cells accumulated in (G1, S) and (G2/M) phase, respectively, as well as through attenuation of ROS generation and subsequent caspase-3 inhibition. QRT-PCR assay revealed that induction of p21expression by the combined AZT/ATO compared to ATO alone could be a reason for the relative decline of cells accumulation in G2/M and the increase of cells in G1 and S phases. Therefore, the G2/M arrest and ROS generation are likely principle mediators for the ATO-induced apoptosis and can be used as a guide to design rational combinatorial strategies involving ATO and agents with G2/M arrest or ROS generation capacity to intensify ATO-induced apoptosis.

  17. Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells

    PubMed Central

    Zeng, Yingjian; Weng, Guangyang; Fan, Jiaxin; Li, Zhangqiu; Wu, Jianwei; Li, Yuanming; Zheng, Rong; Xia, Pingfang; Guo, Kunyuan

    2016-01-01

    Low response, treatment-related complications and relapse due to the low sensitivity of myelodysplastic syndrome (MDS) and leukemia stem cells (LSCs) or pre-LSCs to arsenic trioxide (ATO), represent the main problems following treatment with ATO alone in patients with MDS. To solve these problems, a chemosensitization agent can be applied to increase the susceptibility of these cells to ATO. Curcumin (CUR), which possesses a wide range of anticancer activities, is a commonly used chemosensitization agent for various types of tumors, including hematopoietic malignancies. In the present study, we investigated the cytotoxic effects and potential mechanisms in MDS-SKM-1 and leukemia stem-like KG1a cells treated with CUR and ATO alone or in combination. CUR and ATO exhibited growth inhibition detected by MTT assays and apoptosis analyzed by Annexin V/PI analyses in both SKM-1 and KG1a cells. Apoptosis of SKM-1 and KG1a cells determined by Annexin V/PI was significantly enhanced in the combination groups compared with the groups treated with either agent alone. Further evaluation was performed by western blotting for two hallmark markers of apoptosis, caspase-3 and cleaved-PARP. Co-treatment of the cells with CUR and ATO resulted in significant synergistic effects. In SKM-1 and KG1a cells, 31 and 13 proteins analyzed by protein array assays were modulated, respectively. Notably, survivin protein expression levels were downregulated in both cell lines treated with CUR alone and in combination with ATO, particularly in the latter case. Susceptibility to apoptosis was significantly increased in SKM-1 and KG1a cells treated with siRNA-survivin and ATO. These results suggested that CUR increased the sensitivity of SKM-1 and KG1a cells to ATO by downregulating the expression of survivin. PMID:27430728

  18. Arsenic-Based Drugs: From Fowler's Solution to Modern Anticancer Chemotherapy

    NASA Astrophysics Data System (ADS)

    Gibaud, Stéphane; Jaouen, Gérard

    Although arsenic is a poison and has a predominantly unfavorable reputation, it has been used as pharmaceutical agent since the first century BC. In 1786, Thomas Fowler reported the effects of arsenic in the cure of agues, remittent fevers, and periodic headaches. From this time on and despite abusive use, some interesting indications began to appear for trypanosomiasis, syphilis, and blood diseases. The first significant organoarsenical drug (atoxyl) was synthesized by Pierre Antoine Béchamp in 1859 by chemically reacting arsenic acid with aniline but additional experimentations on the properties of arsenic led Paul Ehrlich, the founder of chemotherapy, to the discovery of salvarsan in 1910. From the Second World War, Ernst A.H. Friedheim greatly improved the treatment of trypanosomiasis by melaminophenyl arsenicals. Until the 1990s some organoarsenicals were used for intestinal parasite infections but carcinogenic effects were displayed and all the drugs have been withdrawn in USA, in Europe, and elsewhere. In 2003, arsenic trioxide (Trisenox®) was re-introduced for the treatment of very specific hematological malignancies.

  19. Cytotoxicity of arsenic trioxide is enhanced by (-)-epigallocatechin-3-gallate via suppression of ferritin in cancer cells

    SciTech Connect

    Lee, Te-Chang; Cheng, I-Cheng; Shue, Jun-Jie; Wang, T.C.

    2011-01-01

    Arsenic trioxide (ATO) treatment is a useful therapy against human acute promyelocytic leukemia (APL), however, it concomitantly brings potential adverse consequences including serious side effect, human carcinogenicity and possible development of resistance. This investigation revealed that those problems might be relaxed by simultaneous application with (-)-epigallocatechin-3-gallate (EGCG), one of the major components from green tea. EGCG significantly lowered down the ATO concentration required for an effective control of APL cells, HL-60. The simultaneous treatment of ATO with EGCG induced a mitochondria-dependent apoptosis in HL-60 cells significantly, which accounted for more than 70% of the cell death in the treatment. The mechanism of apoptosis induction was elucidated. EGCG in HL-60 cells acted as a pro-oxidant enhancing intracellular hydrogen peroxide significantly. ATO, on the other hand, induced heme oxygenase-1 (HO-1) to catalyze heme degradation, thereby provided ferrous iron for EGCG-induced hydrogen peroxide to precede Fenton reaction, which in turn generated deleterious reactive oxygen species to damage cell. In addition, EGCG inhibited expression of ferritin, which supposedly to sequester harmful ferrous iron, thereby augmented the occurrence of Fenton reaction. This investigation also provided evidence that ATO, since mainly acted to induce HO-1 in simultaneous treatment with EGCG, could be replaced by other HO-1 inducer with much less human toxicity. Furthermore, several of our preliminary investigations revealed that the enhanced cytotoxicity induced by combining heme degradation and Fenton reaction is selectively toxic to malignant but not non-malignant cells.

  20. Arsenic trioxide inhibits accelerated allograft rejection mediated by alloreactive CD8(+) memory T cells and prolongs allograft survival time.

    PubMed

    Li, Chun; Guan, Tianjun; Gao, Chang; Lin, Yingying; Yan, Guoliang; Zhu, Maoshu; Lv, Chongshan; Xia, Junjie; Qi, Zhongquan

    2015-09-01

    CD8(+) memory T (Tm) cells are a significant barrier to transplant tolerance induction in alloantigen-primed recipients, and are insensitive to existing clinical immunosuppressants. Here, we studied the inhibition of CD8(+) Tm cells by arsenic trioxide (As2O3) for the first time. Alloantigen-primed CD8(+) Tm cells were transferred to T cell immunodeficient nude mice. The mice were subjected to heart allotransplantation, and treated with As2O3. The transplant survival time was determined, and the inhibitory effects of As2O3 on CD8(+) Tm cell-mediated immune rejection were assessed through serological studies and inspection of the transplanted heart and lymphoid organs. We found that As2O3 treatment prolonged the mean survival time of the graft and reduced the number of CD8(+) Tm cells in the spleen and lymph nodes. The expression of the genes encoding interleukin (IL)-2, and IFN-γ was reduced, while expression of IL-10 and transforming growth factor-β was increased in the transplant. Our findings show that As2O3 treatment inhibits allograft rejection mediated by alloreactive CD8(+) Tm cells in the mouse heart transplantation model.

  1. Arsenic trioxide-based therapy of relapsed acute promyelocytic leukemia: registry results from the European LeukemiaNet.

    PubMed

    Lengfelder, E; Lo-Coco, F; Ades, L; Montesinos, P; Grimwade, D; Kishore, B; Ramadan, S M; Pagoni, M; Breccia, M; Huerta, A J G; Nloga, A M; González-Sanmiguel, J D; Schmidt, A; Lambert, J-F; Lehmann, S; Di Bona, E; Cassinat, B; Hofmann, W-K; Görlich, D; Sauerland, M-C; Fenaux, P; Sanz, M

    2015-05-01

    In 2008, a European registry of relapsed acute promyelocytic leukemia was established by the European LeukemiaNet. Outcome data were available for 155 patients treated with arsenic trioxide in first relapse. In hematological relapse (n=104), 91% of the patients entered complete hematological remission (CR), 7% had induction death and 2% resistance, 27% developed differentiation syndrome and 39% leukocytosis, whereas no death or side effects occurred in patients treated in molecular relapse (n=40). The rate of molecular (m)CR was 74% in hematological and 62% in molecular relapse (P=0.3). All patients with extramedullary relapse (n=11) entered clinical and mCR. After 3.2 years median follow-up, the 3-year overall survival (OS) and cumulative incidence of second relapse were 68% and 41% in hematological relapse, 66% and 48% in molecular relapse and 90 and 11% in extramedullary relapse, respectively. After allogeneic or autologous transplantation in second CR (n=93), the 3-year OS was 80% compared with 59% without transplantation (n=55) (P=0.03). Multivariable analysis demonstrated the favorable prognostic impact of first remission duration ⩾1.5 years, achievement of mCR and allogeneic or autologous transplantation on OS of patients alive after induction (P=0.03, P=0.01, P=0.01) and on leukemia-free survival (P=0.006, P<0.0001, P=0.003), respectively. PMID:25627637

  2. The Coadministration of N-Acetylcysteine Ameliorates the Effects of Arsenic Trioxide on the Male Mouse Genital System.

    PubMed

    da Silva, Raquel Frenedoso; Borges, Cibele dos Santos; Villela E Silva, Patrícia; Missassi, Gabriela; Kiguti, Luiz Ricardo Almeida; Pupo, André Sampaio; Barbosa Junior, Fernando; Anselmo-Franci, Janete Aparecida; Kempinas, Wilma De Grava

    2016-01-01

    Arsenic trioxide (As2O3) has shown effectiveness in treatment of leukemia but is also associated with reproductive toxicity. Since remediation with N-acetylcysteine (NAC) may mitigate the adverse effects caused by exposure, we assessed the effects of As2O3 and its potential reversibility after exposure cessation or coadministration of NAC. Animals received 0.3 or 3.0 mg/Kg/day of As2O3 subcutaneously and 40 mM of NAC in tap water. As2O3 treatment impaired spermatogenesis and sperm motility and decreased seminal vesicle weight and testosterone serum levels; after suspension of treatment, these parameters remained altered. When NAC was administered, animals showed improvement in sperm parameters and seminal vesicle weight. In vitro epididymal contractility was increased in As2O3-treated animals. We concluded that As2O3 is toxic to the male mouse genital system by compromising sperm quality and quantity; these effects persisted even after suspension of the treatment. However, the coadministration of NAC ameliorates the harmful effects of the drug on the male genital system. PMID:26839632

  3. The Coadministration of N-Acetylcysteine Ameliorates the Effects of Arsenic Trioxide on the Male Mouse Genital System

    PubMed Central

    da Silva, Raquel Frenedoso; Borges, Cibele dos Santos; Villela e Silva, Patrícia; Kiguti, Luiz Ricardo Almeida; Pupo, André Sampaio; Barbosa Junior, Fernando; Anselmo-Franci, Janete Aparecida; Kempinas, Wilma De Grava

    2016-01-01

    Arsenic trioxide (As2O3) has shown effectiveness in treatment of leukemia but is also associated with reproductive toxicity. Since remediation with N-acetylcysteine (NAC) may mitigate the adverse effects caused by exposure, we assessed the effects of As2O3 and its potential reversibility after exposure cessation or coadministration of NAC. Animals received 0.3 or 3.0 mg/Kg/day of As2O3 subcutaneously and 40 mM of NAC in tap water. As2O3 treatment impaired spermatogenesis and sperm motility and decreased seminal vesicle weight and testosterone serum levels; after suspension of treatment, these parameters remained altered. When NAC was administered, animals showed improvement in sperm parameters and seminal vesicle weight. In vitro epididymal contractility was increased in As2O3-treated animals. We concluded that As2O3 is toxic to the male mouse genital system by compromising sperm quality and quantity; these effects persisted even after suspension of the treatment. However, the coadministration of NAC ameliorates the harmful effects of the drug on the male genital system. PMID:26839632

  4. Effect of glucose in mice after acute experimental poisoning with arsenic trioxide (As2O3).

    PubMed

    Reichl, F X; Szinicz, L; Kreppel, H; Fichtl, B; Forth, W

    1990-01-01

    Carbohydrate depletion (glucose and glycogen) was reported to be a major problem in acute arsenic poisoning. In the present paper the effectiveness of glucose substitution was investigated in mice after acute experimental poisoning with As2O3. Four groups of ten mice each received As2O3, 12.9 mg/kg, s.c. After the injection the first group remained without further treatment, the second received saline every 2 h, the third 5% glucose, and the fourth 5% glucose +0.12 IE insulin/kg i.p. Groups 5 and 6, five mice each, received either saline or glucose only. Group 7, five mice, remained without any treatment. Immediately after death the livers were removed for the enzymatic determination of glucose and glycogen. Mice receiving As2O3 only died within 22 h. The mean survival time was 12.4 h. In mice receiving As2O3 and after that saline, glucose, or glucose + insulin, an increase in the survival time to 30.8, 40.7, and 43.6 h, respectively, was observed. All mice which died showed a significant decrease in the liver glucose and glycogen content, compared to control animals. In livers of survivors, the glucose and glycogen content was not different to the control groups. The data support the assumption that carbohydrate depletion is an important factor in arsenic toxicity, and its substitution should be considered in the treatment of arsenic poisoning.

  5. Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway of apoptosis in human leukemia (HL-60) cells

    PubMed Central

    2014-01-01

    Background Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), which accounts for approximately 10% of all acute myloid leukemia cases. It is a blood cancer that is formed by chromosomal mutation. Each year in the United States, APL affects about 1,500 patients of all age groups and causes approximately 1.2% of cancer deaths. Arsenic trioxide (ATO) has been used successfully for treatment of APL patients, and both induction and consolidated therapy have resulted in complete remission. Recently published studies from our laboratory have demonstrated that ATO pharmacology as an anti-leukemic drug is associated with cytotoxic and genotoxic effects in leukemia cells. Methods In the present study, we further investigated the detailed molecular mechanism of ATO-mediated intrinsic pathway of apoptosis; using HL-60 cells as a test model. Oxidative stress was assessed by spectrophotometric measurements of MDA and GSH levels while genotoxicity was determined by single cell gel electrophoresis (Comet assay). Apoptosis pathway was analyzed by Western blot analysis of Bax, Bcl2 and caspase 3 expression, as well as immunocytochemistry and confocal imaging of Bax and Cyt c translocation and mitochondrial membrane potential depolarization. Results ATO significantly (p < 0.05) induces oxidative stress, DNA damage, and caspase 3 activityin HL-60 cells in a dose-dependent manner. It also activated the intrinsic pathway of apoptosis by significantly modulating (p < 0.05) the expression and translocation of apoptotic molecules and decreasing the mitochondrial membrane potential in leukemia cells. Conclusion Taken together, our research demonstrated that ATO induces mitochondrial pathway of apoptosis in HL-60 cells. This apoptotic signaling is modulated via oxidative stress, DNA damage, and change in mitochondrial membrane potential, translocation and upregulation of apoptotic proteins leading programmed cell death. PMID:24887205

  6. Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

    SciTech Connect

    Chien, Chia-Wen; Yao, Ju-Hsien; Chang, Shih-Yu; Lee, Pei-Chih; Lee, Te-Chang

    2011-11-15

    The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivo in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: Black-Right-Pointing-Pointer ATO and SAHA are therapeutic agents with different action modes. Black-Right-Pointing-Pointer Combination of ATO and SAHA synergistically inhibits tumor cell growth. Black-Right-Pointing-Pointer SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. Black-Right-Pointing-Pointer ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.

  7. Comparison of Newly Diagnosed and Relapsed Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide: Insight into Mechanisms of Resistance

    PubMed Central

    Chendamarai, Ezhilarasi; Ganesan, Saravanan; Alex, Ansu Abu; Kamath, Vandana; Nair, Sukesh C.; Nellickal, Arun Jose; Janet, Nancy Beryl; Srivastava, Vivi; Lakshmi, Kavitha M.; Viswabandya, Auro; Abraham, Aby; Aiyaz, Mohammed; Mullapudi, Nandita; Mugasimangalam, Raja; Padua, Rose Ann; Chomienne, Christine; Chandy, Mammen; Srivastava, Alok; George, Biju; Balasubramanian, Poonkuzhali; Mathews, Vikram

    2015-01-01

    There is limited data on the clinical, cellular and molecular changes in relapsed acute promyeloytic leukemia (RAPL) in comparison with newly diagnosed cases (NAPL). We undertook a prospective study to compare NAPL and RAPL patients treated with arsenic trioxide (ATO) based regimens. 98 NAPL and 28 RAPL were enrolled in this study. RAPL patients had a significantly lower WBC count and higher platelet count at diagnosis. IC bleeds was significantly lower in RAPL cases (P=0.022). The ability of malignant promyelocytes to concentrate ATO intracellularly and their in-vitro IC50 to ATO was not significantly different between the two groups. Targeted NGS revealed PML B2 domain mutations in 4 (15.38%) of the RAPL subset and none were associated with secondary resistance to ATO. A microarray GEP revealed 1744 genes were 2 fold and above differentially expressed between the two groups. The most prominent differentially regulated pathways were cell adhesion (n=92), cell survival (n=50), immune regulation (n=74) and stem cell regulation (n=51). Consistent with the GEP data, immunophenotyping revealed significantly increased CD34 expression (P=0.001) in RAPL cases and there was in-vitro evidence of significant microenvironment mediated innate resistance (EM-DR) to ATO. Resistance and relapse following treatment with ATO is probably multi-factorial, mutations in PML B2 domain while seen only in RAPL may not be the major clinically relevant cause of subsequent relapses. In RAPL additional factors such as expansion of the leukemia initiating compartment along with EM-DR may contribute significantly to relapse following treatment with ATO based regimens. PMID:25822503

  8. Arsenic trioxide inhibits cancer stem-like cells via down-regulation of Gli1 in lung cancer.

    PubMed

    Chang, Ke-Jie; Yang, Meng-Hang; Zheng, Jin-Cheng; Li, Bing; Nie, Wei

    2016-01-01

    Cancer stem cells (CSCs) are responsible for the tumorigenesis and recurrence, so targeting CSCs is a potential effective method to cure cancers. Activated Hedgehog signaling pathway has been proved to be implicated in the maintenance of self-renewal of CSCs, and arsenic trioxide (As2O3) has been reported to inhibit Gli1, a key transcription factor of Hedgehog pathway. In this study, we evaluated whether As2O3 has inhibitory effects on cancer stem-like cells (CSLCs) in lung cancer and further explored the possible mechanism. CCK8 assay and colony formation assay were performed to demonstrate the ability of As2O3 to inhibit the growth of NCI-H460 and NCI-H446 cells, which represented non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), respectively. Tumor sphere formation assay was carried out to evaluate the effects of As2O3 on stem cell-like subpopulations. The expression of stem cell biomarkers CD133 and stem cell transcription factors such as Sox2 and Oct4 were detected. Moreover, the effects of As2O3 on expression of Gli1 and its target genes were observed. We found that As2O3 inhibited the cell proliferation and reduced the colony formation ability. Importantly, As2O3 decreased the formation of tumor spheres. The expression of stem cell biomarker CD133 and stem cell transcription factors such as Sox2 and Oct4 were markedly reduced by As2O3 treatment. Furthermore, As2O3 decreased the expression of Gli1, N-myc and GAS1. Our results suggested that As2O3 is a promising agent to inhibit CSLCs in lung cancer. In addition, the mechanism of CSLCs inhibition might involve Gli1 down-regulation. PMID:27158399

  9. A drug from poison: how the therapeutic effect of arsenic trioxide on acute promyelocytic leukemia was discovered.

    PubMed

    Rao, Yi; Li, Runhong; Zhang, Daqing

    2013-06-01

    It is surprising that, while arsenic trioxide (ATO) is now considered as "the single most active agent in patients with acute promyelocytic leukemia (APL)", the most important discoverer remains obscure and his original papers have not been cited by a single English paper. The discovery was made during the Cultural Revolution when most Chinese scientists and doctors struggled to survive. Beginning with recipes from a countryside practitioner that were vague in applicable diseases, Zhang TingDong and colleagues proposed in the 1970s that a single chemical in the recipe is most effective and that its target is APL. More than 20 years of work by Zhang and colleagues eliminated the confusions about whether and how ATO can be used effectively. Other researchers, first in China and then in the West, followed his lead. Retrospective analysis of data from his own group proved that APL was indeed the most sensitive target. Removal of a trace amount of mercury chloride from the recipe by another group in his hospital proved that only ATO was required. Publication of Western replication in 1998 made the therapy widely accepted, though neither Western, nor Chinese authors of English papers on ATO cited Zhang's papers in the 1970s. This article focuses on the early papers of Zhang, but also suggests it worth further work to validate Chinese reports of ATO treatment of other cancers, and infers that some findings published in Chinese journals are of considerable value to patients and that doctors from other countries can benefit from the clinical experience of Chinese doctors with the largest population of patients.

  10. Carnosic Acid-combined Arsenic Trioxide Antileukaemia Cells in the Establishment of NB4/SCID Mouse Model.

    PubMed

    Hao, Li; Ran, Wang; Xiang-Xin, Li; Lu-Qun, Wang; Xiao-Ning, Yu

    2016-09-01

    Despite great improvement in the treatment outcome of APL, treatment failure still sometimes occurs due to the toxicity of arsenic trioxide (ATO). Damage to the heart and liver often occurs even when the dose is lower than the therapeutic dose. Based on the results of cell experiments in vitro in this study, we investigated the synergistic activity of carnosic acid (CA) combined with ATO in the SCID mouse model of human promyelocytic leukaemia in vivo. A NB4/SCID mouse model was established in this study. The NB4/SCID mice were randomly divided into three treatment groups (CA alone, ATO alone and CA combined with ATO) and a control group based on factorial design. The evaluation indicators of the curative effect of the drugs included expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins by immunohistochemistry, flow cytometry and Western blot analysis. The survival time was compared between the four groups. The results indicated that verification of the NB4/SCID mouse model was confirmed by histopathological examination. Compared with mice treated by CA or ATO alone, the mice in the combination of CA and ATO group had a higher rate of apoptosis, which was linked with expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins. Also, the mice with the longest survival time were those treated with the combination of CA and ATO. In conclusion, the results of the present study indicated that CA and ATO in combination have strong synergistic antileukaemic effects on cell activity.

  11. A drug from poison: how the therapeutic effect of arsenic trioxide on acute promyelocytic leukemia was discovered.

    PubMed

    Rao, Yi; Li, Runhong; Zhang, Daqing

    2013-06-01

    It is surprising that, while arsenic trioxide (ATO) is now considered as "the single most active agent in patients with acute promyelocytic leukemia (APL)", the most important discoverer remains obscure and his original papers have not been cited by a single English paper. The discovery was made during the Cultural Revolution when most Chinese scientists and doctors struggled to survive. Beginning with recipes from a countryside practitioner that were vague in applicable diseases, Zhang TingDong and colleagues proposed in the 1970s that a single chemical in the recipe is most effective and that its target is APL. More than 20 years of work by Zhang and colleagues eliminated the confusions about whether and how ATO can be used effectively. Other researchers, first in China and then in the West, followed his lead. Retrospective analysis of data from his own group proved that APL was indeed the most sensitive target. Removal of a trace amount of mercury chloride from the recipe by another group in his hospital proved that only ATO was required. Publication of Western replication in 1998 made the therapy widely accepted, though neither Western, nor Chinese authors of English papers on ATO cited Zhang's papers in the 1970s. This article focuses on the early papers of Zhang, but also suggests it worth further work to validate Chinese reports of ATO treatment of other cancers, and infers that some findings published in Chinese journals are of considerable value to patients and that doctors from other countries can benefit from the clinical experience of Chinese doctors with the largest population of patients. PMID:23645104

  12. Relapsed APL patient with variant NPM-RARalpha fusion responded to arsenic trioxide-based therapy and achieved long-term survival.

    PubMed

    Chen, Yan; Gu, Ling; Zhou, Chenyan; Wu, Xueqiang; Gao, Ju; Li, Qiang; Zhu, Yiping; Jia, Cangsong; Ma, Zhigui

    2010-05-01

    The t(5;17)/NPM-RARalpha is the second variant chromosomal translocation in acute promyelocytic leukemia (APL) to be characterized and also the second most plentiful variant translocation. So far, there is a lack of information on the effectiveness of arsenic trioxide (ATO) in relapsed APL with variant RARalpha chimera including t(5;17)/NPM-RARalpha. We report here a long-term survived APL patient with variant NPM-RARalpha fusion who relapsed four times and each time responded well to ATO or ATO-based re-induction therapy. The patient had received a total of more than 3,500 mg of ATO, but showed no obvious arsenic-related toxicities. This case illustrates the long-term efficiency and safety of ATO-based therapy not only in newly diagnosed APL, but also in relapsed APL including those with variant translocations.

  13. Arsenic trioxide (AT) is a novel human neutrophil pro-apoptotic agent: effects of catalase on AT-induced apoptosis, degradation of cytoskeletal proteins and de novo protein synthesis.

    PubMed

    Binet, François; Cavalli, Hélène; Moisan, Eliane; Girard, Denis

    2006-02-01

    The anti-cancer drug arsenic trioxide (AT) induces apoptosis in a variety of transformed or proliferating cells. However, little is known regarding its ability to induce apoptosis in terminally differentiated cells, such as neutrophils. Because neutropenia has been reported in some cancer patients after AT treatment, we hypothesised that AT could induce neutrophil apoptosis, an issue that has never been investigated. Herein, we found that AT-induced neutrophil apoptosis and gelsolin degradation via caspases. AT did not increase neutrophil superoxide production and did not induce mitochondrial generation of reactive oxygen species. AT-induced apoptosis in PLB-985 and X-linked chronic granulomatous disease (CGD) cells (PLB-985 cells deficient in gp91(phox) mimicking CGD) at the same potency. Addition of catalase, an inhibitor of H2O2, reversed AT-induced apoptosis and degradation of the cytoskeletal proteins gelsolin, alpha-tubulin and lamin B1. Unexpectedly, AT-induced de novo protein synthesis, which was reversed by catalase. Cycloheximide partially reversed AT-induced apoptosis. We conclude that AT induces neutrophil apoptosis by a caspase-dependent mechanism and via de novo protein synthesis. H2O2 is of major importance in AT-induced neutrophil apoptosis but its production does not originate from nicotinamide adenine dinucleotide phosphate dehydrogenase activation and mitochondria. Cytoskeletal structures other than microtubules can now be considered as novel targets of AT.

  14. Folic acid or combination of folic acid and vitamin B(12) prevents short-term arsenic trioxide-induced systemic and mitochondrial dysfunction and DNA damage.

    PubMed

    Majumdar, Sangita; Mukherjee, Sandip; Maiti, Anasuya; Karmakar, Subhra; Das, Asankur Sekhar; Mukherjee, Maitrayee; Nanda, Arunabha; Mitra, Chandan

    2009-08-01

    The effect of folic acid and folic acid + vitamin B(12) supplementation upon short-term arsenic-induced systemic and pancreatic islet cell mitochondria oxidative stress was investigated in male rats. Arsenic trioxide was administered orally at a dose of 3 mg kg body weight(-1) day(-1) for 30 days, and folic acid and vitamin B(12) were administered at a dose of 36 and 0.63 microg kg body weight(-1) day(-1), respectively, for 30 days. Compared to control, arsenic-treated group showed a significant increase in the levels of systemic oxidative markers, malondialdehyde (MDA), nitric oxide (NO), and hydroxyl radical (OH(-)) formation, which were found decreased significantly after supplementation either with folic acid or a combination of folic acid + vitamin B(12). Similar supplementations were found effective against arsenic-induced oxidative marker changes (MDA, NO, and OH(-)) in pancreatic islet cell mitochondria. Also, low activities of antioxidant defense enzymes such as superoxide dismutase and catalase, and level of antioxidant glutathione, all could regain significantly on supplementations both against systemic and islet cell mitochondria oxidative stress. Results of agarose-gel electrophoresis of DNA from lymphocytes and islet cells of arsenic-exposed rats showed DNA smearing, which could be reduced with simultaneous administration either with folic acid or a combination of folic acid + vitamin B(12). Significantly, similar supplementations were found effective in increasing the urinary clearance of arsenic. Together, these results indicate that folic acid and vitamin B(12) may be effective to reduce the arsenic-induced damage at molecular target level.

  15. Requirement of PML SUMO Interacting Motif for RNF4- or Arsenic Trioxide-Induced Degradation of Nuclear PML Isoforms

    PubMed Central

    El Asmi, Faten; Dianoux, Laurent; Aubry, Muriel; Chelbi-Alix, Mounira K.

    2012-01-01

    PML, the organizer of nuclear bodies (NBs), is expressed in several isoforms designated PMLI to VII which differ in their C-terminal region due to alternative splicing of a single gene. This variability is important for the function of the different PML isoforms. PML NB formation requires the covalent linkage of SUMO to PML. Arsenic trioxide (As2O3) enhances PML SUMOylation leading to an increase in PML NB size and promotes its interaction with RNF4, a poly-SUMO-dependent ubiquitin E3 ligase responsible for proteasome-mediated PML degradation. Furthermore, the presence of a bona fide SUMO Interacting Motif (SIM) within the C-terminal region of PML seems to be required for recruitment of other SUMOylated proteins within PML NBs. This motif is present in all PML isoforms, except in the nuclear PMLVI and in the cytoplasmic PMLVII. Using a bioluminescence resonance energy transfer (BRET) assay in living cells, we found that As2O3 enhanced the SUMOylation and interaction with RNF4 of nuclear PML isoforms (I to VI). In addition, among the nuclear PML isoforms, only the one lacking the SIM sequence, PMLVI, was resistant to As2O3-induced PML degradation. Similarly, mutation of the SIM in PMLIII abrogated its sensitivity to As2O3-induced degradation. PMLVI and PMLIII-SIM mutant still interacted with RNF4. However, their resistance to the degradation process was due to their inability to be polyubiquitinated and to recruit efficiently the 20S core and the β regulatory subunit of the 11S complex of the proteasome in PML NBs. Such resistance of PMLVI to As2O3-induced degradation was alleviated by overexpression of RNF4. Our results demonstrate that the SIM of PML is dispensable for PML SUMOylation and interaction with RNF4 but is required for efficient PML ubiquitination, recruitment of proteasome components within NBs and proteasome-dependent degradation of PML in response to As2O3. PMID:23028697

  16. Treatment of an acute promyelocytic leukemia relapse using arsenic trioxide and all-trans-retinoic in a 6-year-old child.

    PubMed

    Rock, Nathalie; Mattiello, V; Judas, C; Huezo-Diaz, P; Bourquin, J P; Gumy-Pause, F; Ansari, M

    2014-03-01

    In adult therapy, arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) are recognized as active treatment of relapsed acute promyelocytic leukemia (APL). The efficacy of this combination in pediatric APL has not yet been well established. We report the case of a 6-year-old girl with relapsed APL, with a PML-RARα mutation, treated with a combination of ATO and ATRA. Over a period of 5 months, she received in total, 75 doses of intravenous ATO and 40 doses of oral ATRA. Currently, 22 months after relapse, she is still in complete remission. Here, we describe treatment of a relapsed APL in a child with limited treatment of ATO and ATRA and review the literature. PMID:24498972

  17. Arsenic trioxide suppresses liver X receptor β and enhances cholesteryl ester transfer protein expression without affecting the liver X receptor α in HepG2 cells.

    PubMed

    Cheng, Tain-Junn; Lin, Shu-Wen; Chen, Chih-Wei; Guo, How-Ran; Wang, Ying-Jang

    2016-10-25

    Chronic arsenic exposure is associated with cerebrovascular disease and the formation of atherosclerotic lesions. Our previous study demonstrated that arsenic trioxide (ATO) exposure was associated with atherosclerotic lesion formation through alterations in lipid metabolism in the reverse cholesterol transport process. In mouse livers, the expression of the liver X receptor β (LXR-β) and the cholesteryl ester transfer protein (CETP) was suppressed without any changes to the lipid profile. The aim of this study was to elucidate whether ATO contributes to atherosclerotic lesions by suppressing LXR-β and CETP levels in hepatocytes. HepG2 cells, human hepatocytes, were exposed to different ATO concentrations in vitro. Cell viability was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. The liver X receptor α (LXR-α), LXR-β, sterol regulatory element-binding protein-1c (SREBP-1c) and CETP protein levels were measured by Western blotting, and their mRNA levels were measured by real-time PCR. Cholesterol efflux was analyzed by flow cytometry. The results showed ATO inhibited LXR-β mRNA and protein levels with a subsequent decrease in SREBP-1c protein levels and reduced cholesterol efflux from HepG2 cells into the extracellular space without influencing LXR-α mRNA and protein levels. CETP protein levels of HepG2 cells were significantly elevated under arsenic exposure. Transfection of LXR-β shRNA did not change CETP protein levels, implying that there is no cross-talk between LXR-β and CETP. In conclusion, arsenic not only inhibits LXR-β and SREBP-1c mRNA and protein levels but also independently increases CETP protein levels in HepG2 cells. PMID:27622732

  18. Granulocyte colony-stimulating factor potentiates differentiation induction by all-trans retinoic acid and arsenic trioxide and enhances arsenic uptake in the acute promyelocytic leukemia cell line HT93A.

    PubMed

    Iriyama, Noriyoshi; Yuan, Bo; Hatta, Yoshihiro; Horikoshi, Akira; Yoshino, Yuta; Toyoda, Hiroo; Aizawa, Shin; Takeuchi, Jin

    2012-11-01

    The effects of arsenic trioxide (ATO), all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF), alone or in combination, were investigated by focusing on differentiation, growth inhibition and arsenic uptake in the acute promyelocytic leukemia (APL) cell line HT93A. ATO induced differentiation at low concentrations (0.125 µM) and apoptosis at high concentrations (1-2 µM). Furthermore, ATRA induced greater differentiation than ATO. No synergistic effect of ATRA and ATO was found on differentiation. G-CSF promoted differentiation-inducing activities of both ATO and ATRA. The combination of ATRA and G-CSF showed maximum differentiation and ATO addition was not beneficial. Addition of 1 µM ATRA and/or 50 ng/ml G-CSF to ATO did not affect apoptosis compared to ATO treatment alone. ATRA induced expression of aquaporin-9 (AQP9), a transmembrane transporter recognized as a major pathway of arsenic uptake, in a time- and dose-dependent manner. However, treatment with 1 µM ATRA decreased arsenic uptake by 43.7% compared to control subject. Although G-CSF addition did not enhance AQP9 expression in the cells, the reduced arsenic uptake was recovered to the same level as that in controls. ATRA decreased cell viability and addition of 50 ng/ml G-CSF to ATRA significantly increased the number of viable cells compared with that in ATRA alone treated cells. G-CSF not only promotes differentiation-inducing activities of both ATRA and ATO, but also makes APL cells vulnerable to increased arsenic uptake. These observations provide new insights into combination therapy using these three agents for the treatment of APL.

  19. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia.

    PubMed

    Hu, Jiong; Liu, Yuan-Fang; Wu, Chuan-Feng; Xu, Fang; Shen, Zhi-Xiang; Zhu, Yong-Mei; Li, Jun-Min; Tang, Wei; Zhao, Wei-Li; Wu, Wen; Sun, Hui-Ping; Chen, Qiu-Sheng; Chen, Bing; Zhou, Guang-Biao; Zelent, Arthur; Waxman, Samuel; Wang, Zhen-Yi; Chen, Sai-Juan; Chen, Zhu

    2009-03-01

    All-trans retinoic acid (ATRA)/arsenic trioxide (ATO) combination-based therapy has benefitted newly diagnosed acute promyelocytic leukemia (APL) in short-term studies, but the long-term efficacy and safety remained unclear. From April 2001, we have followed 85 patients administrated ATRA/ATO with a median follow-up of 70 months. Eighty patients (94.1%) entered complete remission (CR). Kaplan-Meier estimates of the 5-year event-free survival (EFS) and overall survival (OS) for all patients were 89.2% +/- 3.4% and 91.7% +/- 3.0%, respectively, and the 5-year relapse-free survival (RFS) and OS for patients who achieved CR (n = 80) were 94.8% +/- 2.5% and 97.4% +/- 1.8%, respectively. Upon ATRA/ATO, prognosis was not influenced by initial white blood cell count, distinct PML-RARalpha types, or FLT3 mutations. The toxicity profile was mild and reversible. No secondary carcinoma was observed, and 24 months after the last dose of ATRA/ATO, patients had urine arsenic concentrations well below the safety limit. These results demonstrate the high efficacy and minimal toxicity of ATRA/ATO treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for de novo APL.

  20. 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

  1. Arsenic Trioxide Reduces Global Histone H4 Acetylation at Lysine 16 through Direct Binding to Histone Acetyltransferase hMOF in Human Cells

    PubMed Central

    Liu, Da; Wu, Donglu; Zhao, Linhong; Yang, Yang; Ding, Jian; Dong, Liguo; Hu, Lianghai; Wang, Fei; Zhao, Xiaoming; Cai, Yong; Jin, Jingji

    2015-01-01

    Histone post-translational modification heritably regulates gene expression involved in most cellular biological processes. Experimental studies suggest that alteration of histone modifications affects gene expression by changing chromatin structure, causing various cellular responses to environmental influences. Arsenic (As), a naturally occurring element and environmental pollutant, is an established human carcinogen. Recently, increasing evidence suggests that As-mediated epigenetic mechanisms may be involved in its toxicity and carcinogenicity, but how this occurs is still unclear. Here we present evidence that suggests As-induced global histone H4K16 acetylation (H4K16ac) partly due to the direct physical interaction between As and histone acetyltransferase (HAT) hMOF (human male absent on first) protein, leading to the loss of hMOF HAT activity. Our data show that decreased global H4K16ac and increased deacetyltransferase HDAC4 expression occurred in arsenic trioxide (As2O3)-exposed HeLa or HEK293T cells. However, depletion of HDAC4 did not affect global H4K16ac, and it could not raise H4K16ac in cells exposed to As2O3, suggesting that HDAC4 might not directly be involved in histone H4K16 de-acetylation. Using As-immobilized agarose, we confirmed that As binds directly to hMOF, and that this interaction was competitively inhibited by free As2O3. Also, the direct interaction of As and C2CH zinc finger peptide was verified by MAIDI-TOF mass and UV absorption. In an in vitro HAT assay, As2O3 directly inhibited hMOF activity. hMOF over-expression not only increased resistance to As and caused less toxicity, but also effectively reversed reduced H4K16ac caused by As exposure. These data suggest a theoretical basis for elucidating the mechanism of As toxicity. PMID:26473953

  2. Aquaporin 9, a promising predictor for the cytocidal effects of arsenic trioxide in acute promyelocytic leukemia cell lines and primary blasts.

    PubMed

    Iriyama, Noriyoshi; Yuan, Bo; Yoshino, Yuta; Hatta, Yoshihiro; Horikoshi, Akira; Aizawa, Shin; Takeuchi, Jin; Toyoda, Hiroo

    2013-06-01

    A close correlation between the cytocidal effects of arsenic trioxide (ATO) and aquaporin-9 (AQP9) expression levels has been proposed, yet detailed studies are still needed to confirm this association. Thus, in the present study, the correlation between the expression levels of AQP9 and sensitivity to ATO was investigated using two acute promyelocytic leukemia (APL) cell lines, NB4 and HT93A, as well as primary APL cells from newly diagnosed and relapsed APL patients. A substantially higher sensitivity to ATO-mediated induction of apoptosis was observed in the NB4 cells when compared to that in the HT93A cells. In addition, markedly higher expression levels of AQP9, as assessed using flow cytometry, along with more intracellular arsenic accumulation, were observed in the NB4 cells. More importantly, similar to APL cell lines, the trend of expression levels of AQP9 correlated closely with the differential sensitivity to ATO-mediated induction of apoptosis in primary APL cells. In contrast, no correlation was observed between ATO sensitivity associated with AQP9 expression levels and the expression profiles of cell surface markers as well as chromosomal alterations. These results provide direct evidence that the expression levels of AQP9, rather than other biomarkers such as cell surface markers and chromosomal alterations, correlate closely with the sensitivity to ATO in both APL cell lines and primary blasts. These findings suggest that the AQP9 expression status of APL patients is a predictive marker for the successful outcome of ATO treatment, since AQP9 plays a pivotal role in various arsenite-mediated biological effects on normal and cancer cells. Moreover, flow cytometry may be a new convenient and valuable tool for analyzing the AQP9 status of APL patients compared to current methods such as western blotting.

  3. Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

    SciTech Connect

    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na; Choe, Tae-Boo; Hong, Seok-Il; Yi, Jae-Youn; Hwang, Sang-Gu; Lee, Hyun-Gyu; Lee, Yun-Han; Park, In-Chul

    2014-07-11

    Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

  4. The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome.

    PubMed

    Burnett, A K; Hills, R K; Hunter, A; Milligan, D; Kell, J; Wheatley, K; Yin, J; McMullin, M-F; Cahalin, P; Craig, J; Bowen, D; Russell, N

    2011-07-01

    Most patients with acute myeloid leukaemia (AML) are older, with many unsuitable for conventional chemotherapy. Low-dose Ara-C (LDAC) is superior to best supportive care but is still inadequate. The combination of arsenic trioxide (ATO) and LDAC showed promise in an unrandomised study. We report a randomised trial of LDAC versus LDAC+ATO. Patients with AML according to WHO criteria or myelodysplastic syndrome with >10% blasts, considered as unfit for conventional chemotherapy, were randomised between subcutaneous Ara-C (20 mg b.d. for 10 days) and the same LDAC schedule with ATO (0.25 mg/kg) on days 1-5, 9 and 11, for at least four courses every 4 to 6 weeks. Overall 166 patients were entered; the trial was terminated on the advice of the DMC, as the projected benefit was not observed. Overall 14% of patients achieved complete remission (CR) and 7% CRi. Median survival was 5.5 months and 19 months for responders (CR: not reached; CRi: 14 months; non-responders: 4 months). There were no differences in response or survival between the arms. Grade 3/4 cardiac and liver toxicity, and supportive care requirements were greater in the ATO arm. This randomised comparison demonstrates that adding ATO to LDAC provides no benefit for older patients with AML.

  5. The influence of joint application of arsenic trioxide and daunorubicin on primary acute promyelocytic leukaemia cells and apoptosis and blood coagulation of cell strain.

    PubMed

    Zhang, Xiaojuan; Qin, Na; Chen, Xinghua; Guo, Shuxia

    2015-05-01

    This test cultivated three groups of acute promyelocytic leukemia (APL) and NB4 cells in liquid in vitro, processed them with arsenic trioxide (ATO), daunorubicin (DNR), ATO+DNR respectively, and then set up blank control group. Apoptosis of cells in each group was observed using flow cytometry, procoagulant activity of APL and NB4 cells in each group was detected with recalcification time, and expressions of tissue factor (TF), thrombomodulin and annexin II of NB4 cells in each group were measured using ELISA method. The results showed that the apoptosis rate increased 4-8 times compared with blank control group after processing APL and NB4 cells with ATO and DNR; procoagulant activity decreased obviously; and expression of TF and annexin II of NB4 cells reduced significantly (P<0.05). We concluded that combination of ATO and DNR could promote APL and NB4 cell apoptosis effectively without aggravating blood coagulation disorders, which might improve coagulation function of APL by inhibiting coagulation and hyperfibrinolysis through reducing expression of TF and annexin II. This drug combination may be a safe and effective method in the treatment of APL of primary high white blood cells type.

  6. Arsenic trioxide and interferon-alpha synergize to induce cell cycle arrest and apoptosis in human T-cell lymphotropic virus type I-transformed cells.

    PubMed

    Bazarbachi, A; El-Sabban, M E; Nasr, R; Quignon, F; Awaraji, C; Kersual, J; Dianoux, L; Zermati, Y; Haidar, J H; Hermine, O; de Thé, H

    1999-01-01

    Human T-cell lymphotropic virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATL). ATL is an aggressive proliferation of mature activated T cells associated with a poor prognosis. The combination of the antiviral agents, zidovudine (AZT) and interferon (IFN), is a potent treatment of ATL. Recently, arsenic trioxide (As) was shown to be an effective treatment of acute promyelocytic leukemia (APL). We have tested the effects of the combination of As and IFN on cell proliferation, cell cycle phases distribution, and apoptosis in ATL-derived or control T-cell lines. A high synergistic effect between IFN and As was observed in ATL-derived cell lines in comparison to the control cell lines, with a dramatic inhibition of cell proliferation, G1 arrest, and induction of apoptosis. Similar results were obtained with fresh leukemia cells derived from an ATL patient. Although the mechanisms involved are unclear, these results could provide a rational basis for combined As and IFN treatments in ATL. PMID:9864171

  7. Inactivation of Akt by arsenic trioxide induces cell death via mitochondrial-mediated apoptotic signaling in SGC-7901 human gastric cancer cells.

    PubMed

    Gao, Yan-Hui; Zhang, Hao-Peng; Yang, Shu-Meng; Yang, Yue; Ma, Yu-Yan; Zhang, Xin-Yu; Yang, Yan-Mei

    2014-04-01

    Arsenic trioxide (As2O3) has been recognized as a potential chemotherapeutic agent, yet the details concerning its mechanism of action in solid cancers remain undetermined. The present study assessed the role of Akt in the cell death induced by As2O3. The MTT assay showed that As2O3 suppressed the proliferation of SGC-7901 cells in a dose- and time-dependent manner. Characteristic apoptotic changes were observed in the As2O3‑treated cells by Hoechst 33342 staining, and FACS analysis showed that As2O3 caused dose-dependent apoptotic cell death. As2O3 activated caspase-3 and -9, and PARP cleavage in a dose-dependent manner. Compromised mitochondrial membrane potential and an increased protein level of Bax indicated involvement of mitochondia. As2O3 decreased the levels of p-Akt (Ser473), p-Akt (Thr308) and p-GSK-3β (Ser9), suggesting that As2O3 inactivated Akt kinase. In addition, LY294002 (a PI3 kinase inhibitor) augmented the apoptosis induced by As2O3. These results demonstrated that inhibition of PI3K/Akt signaling was involved in As2O3-induced apoptosis of gastric cancer SGC-7901 cells. PMID:24482137

  8. Utilization of arsenic trioxide as a treatment of cisplatin-resistant non-small cell lung cancer PC-9/CDDP and PC-14/CDDP cells

    PubMed Central

    SUZUKI, TOSHIHIRO; ISHIBASHI, KENICHI; YUMOTO, ATSUSHI; NISHIO, KAZUTO; OGASAWARA, YUKI

    2015-01-01

    Cisplatin is a commonly used drug in combination chemotherapy. However, various malignant tumors frequently acquire resistance to cisplatin. Arsenic trioxide (ATO) has been approved as a chemotherapeutic drug for the treatment of acute promyelocytic leukemia, and the combination of ATO and cisplatin has been revealed to demonstrate synergistic effects in ovarian and small cell lung cancer cells. Thus, it was hypothesized that ATO may also be active against cisplatin-resistant non-small cell lung cancer (NSCLC) PC-9/CDDP and PC-14/CDDP cells. The present study also evaluated the effects of ATO on the cisplatin-sensitive NSCLC PC-9 and PC-14 cell lines. Notably, ATO demonstrated a markedly decreased IC50 in the cisplatin-resistant PC-9/CDDP and PC-14/CDDP cells compared with the IC50 in the cisplatin-sensitive parental PC-9 and PC-14 cells. Additionally, it was found that arsenite accumulation in the PC-9 cell line was affected through the downregulation of GS-X pump systems. Although it is likely that cisplatin resistance in PC-9 cells does not depend on the GS-X pump systems, ATO was effective against cisplatin-resistant NSCLC PC-9/CDDP and PC-14/CDDP cells in combination chemotherapy. PMID:26622574

  9. Arsenic trioxide and radiation enhance apoptotic effects in HL-60 cells through increased ROS generation and regulation of JNK and p38 MAPK signaling pathways.

    PubMed

    Ho, Sheng-Yow; Wu, Wei-Jr; Chiu, Hui-Wen; Chen, Yi-An; Ho, Yuan-Soon; Guo, How-Ran; Wang, Ying-Jan

    2011-09-01

    The induction of apoptotic cell death is a significant mechanism of tumor cells under the influence of radio-/chemotherapy, and resistance to these treatments has been linked to some cancer cell lines with a low propensity for apoptosis. The present study aimed to investigate the enhanced effects and mechanisms in apoptosis and the cycle distribution of HL-60 cells, a human leukemia cell line lacking a functional p53 protein, after combination treatment with arsenic trioxide (ATO) and irradiation (IR). Our results indicated that combined treatment led to increased cytotoxicity and apoptotic cell death in HL-60 cells, which was correlated with the activation of cdc-2 and increased expression of cyclin B, the induction of intracellular reactive oxygen species (ROS) generation, the loss of mitochondria membrane potential, and the activation of caspase-3. The combined treatment of HL-60 cells pre-treated with Z-VAD or NAC resulted in a significant reduction in apoptotic cells. In addition, activation of JNK and p38 MAPK may be involved in combined treatment-mediated apoptosis. The data suggest that a combination of IR and ATO could be a potential therapeutic strategy against p53-deficient leukemia cells.

  10. Arsenic Trioxide Amplifies Cisplatin Toxicity in Human Tubular Cells Transformed by HPV-16 E6/E7 for Further Therapeutic Directions in Renal Cell Carcinoma

    PubMed Central

    Dogra, Samriti; Bandi, Sriram; Viswanathan, Preeti; Gupta, Sanjeev

    2014-01-01

    Human papillomavirus (HPV) DNA integrations may affect therapeutic responses in cancers through ATM network-related DNA damage response (DDR). We studied whether cisplatin-induced DDR was altered in human HK-2 renal tubular cells immortalized by HPV16 E6/E7 genes. Cytotoxicity assays utilized thiazolyl blue dye and DDR was identified by gene expression differences, double-strand DNA breaks, ATM promoter activity, and analysis of cell cycling and side population cells. After cisplatin, HK-2 cells showed greater ATM promoter activity indicating activation of this network, but DDR was muted, since little γH2AX was expressed, DNA strand breaks were absent and cells continued cycling. When HK-2 cells were treated with the MDM2 antagonist inducing p53, nutlin-3, or p53 transcriptional activator, tenovin-1, cell growth decreased but cisplatin toxicity was unaffected. By contrast, arsenic trioxide, which by inhibiting wild-type p53-induced phosphatase-1 that serves responses downstream of p53, and by depolymerizing tubulin, synergistically enhanced cisplatin cytotoxicity including loss of SP cells. Our findings demonstrated that HPV16 E6/E7 altered DDR through p53-mediated cell growth controls, which may be overcome by targeting of WIP1 and other processes, and thus should be relevant for treating renal cell carcinoma. PMID:25444910

  11. Phloretin ameliorates arsenic trioxide induced mitochondrial dysfunction in H9c2 cardiomyoblasts mediated via alterations in membrane permeability and ETC complexes.

    PubMed

    Vineetha, Vadavanath Prabhakaran; Soumya, Rema Sreenivasan; Raghu, Kozhiparambil Gopalan

    2015-05-01

    Arsenic trioxide (ATO), though a very effective drug for the treatment of acute promyelocytic leukemia, leads to cardiotoxicity. As mitochondria are the center of attention of cardiac cell׳s general metabolic status, it is primarily important to see the interaction of ATO with mitochondria. Studies related exclusively to the alterations in mitochondria and its associated functions caused by ATO are very limited. The present investigation aims to explore the effect of ATO on various components of electron transport chain, oxygen consumption, ATP production, mitochondrial superoxide generation, transmembrane potential, permeability pore opening, calcium homeostasis and apoptosis. Attempts were also made to see the efficacy of phloretin, a potent antioxidant flavonoid found majorly in apple peel on cardiotoxicity. The H9c2 cells exposed to ATO (5µM) exhibited increased oxidative stress with reduced innate antioxidant status, mitochondrial dysfunctions and apoptosis. It increased the intracellular calcium content, caused alterations in the activity of transcription factor Nrf2, xanthine oxidase, aconitase and caspase 3 compared to the control group. Phloretin at 2.5 and 5µM concentrations were able to protect the cells from ATO toxicity via protecting mitochondria through its antioxidant potential. The present investigation based on mitochondria reveals the probability of cardioprotective potential of phloretin for the cancer patients on ATO chemotherapy. PMID:25746422

  12. The mechanism of synergistic effects of arsenic trioxide and rapamycin in acute myeloid leukemia cell lines lacking typical t(15;17) translocation.

    PubMed

    Dembitz, Vilma; Lalic, Hrvoje; Ostojic, Alen; Vrhovac, Radovan; Banfic, Hrvoje; Visnjic, Dora

    2015-07-01

    Arsenic trioxide (ATO) has potent clinical activity in the treatment of patients with acute promyelocytic leukemia (APL), but is much less efficacious in acute myeloid leukemia (AML) lacking t(15;17) translocation. Recent studies have indicated that the addition of mammalian target of rapamycin (mTOR) inhibitors may increase the sensitivity of malignant cells to ATO. The aim of the present study was to test for possible synergistic effects of ATO and rapamycin at therapeutically achievable doses in non-APL AML cells. In HL-60 and U937 cell lines, the inhibitory effects of low concentrations of ATO and rapamycin were synergistic and more pronounced in U937 cells. The combination of drugs increased apoptosis in HL-60 cells and increased the percentage of cells in G(0)/G(1) phase in both cell lines. In U937 cells, rapamycin alone increased the activity of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and the addition of ATO decreased the level of phosphorylated ERK, Ser473 phosphorylated Akt and anti-apoptotic Mcl-1 protein. Primary AML cells show high sensitivity to growth-inhibitory effects of rapamycin alone or in combination with ATO. The results of the present study reveal the mechanism of the synergistic effects of two drugs at therapeutically achievable doses in non-APL AML cells. PMID:25758096

  13. Arsenic trioxide induces de novo protein synthesis of annexin-1 in neutrophils: association with a heat shock-like response and not apoptosis.

    PubMed

    Binet, François; Chiasson, Sonia; Girard, Denis

    2008-02-01

    We recently demonstrated that arsenic trioxide (ATO) induced apoptosis in human neutrophils and increased de novo protein synthesis. Here, we identified one of these newly synthesized proteins as annexin-1 (AnxA1), a protein recently found to be proapoptotic in neutrophils when added exogenously. AnxA1 was detected at the cell membrane of ATO-induced neutrophils as well as in the supernatants. Using neutrophils harvested from AnxA1 knockout mice, we found that the proapoptotic activity of ATO was similar in neutrophils, regardless of AnxA1 levels. A second protein was identified as heat shock protein (Hsp) 89alpha. Because ATO is known to induce a HS-like response in a variety of cells, we investigated its ability to induce gene expression of Hsp in neutrophils and found that ATO increases HSP90AA1, HSPA1 and HSPB1 mRNA in these cells. We conclude that ATO-induced neutrophil apoptosis by an AnxA1-independent mechanism. Our data provide the first evidence that ATO induces a stress response in human neutrophils and that de novo synthesis of AnxA1 is related to this event rather than to the proapoptotic activity of ATO.

  14. Protection against arsenic trioxide-induced autophagic cell death in U118 human glioma cells by use of lipoic acid.

    PubMed

    Cheng, Tain-Junn; Wang, Ying-Jan; Kao, Wei-Wan; Chen, Rong-Jane; Ho, Yuan-Soon

    2007-06-01

    Arsenic is an environmental toxicant found naturally in ground water. Epidemiological studies have suggested a correlation between chronic arsenic exposure and potential brain tissue damage in clinical case and animal experiments. Lipoic acid (LA) is a thiol-compound naturally occurring in plants and animals, which is thought to be a strong antioxidant and possess neuroprotective effects. The objective of this study was to determine if the AS(2)O(3)-induced glial cell toxicity could be prevented by LA. The human malignant glioma cell (U118) was selected as a research model. By using acridine orange staining and flow cytometry analysis, we found that autophagic, but not apoptotic, cell death was significantly induced by AS(2)O(3) in U118 cells, and that AS(2)O(3)-mediated autophagic cell death was nearly completely attenuated by LA. Down-regulation of p53 and Bax proteins and the up-regulation of Bcl-2 and HSP-70 proteins were observed by western blot in AS(2)O(3)-mediated autophagic cell death. Our results implied that LA completely inhibited U118 cells autophagic cell death induced by AS(2)O(3). We suggested that LA may emerge as a useful protective agent against arsenic-induced glial cell toxicity and reversing arsenic-induced damage in human brain.

  15. Arsenic trioxide (As{sub 2}O{sub 3}) induced calcium signals and cytotoxicity in two human cell lines: SY-5Y neuroblastoma and 293 embryonic kidney (HEK)

    SciTech Connect

    Florea, Ana-Maria; Splettstoesser, Frank; Buesselberg, Dietrich . E-mail: Dietrich.Buesselberg@uni-due.de

    2007-05-01

    Arsenic trioxide (As{sub 2}O{sub 3}) has anticancer properties; however, its use also leads to neuro-, hepato- or nephro-toxicity, and therefore, it is important to understand the mechanism of As{sub 2}O{sub 3} toxicity. We studied As{sub 2}O{sub 3} influence on intracellular calcium ([Ca{sup 2+}]{sub i}) homeostasis of human neuroblastoma SY-5Y and embryonic kidney cells (HEK 293).We also relate the As{sub 2}O{sub 3} induced [Ca{sup 2+}]{sub i} modifications with cytotoxicity. We used Ca{sup 2+} sensitive dyes (fluo-4 and rhod-2) combined with laser scanning microscopy or fluorescence activated cell sorting to measure Ca{sup 2+} changes during the application of As{sub 2}O{sub 3} and we approach evaluation of cytotoxicity. As{sub 2}O{sub 3} (1 {mu}M) increased [Ca{sup 2+}]{sub i} in SY-5Y and HEK 293 cells. Three forms of [Ca{sup 2+}]{sub i}-elevations were found: (1) steady-state increases (2) transient [Ca{sup 2+}]{sub i}-elevations and (3) Ca{sup 2+}-spikes. [Ca{sup 2+}]{sub i} modifications were independent from extracellular Ca{sup 2+} but dependent on internal calcium stores. The effect was not reversible. Inositol triphosphate (IP{sub 3}) and ryanodine (Ry) receptors are involved in regulation of signals induced by As{sub 2}O{sub 3}. 2-APB and dantrolene significantly reduced the [Ca{sup 2+}]{sub i}-rise (p < 0.001, t-test) but did not completely abolish [Ca{sup 2+}]{sub i}-elevation or spiking. This indicates that other Ca{sup 2+} regulating mechanisms are involved. In cytotoxicity tests As{sub 2}O{sub 3} significantly reduced cell viability in both cell types. Staining with Hoechst 33342 showed occurrence of apoptosis and DNA damage. Our data suggest that [Ca{sup 2+}]{sub i} is an important messenger in As{sub 2}O{sub 3} induced cell death.

  16. Antimony trioxide

    Integrated Risk Information System (IRIS)

    Antimony trioxide ; CASRN 1309 - 64 - 4 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 Noncarcinogeni

  17. Comparative study of the toxic effects of gallium arsenide, indium arsenide and arsenic trioxide following intratracheal instillations to the lung of Syrian golden hamsters.

    PubMed

    Tanaka, A; Hirata, M; Omura, M; Zhao, M; Makita, Y; Yamazaki, K; Inoue, N; Gotoh, K

    2000-01-01

    Toxic effects of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were studied in male Syrian golden hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) particles were instilled intratracheally twice a week a total of 16 times, while InAs (7.7 mg/kg) was instilled a total of 14 times. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During the instillation period, the cumulative body weight gain of the InAs-, but not the GaAs- or As2O3-treated hamsters was suppressed significantly, when compared with the control group. Slight to severe inflammatory responses were observed in the lung for all treatment groups. The most severe inflammatory change, characterized by an accumulation of neutrophils and macrophages, exudation, thickness of the pleura and fibrotic proliferation was found in the InAs-treated hamsters. Extensive alveolar or bronchiolar cell hyperplasia with or without keratinizing squamous cell metaplasia was observed in almost all the InAs-treated hamsters. Furthermore, squamous cell metaplasia or squamous cell hyperplasia developed in some of the InAs-treated hamsters, but not in the GaAs- or As2O3-treated hamsters. Slight to mild lesions were found in the convoluted tubules of the kidney in both the GaAs and InAs groups. From the present study, the toxic potency of these particles was provisionally estimated to be in the following order: InAs > GaAs > As2O3, at the dosage level used in this study. Furthermore, there was evidence that InAs particles could induce pulmonary, renal or systemic toxicity, and as such, InAs particles may produce pulmonary precancerous change when instilled intratracheally into hamsters.

  18. Arsenic Trioxide Overcomes Rapamycin-Induced Feedback Activation of AKT and ERK Signaling to Enhance the Anti-Tumor Effects in Breast Cancer

    PubMed Central

    Guilbert, Cynthia; Annis, Matthew G.; Dong, Zhifeng; Siegel, Peter M.; Miller, Wilson H.; Mann, Koren K.

    2013-01-01

    Inhibitors of the mammalian target of rapamycin (mTORi) have clinical activity; however, the benefits of mTOR inhibition by rapamycin and rapamycin-derivatives (rapalogs) may be limited by a feedback mechanism that results in AKT activation. Increased AKT activity resulting from mTOR inhibition can be a result of increased signaling via the mTOR complex, TORC2. Previously, we published that arsenic trioxide (ATO) inhibits AKT activity and in some cases, decreases AKT protein expression. Therefore, we propose that combining ATO and rapamycin may circumvent the AKT feedback loop and increase the anti-tumor effects. Using a panel of breast cancer cell lines, we find that ATO, at clinically-achievable doses, can enhance the inhibitory activity of the mTORi temsirolimus. In all cell lines, temsirolimus treatment resulted in AKT activation, which was decreased by concomitant ATO treatment only in those cell lines where ATO enhanced growth inhibition. Treatment with rapalog also results in activated ERK signaling, which is decreased with ATO co-treatment in all cell lines tested. We next tested the toxicity and efficacy of rapamycin plus ATO combination therapy in a MDA-MB-468 breast cancer xenograft model. The drug combination was well-tolerated, and rapamycin did not increase ATO-induced liver enzyme levels. In addition, combination of these drugs was significantly more effective at inhibiting tumor growth compared to individual drug treatments, which corresponded with diminished phospho-Akt and phospho-ERK levels when compared with rapamycin-treated tumors. Therefore, we propose that combining ATO and mTORi may overcome the feedback loop by decreasing activation of the MAPK and AKT signaling pathways. PMID:24392034

  19. ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction underlie apoptosis induced by resveratrol and arsenic trioxide in A549 cells.

    PubMed

    Gu, Shiyan; Chen, Chengzhi; Jiang, Xuejun; Zhang, Zunzhen

    2016-02-01

    Although it is well documented that endoplasmic reticulum (ER) stress and mitochondrial dysfunction are associated with apoptosis, little is known about whether they are involved in the apoptotic cell death induced by resveratrol and arsenic trioxide (ATO) combination. In this study, we identified a series of sensitization effects of resveratrol on human lung adenocarcinoma A549 cells to ATO treatment, with the combination index (CI) of resveratrol and ATO less than 1. Then, we demonstrated that ER stress was contributed to this synergistic effect, which was manifested by increased the expression levels of ER stress hallmarks, including 78-kDa glucose-regulated protein (GRP 78), caspase 12 and C/EBP-homologous protein (CHOP), In addition, mitochondrial dysfunction was observed after exposure of A549 cells to resveratrol or/and ATO, which was displayed by some alterations of mitochondria-related events, such as loss of mitochondrial membrane potential, cytochrome c release and changes of Bax and Bcl-2 expressions. Our results further demonstrated that resveratrol and ATO-induced ER stress and mitochondrial dysfunction were mediated by reactive oxygen species (ROS), showing that pre-treatment of N-acetyl-l-cysteine, a potent ROS scavenger, restored the ER stress and mitochondrial dysfunction in cells co-treated with resveratrol and ATO, thereby leading to the reduction of the apoptosis. Collectively, these results clearly suggest that ROS-mediated ER stress and mitochondrial dysfunction were involved in the apoptosis induced by resveratrol and ATO in A549 cells, which provides a novel insight into the molecular mechanisms of resveratrol-mediated ATO-sensitization.

  20. All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis

    PubMed Central

    Ma, Yafang; Liu, Lu; Jin, Jie; Lou, Yinjun

    2016-01-01

    Background Recently, the all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL), but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL. Methods We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity. Results Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22–0.67, p = 0.009), overall survival (HR = 0.44, 95% CI: 0.24–0.82, p = 0.009), complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01–1.10; p = 0.03). There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22–1.05; p = 0.07). Conclusion Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients. PMID:27391027

  1. Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity.

    PubMed

    Vineetha, Vadavanath Prabhakaran; Girija, Seetharaman; Soumya, Rema Sreenivasan; Raghu, Kozhiparambil Gopalan

    2014-03-01

    Evidences suggest that apple peel has a wide range of polyphenols having antioxidant activity and its consumption has been linked with improved health benefits. Arsenic trioxide (ATO) is a very effective drug for the treatment of acute promyelocytic leukemia (APL) but it leads to cardiotoxicity mediated through alterations in various cardiac ion channels and by increasing the intracellular calcium level and reactive oxygen species (ROS). The aim of the present investigation was to study the effect of methanolic extract of apple peel (APME) and aqueous extract of apple peel (APAE) on ATO (5 μM) induced toxicity in the H9c2 cardiac myoblast cell line. We estimated the cellular status of innate antioxidant enzymes, level of ROS, mitochondrial superoxide, glutathione and intracellular calcium with ATO and apple peel extracts. Prior to the cell line based study, we had evaluated the antioxidant potential of apple peel extract by 1,1-diphenyl-2-picrylhydrazyl (DPPH), total reducing power (TRP), superoxide anion and hydroxyl radical scavenging activity, in addition to quantifying total phenolic and flavonoid content. Both the extracts showed considerable antioxidant activity in cell-free chemical assays. In addition, both APME and APAE prevented the alteration in antioxidant status induced by ATO in H9c2 cells. Significant differential alterations had been observed in the activity of lactate dehydrogenase, superoxide dismutase, catalase, glutathione, glutathione peroxidase, thioredoxin reductase, xanthine oxidase, calcium overload and caspase 3 activity with ATO. The overall result revealed the protective property of polyphenol-rich apple peel extract against ATO induced cardiac toxicity via its antioxidant activity.

  2. Comparison of Optical and Power Doppler Ultrasound Imaging for Non-Invasive Evaluation of Arsenic Trioxide as a Vascular Disrupting Agent in Tumors

    PubMed Central

    Alhasan, Mustafa K.; Liu, Li; Lewis, Matthew A.; Magnusson, Jennifer; Mason, Ralph P.

    2012-01-01

    Small animal imaging provides diverse methods for evaluating tumor growth and acute response to therapy. This study compared the utility of non-invasive optical and ultrasound imaging to monitor growth of three diverse human tumor xenografts (brain U87-luc-mCherry, mammary MCF7-luc-mCherry, and prostate PC3-luc) growing in nude mice. Bioluminescence imaging (BLI), fluorescence imaging (FLI), and Power Doppler ultrasound (PD US) were then applied to examine acute vascular disruption following administration of arsenic trioxide (ATO). During initial tumor growth, strong correlations were found between manual caliper measured tumor volume and FLI intensity, BLI intensity following luciferin injection, and traditional B-mode US. Administration of ATO to established U87 tumors caused significant vascular shutdown within 2 hrs at all doses in the range 5 to 10 mg/kg in a dose dependant manner, as revealed by depressed bioluminescent light emission. At lower doses substantial recovery was seen within 4 hrs. At 8 mg/kg there was >85% reduction in tumor vascular perfusion, which remained depressed after 6 hrs, but showed some recovery after 24 hrs. Similar response was observed in MCF7 and PC3 tumors. Dynamic BLI and PD US each showed similar duration and percent reductions in tumor blood flow, but FLI showed no significant changes during the first 24 hrs. The results provide further evidence for comparable utility of optical and ultrasound imaging for monitoring tumor growth, More specifically, they confirm the utility of BLI and ultrasound imaging as facile assays of the vascular disruption in solid tumors based on ATO as a model agent. PMID:23029403

  3. Arsenic trioxide induces apoptosis of human monocytes during macrophagic differentiation through nuclear factor-kappaB-related survival pathway down-regulation.

    PubMed

    Lemarie, Anthony; Morzadec, Claudie; Mérino, Delphine; Micheau, Olivier; Fardel, Olivier; Vernhet, Laurent

    2006-01-01

    Arsenic trioxide (As(2)O(3)) is known to be toxic toward leukemia cells. In this study, we determined its effects on survival of human monocytic cells during macrophagic differentiation, an important biological process involved in the immune response. As(2)O(3) used at clinically relevant pharmacological concentrations induced marked apoptosis of human blood monocytes during differentiation with either granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor. Apoptosis of monocytes was associated with increased caspase activities and decreased DNA binding of p65 nuclear factor-kappaB (NF-kappaB); like As(2)O(3), the selective NF-kappaB inhibitor (E)-3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (Bay 11-7082) strongly reduced survival of differentiating monocytes. The role of NF-kappaB in arsenic toxicity was also studied in promonocytic U937 cells during phorbol 12-myristate 13-acetate-induced macrophagic differentiation. In these cells, As(2)O(3) first reduced DNA binding of p65 NF-kappaB and subsequently induced apoptosis. In addition, overexpression of the p65 NF-kappaB subunit, following stable infection with a p65 retroviral expressing vector, increased survival of As(2)O(3)-treated U937 cells. As(2)O(3) specifically decreased protein levels of X-linked inhibitor of apoptosis protein and FLICE-inhibitory protein, two NF-kappaB-regulated genes in both U937 cells and blood monocytes during their differentiations. Finally, As(2)O(3) was found to inhibit macrophagic differentiation of monocytic cells when used at cytotoxic concentrations; however, overexpression of the p65 NF-kappaB subunit in U937 cells reduced its effects toward differentiation. In contrast to monocytes, well differentiated macrophages were resistant to low concentrations of As(2)O(3). Altogether, our study demonstrates that clinically relevant concentrations of As(2)O(3) induced marked apoptosis of monocytic cells during in vitro macrophagic differentiation

  4. TG-interacting factor transcriptionally induced by AKT/FOXO3A is a negative regulator that antagonizes arsenic trioxide-induced cancer cell apoptosis

    SciTech Connect

    Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling; Yeh, Bi-Wen; Wu, Wen-Jeng; Huang, Huei-Sheng

    2015-05-15

    Arsenic trioxide (ATO) is a multi-target drug approved by the Food and Drug Administration as the first-line chemotherapeutic agent for the treatment of acute promyelocytic leukemia. In addition, several clinical trials are being conducted with arsenic-based drugs for the treatment of other hematological malignancies and solid tumors. However, ATO's modest clinical efficacy on some cancers, and potential toxic effects on humans have been reported. Determining how best to reduce these adverse effects while increasing its therapeutic efficacy is obviously a critical issue. Previously, we demonstrated that the JNK-induced complex formation of phosphorylated c-Jun and TG-interacting factor (TGIF) antagonizes ERK-induced cyclin-dependent kinase inhibitor CDKN1A (p21{sup WAF1/CIP1}) expression and resultant apoptosis in response to ATO in A431 cells. Surprisingly, at low-concentrations (0.1–0.2 μM), ATO increased cellular proliferation, migration and invasion, involving TGIF expression, however, at high-concentrations (5–20 μM), ATO induced cell apoptosis. Using a promoter analysis, TGIF was transcriptionally regulated by ATO at the FOXO3A binding site (− 1486 to − 1479 bp) via the c-Src/EGFR/AKT pathway. Stable overexpression of TGIF promoted advancing the cell cycle into the S phase, and attenuated 20 μM ATO-induced apoptosis. Furthermore, blockage of the AKT pathway enhanced ATO-induced CDKN1A expression and resultant apoptosis in cancer cells, but overexpression of AKT1 inhibited CDKN1A expression. Therefore, we suggest that TGIF is transcriptionally regulated by the c-Src/EGFR/AKT pathway, which plays a role as a negative regulator in antagonizing ATO-induced CDKN1A expression and resultant apoptosis. Suppression of these antagonistic effects might be a promising therapeutic strategy toward improving clinical efficacy of ATO. - Highlights: • ATO-induced biphasic survival responses of cancer cells depend on low- or high-concentrations. • TGIF mediates

  5. Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL).

    PubMed

    Kchour, Ghada; Tarhini, Mahdi; Kooshyar, Mohamad-Mehdi; El Hajj, Hiba; Wattel, Eric; Mahmoudi, Mahmoud; Hatoum, Hassan; Rahimi, Hossein; Maleki, Masoud; Rafatpanah, Houshang; Rezaee, S A Rahim; Yazdi, Mojtaba Tabatabaei; Shirdel, Abbas; de Thé, Hugues; Hermine, Olivier; Farid, Reza; Bazarbachi, Ali

    2009-06-25

    Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-kappaB activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy.

  6. The clinical activity of arsenic trioxide, ascorbic acid, ifosfamide and prednisone combination therapy in patients with relapsed and refractory multiple myeloma

    PubMed Central

    Li, Xin; Sun, Wan-Jun

    2015-01-01

    This study aimed to investigate the activity of arsenic trioxide (As2O3) combined with ascorbic acid, ifosfamide, and prednisone chemotherapy in patients with repeatedly relapsed and refractory multiple myeloma (MM). Here, we retrospectively analyzed medical data of 30 MM patients showing progressive disease after receiving at least two previous lines of treatment including an immunomodulatory agent (thalidomide or lenalidomide) and a proteasome inhibitor. There were 19 men and eleven women, aged 54–73 (median 65) years, in this study. The distribution of different isotypes included immunoglobulin G(IgG) (12 patients), IgA (six patients), IgD (three), and light chain (nine patients). All the patients were Durie–Salmon stage III and had relapsed at least three times; the median cycles of prior therapies was 15 (range 10–18). The patients were treated with As2O3, ascorbic acid, and CP (ifosfamide 1 g on day 1, day 3, day 5, and day 7; prednisone 30 mg taken orally for 2 weeks). As2O3 was administered as an intravenous infusion at a dose of 10 mg/d and ascorbic acid at a dose of 2 g/d for 14 days of each 4-week cycle. The results showed that after 2 cycles of therapy, there were five patients that attained partial response, 15 had minimal response, five had no change, and five had progressive disease. The overall response rate was 66.7% (20/30 cases), 50% (10/20 cases), and 40% (2/5 cases), respectively, after 2, 4, and 6 cycles of the therapy. But there were no patients that attained complete remission. The median time of overall survival and progression-free survival were 48 (29–120) and 6 (2–8) months, respectively. The most common treatment-related adverse events included neutropenia, fatigue, anemia, thrombocytopenia, and infection that could be tolerated. The results showed that As2O3 combined with ascorbic acid, ifosfamide, and prednisone chemotherapy may be a choice treatment for repeatedly relapsed and refractory MM patients. PMID:25914547

  7. Budgetary impact of treating acute promyelocytic leukemia patients with first-line arsenic trioxide and retinoic acid from an Italian payer perspective.

    PubMed

    Kruse, Morgan; Wildner, Rebecca; Barnes, Gisoo; Martin, Monique; Mueller, Udo; Lo-Coco, Francesco; Pathak, Ashutosh

    2015-01-01

    The objective of this study was to estimate the net cost of arsenic trioxide (ATO) added to all-trans retinoic acid (ATRA) compared to ATRA plus chemotherapy when used in first-line acute promyelocytic leukemia (APL) treatment for low to intermediate risk patients from the perspective of the overall Italian healthcare systemA Markov model was developed with 3 health states: stable disease, disease event and death. Each month, patients could move from stable to disease event or die from either state. After a disease event, patients discontinued initial treatment and switched to the other regimen as second-line therapy. Treatment regimens, efficacy and adverse events were derived from published sources and expert opinion; unit costs were collected from standard Italian sources. Clinical outcomes and costs for pre-ATO and post-ATO scenarios were combined with population and product utilization information to calculate the total budgetary impact using a 3-year time horizon; one-way sensitivity analyses were conducted. Three-year cumulative pharmacy costs for ATO+ATRA were €46,700 per-patient versus €6,500 for ATRA+chemotherapy; however, medical costs for ATO+ATRA were €12,300 per-patient versus €30,200 for ATRA+chemotherapy. The total budgetary impact was estimated to be an additional €127,300, €312,500 and €477,800 in the first, second and third years, respectively. The model was most sensitive to changes in the cost of the ATO+ATRA regimen during the consolidation phase. Budgetary impact models are valuable to payers making formulary decisions regarding the access and affordability of new medicines. The cost of treatment analysis showed that pharmacy costs for ATO+ATRA were higher than for ATRA+chemotherapy, while all other evaluated costs were lower for ATO+ATRA treated patients. The average budgetary impact was €305,900 per year overall, representing a 3.5% increase. Further research is needed to determine the cost-effectiveness of ATO+ATRA compared

  8. Apoptotic Efficacy of Etomoxir in Human Acute Myeloid Leukemia Cells. Cooperation with Arsenic Trioxide and Glycolytic Inhibitors, and Regulation by Oxidative Stress and Protein Kinase Activities

    PubMed Central

    Estañ, María Cristina; Calviño, Eva; Calvo, Susana; Guillén-Guío, Beatriz; Boyano-Adánez, María del Carmen; de Blas, Elena; Rial, Eduardo; Aller, Patricio

    2014-01-01

    Fatty acid synthesis and oxidation are frequently exacerbated in leukemia cells, and may therefore represent a target for therapeutic intervention. In this work we analyzed the apoptotic and chemo-sensitizing action of the fatty acid oxidation inhibitor etomoxir in human acute myeloid leukemia cells. Etomoxir caused negligible lethality at concentrations up to 100 µM, but efficaciously cooperated to cause apoptosis with the anti-leukemic agent arsenic trioxide (ATO, Trisenox), and with lower efficacy with other anti-tumour drugs (etoposide, cisplatin), in HL60 cells. Etomoxir-ATO cooperation was also observed in NB4 human acute promyelocytic cells, but not in normal (non-tumour) mitogen-stimulated human peripheral blood lymphocytes. Biochemical determinations in HL60 cells indicated that etomoxir (25–200 µM) dose-dependently inhibited mitochondrial respiration while slightly stimulating glycolysis, and only caused marginal alterations in total ATP content and adenine nucleotide pool distribution. In addition, etomoxir caused oxidative stress (increase in intracellular reactive oxygen species accumulation, decrease in reduced glutathione content), as well as pro-apoptotic LKB-1/AMPK pathway activation, all of which may in part explain the chemo-sensitizing capacity of the drug. Etomoxir also cooperated with glycolytic inhibitors (2-deoxy-D-glucose, lonidamine) to induce apoptosis in HL60 cells, but not in NB4 cells. The combined etomoxir plus 2-deoxy-D-glucose treatment did not increase oxidative stress, caused moderate decrease in net ATP content, increased the AMP/ATP ratio with concomitant drop in energy charge, and caused defensive Akt and ERK kinase activation. Apoptosis generation by etomoxir plus 2-deoxy-D-glucose was further increased by co-incubation with ATO, which is apparently explained by the capacity of ATO to attenuate Akt and ERK activation. In summary, co-treatment with etomoxir may represent an interesting strategy to increase the apoptotic

  9. 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 ...

  10. Induction of the mesenchymal to epithelial transition by demethylation- activated microRNA-200c is involved in the anti-migration/invasion effects of arsenic trioxide on human breast cancer cells.

    PubMed

    Si, Lu; Jiang, Fei; Li, Yuan; Ye, Xianqing; Mu, Juan; Wang, Xingxing; Ning, Shilong; Hu, Chunyan; Li, Zhong

    2015-09-01

    Breast cancer is a major health problem worldwide. Current standard practices for treatment of breast cancer are less than satisfactory because of high rates of metastasis. Arsenic trioxide (As(2)O(3)), which induces demethylation of DNA and causes apoptosis, has been used as an anti-tumor agent. Little is known, however, regarding its anti-metastatic effects. The microRNA-200c (miR-200c), which is frequently lowly expressed in triple negative breast cancers (TNBCs), inhibits metastasis by inducing the mesenchymal to epithelial transition (MET). Here, we report that As(2)O(3) attenuates the migratory and invasive capacities of breast cancer cells, MDA-MB-231 and BT-549. Notably, As(2)O(3) induces an MET in vitro and in vivo, as determined by the increased expression of the epithelial marker, E-cadherin and decreased expressions of mesenchymal markers, N-cadherin and vimentin. Moreover, As(2)O(3) up-regulates the expression of miR-200c through demethylation. Over-expression of miR-200c enhances the expression of E-cadherin and decreases the expressions of N-cadherin and vimentin. Further, in MDA-MB-231 cells exposed to As(2)O(3), knockdown of miR-200c blocks the As(2)O(3) -induced MET. Finally, in MDA-MB-231 and BT-549 cells exposed to As(2)O(3), knockdown of miR-200c decreases the As(2)O(3) -induced inhibition of the migratory and invasive capacities. By identifying a mechanism whereby As(2)O(3) regulates miR-200c and MET, the results establish the anti-migration/invasion potential of arsenic trioxide.

  11. Anti-cancer drugs interfere with intracellular calcium signaling.

    PubMed

    Florea, Ana-Maria; Büsselberg, Dietrich

    2009-09-01

    (Neuro-)toxicity of metal and metal compounds is frequently highlighted. While specific metals or metal compounds are essential for cellular function, other metals are toxic and/or carcinogens. Metals can trigger accidental cell death in the form of necrosis, or activate programmed cell death in the form of apoptosis. The aim of anti-cancer therapy is induction of apoptosis in tumor cells. Therefore, there is an interesting twist in the toxicity of metals and metal compounds (e.g., arsenic trioxide, cisplatin); since they have a higher specificity to induce apoptosis in cancer cells (possibly due to the high turnover in these cells) they are used to cure some forms of cancer. A body of evidence suggests that second messengers, such as modulations in the intracellular calcium concentration, could be involved in metals induced toxicity as well as in the beneficial effects shown by anti-cancer drugs. Here we review the influence on calcium homeostasis induced by some metallic compounds: cisplatin, arsenic trioxide and trimethyltin chloride.

  12. Acute arsenic ingestion.

    PubMed

    Levin-Scherz, J K; Patrick, J D; Weber, F H; Garabedian, C

    1987-06-01

    A 21-year-old man presented in shock after ingesting 2 g of arsenic trioxide. He died within 37 hours despite intensive treatment that included intramuscular dimercaprol and hemodialysis. Hemodynamic and laboratory data are presented illustrating the multisystem toxicities of inorganic arsenic. Hemodialysis, previously described as an effective therapeutic adjunct, was shown to be ineffective in this case.

  13. [Acute arsenic poisoning].

    PubMed

    Montelescaut, Etienne; Vermeersch, Véronique; Commandeur, Diane; Huynh, Sophie; Danguy des Deserts, Marc; Sapin, Jeanne; Ould-Ahmed, Mehdi; Drouillard, Isabelle

    2014-01-01

    Acute arsenic poisoning is a rare cause of suicide attempt. It causes a multiple organs failure caused by cardiogenic shock. We report the case of a patient admitted twelve hours after an ingestion of trioxide arsenic having survived thanks to a premature treatment.

  14. [Acute arsenic poisoning].

    PubMed

    Montelescaut, Etienne; Vermeersch, Véronique; Commandeur, Diane; Huynh, Sophie; Danguy des Deserts, Marc; Sapin, Jeanne; Ould-Ahmed, Mehdi; Drouillard, Isabelle

    2014-01-01

    Acute arsenic poisoning is a rare cause of suicide attempt. It causes a multiple organs failure caused by cardiogenic shock. We report the case of a patient admitted twelve hours after an ingestion of trioxide arsenic having survived thanks to a premature treatment. PMID:25486670

  15. PREPARATION OF URANIUM TRIOXIDE

    DOEpatents

    Buckingham, J.S.

    1959-09-01

    The production of uranium trioxide from aqueous solutions of uranyl nitrate is discussed. The uranium trioxide is produced by adding sulfur or a sulfur-containing compound, such as thiourea, sulfamic acid, sulfuric acid, and ammonium sulfate, to the uranyl solution in an amount of about 0.5% by weight of the uranyl nitrate hexahydrate, evaporating the solution to dryness, and calcining the dry residue. The trioxide obtained by this method furnished a dioxide with a considerably higher reactivity with hydrogen fluoride than a trioxide prepared without the sulfur additive.

  16. Novel human neutrophil agonistic properties of arsenic trioxide: involvement of p38 mitogen-activated protein kinase and/or c-jun NH2-terminal MAPK but not extracellular signal-regulated kinases-1/2.

    PubMed

    Binet, François; Girard, Denis

    2008-12-01

    Arsenic trioxide (ATO) is known for treating acute promyelocytic leukemia and for inducing apoptosis and mitogen-activated protein kinases (MAPKs) in promyelocytes and cancer cells. We recently reported that ATO induces neutrophil apoptosis. The aim of this study was to establish whether or not ATO recruits MAPKs in neutrophils, as well as to further investigate its agonistic properties. We found that ATO activates p38 and that, unlike H2O2, this response was not inhibited by exogenous catalase. Also, we demonstrated that ATO-induced p38 activation occurs before H2O2 generation and without a calcium burst. We next established that ATO recruits c-jun NH2-terminal (JNK) but not extracellular signal-regulated kinase 1 and 2 (Erk-1/2). Using pharmacological inhibitors, we found that the proapoptotic activity of ATO occurs by a MAPK-independent mechanism. In contrast, the ability of ATO to enhance adhesion, migration, phagocytosis, release, and activity of gelatinase and degranulation of secretory, specific, and gelatinase, but not azurophilic granules, is dependent upon activation of p38 and/or JNK. This is the first study establishing that ATO possesses important agonistic properties in human neutrophils. Given the central role of neutrophils in various inflammatory disorders, we propose that ATO might have broader therapeutic implications in clinics, especially for regulating inflammation.

  17. Arsenic

    MedlinePlus

    ... mainly found in its less toxic organic form. Industrial processes Arsenic is used industrially as an alloying ... are also required to reduce occupational exposure from industrial processes. Education and community engagement are key factors ...

  18. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  19. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  20. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  1. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  2. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  3. Arsenic cardiotoxicity: An overview.

    PubMed

    Alamolhodaei, Nafiseh Sadat; Shirani, Kobra; Karimi, Gholamreza

    2015-11-01

    Arsenic, a naturally ubiquitous element, is found in foods and environment. Cardiac dysfunction is one of the major causes of morbidity and mortality in the world. Arsenic exposure is associated with various cardiopathologic effects including ischemia, arrhythmia and heart failure. Possible mechanisms of arsenic cardiotoxicity include oxidative stress, DNA fragmentation, apoptosis and functional changes of ion channels. Several evidences have shown that mitochondrial disruption, caspase activation, MAPK signaling and p53 are the pathways for arsenic induced apoptosis. Arsenic trioxide is an effective and potent antitumor agent used in patients with acute promyelocytic leukemia and produces dramatic remissions. As2O3 administration has major limitations such as T wave changes, QT prolongation and sudden death in humans. In this review, we discuss the underlying pathobiology of arsenic cardiotoxicity and provide information about cardiac health effects associated with some medicinal plants in arsenic toxicity.

  4. Oxidative stress-mediated intrinsic apoptosis in human promyelocytic leukemia HL-60 cells induced by organic arsenicals

    PubMed Central

    Fan, Xiao-Yang; Chen, Xin-You; Liu, Yu-Jiao; Zhong, Hui-Min; Jiang, Feng-Lei; Liu, Yi

    2016-01-01

    Arsenic trioxide has shown the excellent therapeutic efficiency for acute promyelocytic leukemia. Nowadays, more and more research focuses on the design of the arsenic drugs, especially organic arsenicals, and on the mechanism of the inducing cell death. Here we have synthesized some organic arsenicals with Schiff base structure, which showed a better antitumor activity for three different kinds of cancer cell lines, namely HL-60, SGC 7901 and MCF-7. Compound 2a (2-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) and 2b (2-methoxy-4-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) were chosen for further mechanism study due to their best inhibitory activities for HL-60 cells, of which the half inhibitory concentration (IC50) were 0.77 μM and 0.51 μM, respectively. It was illustrated that 2a or 2b primarily induced the elevation of reactive oxygen species, decrease of glutathione level, collapse of mitochondrial membrane potential, release of cytochrome c, activation of Caspase-3 and apoptosis, whereas all of the phenomena can be eliminated by the addition of antioxidants. Therefore, we concluded that compound 2a and 2b can induce the oxidative stress-mediated intrinsic apoptosis in HL-60 cells. Both the simplicity of structure with Schiff base group and the better anticancer efficiency demonstrate that organic arsenicals are worthy of further exploration as a class of potent antitumor drugs. PMID:27432798

  5. Industrial contributions of arsenic to the environment.

    PubMed

    Nelson, K W

    1977-08-01

    Arsenic is present in all copper, lead, and zinc sulfide ores and is carried along with those metals in the mining, milling and concentrating process. Separation, final concentration and refining of by-product arsenic as the trioxide is achieved at smelters. Arsenic is the essential consistent element of many compounds important and widely used in agriculture and wood preservation. Lesser amounts are used in metal alloys, glass-making, and feed additives. There is no significant recycling. Current levels of arsenic emissions to the atmosphere from smelters and power plants and ambient air concentrations are given as data of greatest environmental interest. PMID:908308

  6. Acute and chronic arsenic toxicity.

    PubMed

    Ratnaike, R N

    2003-07-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water.

  7. Acute and chronic arsenic toxicity

    PubMed Central

    Ratnaike, R

    2003-01-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water. PMID:12897217

  8. A biography of arsenic and medicine in Hong Kong and China.

    PubMed

    Au, W Y

    2011-12-01

    Arsenic trioxide has been used in traditional Chinese medicine for over 5000 years, but lost its appeal due to its toxicity. It was rediscovered in western medicine and enjoyed a renaissance from 1830 to 1930, as the first effective chemotherapy against syphilis, parasites and leukaemia. These years were also a time of political turmoil in China. The Nanking treaty (29 August 1842) turned Hong Kong into a colony, while the Xinhai Revolution (10 October 1911) gave birth to a republic of China. Arsenic returned to China and Hong Kong with the establishment of the first medical schools from 1887 to 1920. Until 1950, oral arsenic trioxide was the standard anti-leukaemic treatment in Queen Mary Hospital. The advent of alkylating chemotherapeutic agents replaced arsenic trioxide in Hong Kong and around the world. In the 1970s, however, the specific activity of arsenic trioxide against acute promyelocytic leukaemia was re-discovered during the Cultural Revolution in Harbin, China. In 1997, Hong Kong was returned to China. In the same year, arsenic trioxide returned to the world stage. Intravenous arsenic trioxide became the worldwide standard therapy for relapsed acute promyelocytic leukaemia. Oral administration of arsenic trioxide was revived in Hong Kong in 2000. This resulted in the first locally produced, registered, patented prescription drug in Hong Kong. Pending imminent manufacture, this product is poised to revolutionise acute promyelocytic leukaemia care and may hold the key to saving the lives of acute promyelocytic leukaemia patients worldwide. The remarkable journey of arsenic in the setting of medical history of China and Hong Kong is reviewed.

  9. A biography of arsenic and medicine in Hong Kong and China.

    PubMed

    Au, W Y

    2011-12-01

    Arsenic trioxide has been used in traditional Chinese medicine for over 5000 years, but lost its appeal due to its toxicity. It was rediscovered in western medicine and enjoyed a renaissance from 1830 to 1930, as the first effective chemotherapy against syphilis, parasites and leukaemia. These years were also a time of political turmoil in China. The Nanking treaty (29 August 1842) turned Hong Kong into a colony, while the Xinhai Revolution (10 October 1911) gave birth to a republic of China. Arsenic returned to China and Hong Kong with the establishment of the first medical schools from 1887 to 1920. Until 1950, oral arsenic trioxide was the standard anti-leukaemic treatment in Queen Mary Hospital. The advent of alkylating chemotherapeutic agents replaced arsenic trioxide in Hong Kong and around the world. In the 1970s, however, the specific activity of arsenic trioxide against acute promyelocytic leukaemia was re-discovered during the Cultural Revolution in Harbin, China. In 1997, Hong Kong was returned to China. In the same year, arsenic trioxide returned to the world stage. Intravenous arsenic trioxide became the worldwide standard therapy for relapsed acute promyelocytic leukaemia. Oral administration of arsenic trioxide was revived in Hong Kong in 2000. This resulted in the first locally produced, registered, patented prescription drug in Hong Kong. Pending imminent manufacture, this product is poised to revolutionise acute promyelocytic leukaemia care and may hold the key to saving the lives of acute promyelocytic leukaemia patients worldwide. The remarkable journey of arsenic in the setting of medical history of China and Hong Kong is reviewed. PMID:22147326

  10. Inorganic arsenic toxicosis in a beef herd.

    PubMed

    Faires, Meredith C

    2004-04-01

    Over a 44-day period, 4 of 5 affected calves in a 170-head herd of beef cattle died after exhibiting clinical signs of lethargy, ataxia, anorexia, and diarrhea. Histopathological examination of tissues and toxicological analysis of a suspicious powder discovered in the pasture confirmed arsenic trioxide toxicosis.

  11. Peripheral neuropathy in arsenic smelter workers.

    PubMed

    Feldman, R G; Niles, C A; Kelly-Hayes, M; Sax, D S; Dixon, W J; Thompson, D J; Landau, E

    1979-07-01

    We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.

  12. Arsenic round the world: a review.

    PubMed

    Mandal, Badal Kumar; Suzuki, Kazuo T

    2002-08-16

    This review deals with environmental origin, occurrence, episodes, and impact on human health of arsenic. Arsenic, a metalloid occurs naturally, being the 20th most abundant element in the earth's crust, and is a component of more than 245 minerals. These are mostly ores containing sulfide, along with copper, nickel, lead, cobalt, or other metals. Arsenic and its compounds are mobile in the environment. Weathering of rocks converts arsenic sulfides to arsenic trioxide, which enters the arsenic cycle as dust or by dissolution in rain, rivers, or groundwater. So, groundwater contamination by arsenic is a serious threat to mankind all over the world. It can also enter food chain causing wide spread distribution throughout the plant and animal kingdoms. However, fish, fruits, and vegetables primarily contain organic arsenic, less than 10% of the arsenic in these foods exists in the inorganic form, although the arsenic content of many foods (i.e. milk and dairy products, beef and pork, poultry, and cereals) is mainly inorganic, typically 65-75%. A few recent studies report 85-95% inorganic arsenic in rice and vegetables, which suggest more studies for standardisation. Humans are exposed to this toxic arsenic primarily from air, food, and water. Thousands and thousands of people are suffering from the toxic effects of arsenicals in many countries all over the world due to natural groundwater contamination as well as industrial effluent and drainage problems. Arsenic, being a normal component of human body is transported by the blood to different organs in the body, mainly in the form of MMA after ingestion. It causes a variety of adverse health effects to humans after acute and chronic exposures such as dermal changes (pigmentation, hyperkeratoses, and ulceration), respiratory, pulmonary, cardiovascular, gastrointestinal, hematological, hepatic, renal, neurological, developmental, reproductive, immunologic, genotoxic, mutagenetic, and carcinogenic effects. Key research

  13. Arsenic round the world: a review.

    PubMed

    Mandal, Badal Kumar; Suzuki, Kazuo T

    2002-08-16

    This review deals with environmental origin, occurrence, episodes, and impact on human health of arsenic. Arsenic, a metalloid occurs naturally, being the 20th most abundant element in the earth's crust, and is a component of more than 245 minerals. These are mostly ores containing sulfide, along with copper, nickel, lead, cobalt, or other metals. Arsenic and its compounds are mobile in the environment. Weathering of rocks converts arsenic sulfides to arsenic trioxide, which enters the arsenic cycle as dust or by dissolution in rain, rivers, or groundwater. So, groundwater contamination by arsenic is a serious threat to mankind all over the world. It can also enter food chain causing wide spread distribution throughout the plant and animal kingdoms. However, fish, fruits, and vegetables primarily contain organic arsenic, less than 10% of the arsenic in these foods exists in the inorganic form, although the arsenic content of many foods (i.e. milk and dairy products, beef and pork, poultry, and cereals) is mainly inorganic, typically 65-75%. A few recent studies report 85-95% inorganic arsenic in rice and vegetables, which suggest more studies for standardisation. Humans are exposed to this toxic arsenic primarily from air, food, and water. Thousands and thousands of people are suffering from the toxic effects of arsenicals in many countries all over the world due to natural groundwater contamination as well as industrial effluent and drainage problems. Arsenic, being a normal component of human body is transported by the blood to different organs in the body, mainly in the form of MMA after ingestion. It causes a variety of adverse health effects to humans after acute and chronic exposures such as dermal changes (pigmentation, hyperkeratoses, and ulceration), respiratory, pulmonary, cardiovascular, gastrointestinal, hematological, hepatic, renal, neurological, developmental, reproductive, immunologic, genotoxic, mutagenetic, and carcinogenic effects. Key research

  14. ARSENIC EFFECTS ON TELOMERE AND TELOMERASE ACTIVITY

    EPA Science Inventory

    Arsenic effects on telomere and telomerase activity. T-C. Zhang, M. T. Schmitt, J. Mo, J. L. Mumford, National Research Council and U.S Environmental Protection Agency, NHEERL, Research Triangle Park, NC 27711
    Arsenic is a known carcinogen and also an anticancer agent for acut...

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

    PubMed Central

    Farmer, J G; Johnson, L R

    1990-01-01

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

  16. The evolving use of arsenic in pharmacotherapy of malignant disease.

    PubMed

    Kritharis, Athena; Bradley, Thomas P; Budman, Daniel R

    2013-06-01

    For more than 2,000 years, arsenic and its derivatives have shown medical utility. Owing to the toxicities and potential carcinogenicity of arsenicals, their popularity has fluctuated. The exact mechanism of action of therapeutic arsenic is not well characterized but likely to involve apoptosis, generation of reactive oxygen species, inhibition of intracellular transduction pathways, and cell functions. Arsenic trioxide has received approval for use in patients with relapsed acute promyelocytic leukemia for remission induction. Arsenic has additionally shown activity in a range of solid tumors, myelodysplastic syndrome, multiple myeloma, and in autoimmune diseases. The following is a review of the history of arsenic, its cellular metabolism, pharmacology, genetic basis of disposition, associated toxicities, and clinical efficacy.

  17. The evolving use of arsenic in pharmacotherapy of malignant disease.

    PubMed

    Kritharis, Athena; Bradley, Thomas P; Budman, Daniel R

    2013-06-01

    For more than 2,000 years, arsenic and its derivatives have shown medical utility. Owing to the toxicities and potential carcinogenicity of arsenicals, their popularity has fluctuated. The exact mechanism of action of therapeutic arsenic is not well characterized but likely to involve apoptosis, generation of reactive oxygen species, inhibition of intracellular transduction pathways, and cell functions. Arsenic trioxide has received approval for use in patients with relapsed acute promyelocytic leukemia for remission induction. Arsenic has additionally shown activity in a range of solid tumors, myelodysplastic syndrome, multiple myeloma, and in autoimmune diseases. The following is a review of the history of arsenic, its cellular metabolism, pharmacology, genetic basis of disposition, associated toxicities, and clinical efficacy. PMID:23494203

  18. Arsenic in rain and the Atmospheric mass balance of arsenic

    NASA Astrophysics Data System (ADS)

    Andreae, Meinrat O.

    1980-08-01

    An attempt to construct a mass balance of arsenic in the world atmosphere showed that the published data on arsenic concentrations in rain were not compatible with measured values of atmospheric concentrations at remote sites and with estimates of arsenic fluxes into the atmosphere. To resolve this problem, samples of rainwater and snow from eight sites in California, Washington, and Hawaii were analyzed for arsenite, arsenate, and methylated forms of arsenic. The inorganic species were detectable in most samples, but no methylated forms were present above the detection limit of 0.2 ppt. Between October 1976 and March 1978, 43 samples of rain were collected at three locations near the coast in La Jolla. No significant differences between these sites were evident. The average concentration, weighted for rainfall amounts, was 0.007 ppb arsenite and 0.012 ppb arsenate, giving a total concentration of 0.019 ppb As. The samples from Kauai gave an average total arsenic identical to that from La Jolla. This suggests that the La Jolla samples, most of which were collected during strong onshore flow of air from the Pacific, represent very clean air. During some periods of pollutant buildup, values up to 0.59 ppb were found in La Jolla. In a few samples, on the other hand, the arsenic concentrations were below the detection limit of 0.004 ppb. Comparable values were also found in samples of snow from Norden, California, a site at 2225 m elevation in the Sierra Nevada. These values fit well with concentrations modeled on the basis of aerosol analyses from remote sites. The average arsenic concentration at Anacortes Island, Washington, was significantly higher: 1.06 ppb with 88% of the arsenic in the form of arsenite. This value can be explained by a Gaussian plume model with the Tacoma smelter at its origin. This plant, which is 154 krn from the sampling site, emits ˜180 kg of arsenic per day in the form of arsenic trioxide, which is transported northward by the prevailing

  19. Determination of sulfur trioxide in engine exhaust.

    PubMed

    Arnold, D R

    1975-04-01

    Sulfur trioxide in the exhaust gas of an internal combustion engine is removed and concentrated by absorption in a solution of 80% isopropyl alcohol, which quantitatively absorbs it and inhibits the oxidation of any sulfur dioxide which may be absorbed. The absorbed sulfur trioxide (sulfuric acid) is determined by an absorption titration by using barium chloride as the titrant and thorin as the indicator. The sulfur dioxide content of the exhaust is measured continuously by means of a DuPont Model 411 ultraviolet photoanalyzer.

  20. Determination of sulfur trioxide in engine exhaust.

    PubMed Central

    Arnold, D R

    1975-01-01

    Sulfur trioxide in the exhaust gas of an internal combustion engine is removed and concentrated by absorption in a solution of 80% isopropyl alcohol, which quantitatively absorbs it and inhibits the oxidation of any sulfur dioxide which may be absorbed. The absorbed sulfur trioxide (sulfuric acid) is determined by an absorption titration by using barium chloride as the titrant and thorin as the indicator. The sulfur dioxide content of the exhaust is measured continuously by means of a DuPont Model 411 ultraviolet photoanalyzer. PMID:50930

  1. Dissimilatory antimonate reduction and production of antimony trioxide microcrystals by a novel microorganism.

    PubMed

    Abin, Christopher A; Hollibaugh, James T

    2014-01-01

    Antimony (Sb) is a metalloid that has been exploited by humans since the beginning of modern civilization. The importance of Sb to such diverse industries as nanotechnology and health is underscored by the fact that it is currently the ninth-most mined metal worldwide. Although its toxicity mirrors that of its Group 15 neighbor arsenic, its environmental chemistry is very different, and, unlike arsenic, relatively little is known about the fate and transport of Sb, especially with regard to biologically mediated redox reactions. To further our understanding of the interactions between microorganisms and Sb, we have isolated a bacterium that is capable of using antimonate [Sb(V)] as a terminal electron acceptor for anaerobic respiration, resulting in the precipitation of antimonite [Sb(III)] as microcrystals of antimony trioxide. The bacterium, designated strain MLFW-2, is a sporulating member of a deeply branching lineage within the order Bacillales (phylum Firmicutes). This report provides the first unequivocal evidence that a bacterium is capable of conserving energy for growth and reproduction from the reduction of antimonate. Moreover, microbiological antimonate reduction may serve as a novel route for the production of antimony trioxide microcrystals of commercial significance to the nanotechnology industry.

  2. Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors

    NASA Astrophysics Data System (ADS)

    Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

    1995-03-01

    A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

  3. Cumulative exposure to arsenic and its relationship to respiratory cancer among copper smelter employees.

    PubMed

    Lee-Feldstein, A

    1986-04-01

    To explore the role of arsenic as a human carcinogen, the respiratory cancer mortality experience (1938 to 1977) of 8,045 while male smelter employees in Montana was examined relative to cumulative exposure to arsenic trioxide and was compared with that of the white male population of the same region. Exposure to arsenic was estimated for various work areas from industrial hygiene reports of average concentrations present in the smelter. Respiratory cancer mortality was analyzed further by time period of first employment and maximum lifetime exposure to arsenic trioxide. When exposure was estimated with arithmetic means of measured concentrations among men first employed prior to 1925, respiratory cancer mortality increased linearly with increasing cumulative exposure group, ranging from two to nine times expected; among those first employed in the period 1925 to 1947 it also increased linearly with increasing cumulative exposure group.

  4. [Noncirrhotic liver fibrosis after chronic arsenic poisoning].

    PubMed

    Piontek, M; Hengels, K J; Borchard, F; Strohmeyer, G

    1989-10-27

    A 67-year-old woman with portal hypertension, splenomegaly without portal vein thrombosis, leucopenia and thrombocytopenia of splenic origin had repeated episodes of life-threatening haemorrhage from esophageal varices. Since childhood she had suffered from psoriasis and had been treated over a period of 15 years with Fowler's solution (in all about 25 g of arsenic trioxide). She had the characteristic skin lesions of arsenical poisoning-palmar hyperkeratoses and two basal cell carcinomas on the trunk. Histological examination of a wedge biopsy from the liver showed definite structural changes with fibrosis around the central veins and in the portal tracts. There was no evidence of cirrhotic alteration. The hepatocytes were normal by light microscopy and electron microscopy. This case of noncirrhotic hepatic fibrosis is considered to have been caused by chronic arsenical poisoning.

  5. An arsenic fluorescent compound as a novel probe to study arsenic-binding proteins.

    PubMed

    Femia, A Lis; Temprana, C Facundo; Santos, Javier; Carbajal, María Laura; Amor, María Silvia; Grasselli, Mariano; Alonso, Silvia Del V

    2012-12-01

    Arsenic-binding proteins are under continuous research. Their identification and the elucidation of arsenic/protein interaction mechanisms are important because the biological effects of these complexes may be related not only to arsenic but also to the arsenic/protein structure. Although many proteins bearing a CXXC motif have been found to bind arsenic in vivo, new tools are necessary to identify new arsenic targets and allow research on protein/arsenic complexes. In this work, we analyzed the performance of the fluorescent compound APAO-FITC (synthesized from p-aminophenylarsenoxide, APAO, and fluorescein isothiocyanate, FITC) in arsenic/protein binding assays using thioredoxin 1 (Trx) as an arsenic-binding protein model. The Trx-APAO-FITC complex was studied through different spectroscopic techniques involving UV-Vis, fluorescence, atomic absorption, infrared and circular dichroism. Our results show that APAO-FITC binds efficiently and specifically to the Trx binding site, labeling the protein fluorescently, without altering its structure and activity. In summary, we were able to study a protein/arsenic complex model, using APAO-FITC as a labeling probe. The use of APAO-FITC in the identification of different protein and cell targets, as well as in in vivo biodistribution studies, conformational studies of arsenic-binding proteins, and studies for the design of drug delivery systems for arsenic anti-cancer therapies, is highly promising.

  6. A spectroscopic study of the impact of arsenic speciation on arsenic/phosphorous uptake and plant growth in tumbleweed (Salsola kali)

    PubMed Central

    de la Rosa, Guadalupe; Parsons, Jason G.; Martinez-Martinez, Alejandro; Peralta-Videa, Jose R.; Gardea-Torresdey, Jorge L.

    2008-01-01

    This manuscript reports the toxic effects of As2O3 (arsenic trioxide) and As2O5 (arsenic pentoxide) on S. kali, as well as the arsenic and phosphate uptake, and arsenic coordination within plant tissues. Plants were germinated and grown for 15 days on a Hoagland modified medium containing either As(III) (arsenic trioxide) or As(V) (arsenic pentoxide). Subsequently, the seedlings were measured and analyzed using ICP-OES and XAS techniques. Plants stressed with 2 mg L−1 of whichever As(III) or As(V) concentrated 245 ± 19, 30 ± 1, and 60 ± 3 mg As kg−1 d. wt, or 70 ± 6, 10 ± 0.3, and 27 ± 3 mg As kg−1 d. wt in roots, stems, and leaves, respectively. Arsenate was less toxic and more As translocation occurred from the roots to the leaves. All treatments reduced P concentration at root level; however, only As(V) at 2 and 4 mg L−1 reduced P concentration at leaf level. Regardless the arsenic species supplied to the plants, arsenic was found in plant tissues as As(III) coordinated to three sulfur ligands with an interatomic distance of approximately 2.25 Å. PMID:16570626

  7. Anticancer chemotherapy

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Despite troubled beginnings, anticancer chemotherapy has made significant contribution to the control of cancer in man, particularly within the last two decades. Early conceptual observations awakened the scientific community to the potentials of cancer chemotherapy. There are now more than 50 agents that are active in causing regression of clinical cancer. Chemotherapy's major conceptual contributions are two-fold. First, there is now proof that patients with overt metastatic disease can be cured, and second, to provide a strategy for control of occult metastases. In man, chemotherapy has resulted in normal life expectancy for some patients who have several types of metastatic cancers, including choriocarcinoma, Burkitt's lymphomas, Wilm's tumor, acute lymphocytic leukemia, Hodgkins disease, diffuse histiocytic lymphoma and others. Anticancer chemotherapy in Veterinary medicine has evolved from the use of single agents, which produce only limited remissions, to the concept of combination chemotherapy. Three basic principles underline the design of combination chemotherapy protocols; the fraction of tumor cell killed by one drug is independent of the fraction killed by another drug; drugs with different mechanisms of action should be chosen so that the antitumor effects will be additive; and since different classes of drugs have different toxicities the toxic effects will not be additive.

  8. The environmental fate of arsenic in surface soil contaminated by historical herbicide application.

    PubMed

    Qi, Yongqiang; Donahoe, Rona J

    2008-11-01

    Soils from many industrial sites are contaminated with arsenic because of the historical application of herbicide containing arsenic trioxide. The strong affinity of aqueous arsenic species for soil components has led to the retention of significant amounts of arsenic in surface soils decades after the original source application. Soil collected from a site which received a one-time surficial application of arsenical herbicide in the 1950s was investigated to understand the fate of arsenic under natural leaching conditions. Sequential chemical extraction of the contaminated soil revealed that the majority of the arsenic is in its secondary form. The synthetic acid rain leaching of arsenic from the weathered soil can be divided into two distinct stages. During the first stage, the leachate arsenic concentration underwent a rapid decline which suggests an equilibrium-controlled release event. The second leaching stage was marked by a slow, steady release of arsenic, a signature of a kinetically controlled process. A mathematical approach was employed to identify and describe the two distinct arsenic releasing processes (equilibrium desorption and kinetic desorption). This model considers both desorption processes simultaneously and produces leachate arsenic concentrations in good agreement with the measured data. According to the modeling results, 20% of the arsenic remaining in the soil resides in the herbicide source material after five decades of natural leaching; 25% exists on reversible adsorption sites and 55% is present on irreversible adsorption sites.

  9. 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...

  10. Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic.

    PubMed

    Zhang, Hai-Nan; Yang, Lina; Ling, Jian-Ya; Czajkowsky, Daniel M; Wang, Jing-Fang; Zhang, Xiao-Wei; Zhou, Yi-Ming; Ge, Feng; Yang, Ming-Kun; Xiong, Qian; Guo, Shu-Juan; Le, Huang-Ying; Wu, Song-Fang; Yan, Wei; Liu, Bingya; Zhu, Heng; Chen, Zhu; Tao, Sheng-Ce

    2015-12-01

    Arsenic is highly effective for treating acute promyelocytic leukemia (APL) and has shown significant promise against many other tumors. However, although its mechanistic effects in APL are established, its broader anticancer mode of action is not understood. In this study, using a human proteome microarray, we identified 360 proteins that specifically bind arsenic. Among the most highly enriched proteins in this set are those in the glycolysis pathway, including the rate-limiting enzyme in glycolysis, hexokinase-1. Detailed biochemical and metabolomics analyses of the highly homologous hexokinase-2 (HK2), which is overexpressed in many cancers, revealed significant inhibition by arsenic. Furthermore, overexpression of HK2 rescued cells from arsenic-induced apoptosis. Our results thus strongly implicate glycolysis, and HK2 in particular, as a key target of arsenic. Moreover, the arsenic-binding proteins identified in this work are expected to serve as a valuable resource for the development of synergistic antitumor therapeutic strategies.

  11. Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic

    PubMed Central

    Zhang, Hai-nan; Yang, Lina; Ling, Jian-ya; Czajkowsky, Daniel M.; Wang, Jing-Fang; Zhang, Xiao-Wei; Zhou, Yi-Ming; Ge, Feng; Yang, Ming-kun; Xiong, Qian; Guo, Shu-Juan; Le, Huang-Ying; Wu, Song-Fang; Yan, Wei; Liu, Bingya; Zhu, Heng; Chen, Zhu; Tao, Sheng-ce

    2015-01-01

    Arsenic is highly effective for treating acute promyelocytic leukemia (APL) and has shown significant promise against many other tumors. However, although its mechanistic effects in APL are established, its broader anticancer mode of action is not understood. In this study, using a human proteome microarray, we identified 360 proteins that specifically bind arsenic. Among the most highly enriched proteins in this set are those in the glycolysis pathway, including the rate-limiting enzyme in glycolysis, hexokinase-1. Detailed biochemical and metabolomics analyses of the highly homologous hexokinase-2 (HK2), which is overexpressed in many cancers, revealed significant inhibition by arsenic. Furthermore, overexpression of HK2 rescued cells from arsenic-induced apoptosis. Our results thus strongly implicate glycolysis, and HK2 in particular, as a key target of arsenic. Moreover, the arsenic-binding proteins identified in this work are expected to serve as a valuable resource for the development of synergistic antitumor therapeutic strategies. PMID:26598702

  12. Serum acetyl cholinesterase as a biomarker of arsenic induced neurotoxicity in sprague-dawley rats.

    PubMed

    Patlolla, Anita K; Tchounwou, Paul B

    2005-04-01

    Arsenic is an environmental toxicant, and one of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which may cause severe injury/damage to the nervous system. The main objective of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of acetyl cholinesterase; a critical important nervous system enzyme that hydrolyzes the neurotransmitter acetylcholine. Four groups of six male rats each weighing an average 60 +/- 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW), one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthesia, blood specimens were immediately collected using heparinized syringes, and acetyl cholinesterase detection and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly decreased the activity of cholinesterase in the Sprague-Dawley rats. Acetyl cholinesterase activities of 6895 +/- 822, 5697 +/- 468, 5069 +/- 624, 4054 +/- 980, and 3158 +/- 648 U/L were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual decrease in acetyl cholinesterase activity with increasing doses of arsenic. These findings indicate that acetyl

  13. Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells.

    PubMed

    Ge, Feng; Lu, Xin-Peng; Zeng, Hui-Lan; He, Quan-Yuan; Xiong, Sheng; Jin, Lin; He, Qing-Yu

    2009-06-01

    Multiple myeloma (MM) is an incurable plasma cell malignancy with a terminal phase marked by increased proliferation and resistance to therapy. Arsenic trioxide (ATO), an antitumor agent with a multifaceted mechanism of action, displayed clinical activity in patients with late-stage multiple myeloma. However, the precise mechanism(s) of action of ATO has not been completely elucidated. In the present study, we used proteomics to analyze the ATO-induced protein alterations in MM cell line U266 and then investigated the molecular pathways responsible for the anticancer actions of ATO. Several clusters of proteins altered in expression in U266 cells upon ATO treatment were identified, including down-regulated signal transduction proteins and ubiquitin/proteasome members, and up-regulated immunity and defense proteins. Significantly regulated 14-3-3zeta and heat shock proteins (HSPs) were selected for further functional studies. Overexpression of 14-3-3zeta in MM cells attenuated ATO-induced cell death, whereas RNAi-based 14-3-3zeta knock-down or the inhibition of HSP90 enhanced tumor cell sensitivity to the ATO induction. These observations implicate 14-3-3zeta and HSP90 as potential molecular targets for drug intervention of multiple myeloma and thus improve our understanding on the mechanisms of antitumor activity of ATO.

  14. 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. PMID:9347899

  15. 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.

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

    PubMed Central

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

    1997-01-01

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

  17. Organic transformations catalyzed by methylrhenium trioxide

    SciTech Connect

    Zhu, Z.

    1995-11-01

    Methylrhenium trioxide (MTO), CH{sub 3}ReO{sub 3}, was first prepared in 1979. MTO forms stable or unstable adducts with electron-rich ligands, such as amines (quinuclidine, 1,4-diazabicyclo-octane, pyridine, aniline, 2,2{prime}-bipyridine), alkynes, olefins, 1,2-diols, catechols, hydrogen peroxide, water, thiophenols, 1,2-dithiols, triphenylphosphine, 2-aminophenols, 2-aminothiophenols, 8-hydroxyquinoline and halides (Cl-, Br-, I-). After coordination, different further reactions will occur for different reagents. Reactions described in this report include the dehydration of alcohols, direct amination of alcohols, activation of hydrogen peroxide, oxygen transfer, and decomposition of ethyl diazoacetate.

  18. An Aerosol Condensation Model for Sulfur Trioxide

    SciTech Connect

    Grant, K E

    2008-02-07

    This document describes a model for condensation of sulfuric acid aerosol given an initial concentration and/or source of gaseous sulfur trioxide (e.g. fuming from oleum). The model includes the thermochemical effects on aerosol condensation and air parcel buoyancy. Condensation is assumed to occur heterogeneously onto a preexisting background aerosol distribution. The model development is both a revisiting of research initially presented at the Fall 2001 American Geophysical Union Meeting [1] and a further extension to provide new capabilities for current atmospheric dispersion modeling efforts [2]. Sulfuric acid is one of the most widely used of all industrial chemicals. In 1992, world consumption of sulfuric acid was 145 million metric tons, with 42.4 Mt (mega-tons) consumed in the United States [10]. In 2001, of 37.5 Mt consumed in the U.S., 74% went into producing phosphate fertilizers [11]. Another significant use is in mining industries. Lawuyi and Fingas [7] estimate that, in 1996, 68% of use was for fertilizers and 5.8% was for mining. They note that H{sub 2}SO{sub 4} use has been and should continue to be very stable. In the United States, the elimination of MTBE (methyl tertiary-butyl ether) and the use of ethanol for gasoline production are further increasing the demand for petroleum alkylate. Alkylate producers have a choice of either a hydrofluoric acid or sulfuric acid process. Both processes are widely used today. Concerns, however, over the safety or potential regulation of hydrofluoric acid are likely to result in most of the growth being for the sulfuric acid process, further increasing demand [11]. The implication of sulfuric acid being a pervasive industrial chemical is that transport is also pervasive. Often, this is in the form of oleum tankers, having around 30% free sulfur trioxide. Although sulfuric acid itself is not a volatile substance, fuming sulfuric acid (referred to as oleum) is [7], the volatile product being sulfur trioxide

  19. Arsenic poisoning.

    PubMed

    Schoolmeester, W L; White, D R

    1980-02-01

    Arsenic poisoning continues to require awareness of its diverse clinical manifestations. Industry is the major source of arsenic exposure. Although epidemiologic studies strongly contend that arsenic is carcinogenic, there are little supportive research data. Arsenic poisoning, both acute and chronic, is often overlooked initially in the evaluation of the patient with multisystem disease, but once it is suspected, many accurate methods are available to quantitate the amount and duration of exposure. Treatment with dimercaprol remains the mainstay of therapy, and early treatment is necessary to prevent irreversible complications.

  20. Mineral trioxide aggregate apexification: A novel approach

    PubMed Central

    Purra, Aamir Rashid; Ahangar, Fayaz Ahmed; Chadgal, Sachin; Farooq, Riyaz

    2016-01-01

    The treatment of choice for necrotic teeth with immature root is apexification, which is induction of apical closure to produce more favorable conditions for conventional root canal filling. The most commonly advocated medicament is calcium hydroxide although recently considerable interest has been expressed in the use of mineral trioxide aggregate (MTA). MTA offers the option of a two-visit apexification procedure so that the fragile tooth can be restored immediately. However, difficulty in placing the material in the wide apical area requires the use of an apical matrix. Materials such as collagen, calcium sulfate, and hydroxyapatite have been used for this purpose. This article describes the use of resorbable suture material to form the apical matrix which offers many advantages over the contemporary materials. PMID:27563191

  1. Mineral trioxide aggregate apexification: A novel approach.

    PubMed

    Purra, Aamir Rashid; Ahangar, Fayaz Ahmed; Chadgal, Sachin; Farooq, Riyaz

    2016-01-01

    The treatment of choice for necrotic teeth with immature root is apexification, which is induction of apical closure to produce more favorable conditions for conventional root canal filling. The most commonly advocated medicament is calcium hydroxide although recently considerable interest has been expressed in the use of mineral trioxide aggregate (MTA). MTA offers the option of a two-visit apexification procedure so that the fragile tooth can be restored immediately. However, difficulty in placing the material in the wide apical area requires the use of an apical matrix. Materials such as collagen, calcium sulfate, and hydroxyapatite have been used for this purpose. This article describes the use of resorbable suture material to form the apical matrix which offers many advantages over the contemporary materials. PMID:27563191

  2. The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: Moving toward an effective oral, outpatient therapy.

    PubMed

    Falchi, Lorenzo; Verstovsek, Srdan; Ravandi-Kashani, Farhad; Kantarjian, Hagop M

    2016-04-15

    The therapeutic potential of arsenic derivatives has long been recognized and was recently rediscovered in modern literature. Early studies demonstrated impressive activity of this compound in patients with relapsed acute promyelocytic leukemia (APL). Over the last 2 decades, intravenous arsenic trioxide has been used successfully, both alone and in combination with other agents, for the treatment of APL and, with some success, of other myeloid neoplasms. Arsenic trioxide is currently part the standard of care for patients with APL. More recently, oral formulations of this compound have been developed and are entering clinical practice. In this review, the authors discuss the evolution of arsenic in the treatment of APL and other myeloid neoplasms. PMID:26716387

  3. Evaluation of DNA damage in patients with arsenic poisoning: urinary 8-hydroxydeoxyguanine.

    PubMed

    Yamauchi, Hiroshi; Aminaka, Yoshito; Yoshida, Katsumi; Sun, Guifan; Pi, Jingbo; Waalkes, Michael P

    2004-08-01

    The relationship between arsenic exposure and DNA damage in patients with acute or chronic arsenic poisoning was analyzed. Urinary 8-hydroxydeoxyguanine (8-OHdG) concentrations were measured as an indication of oxidative DNA damage. A remarkable increase in 8-OHdG in the urine was observed in 60% of 52 patients with acute arsenic poisoning from the accidental oral intake of the arsenic trioxide. This was two- to threefold higher than levels in normal healthy subjects (n = 248). There was a clear relationship between arsenic concentrations in urine after acute poisoning and elevated levels of 8-OHdG. Levels of urinary 8-OHdG returned to normal within 180 days after the acute arsenic poisoning event. In patients chronically poisoned by the consumption of well water with elevated levels of arsenate [As(V)], elevated 8-OHdG concentrations in urine were also observed. A significant correlation between the 8-OHdG levels and arsenic levels in the urine was observed in 82 patients with chronic poisoning. Thus, evidence of oxidative DNA damage occurred in acute arsenic poisoning by arsenite [As(III)] and in chronic arsenic poisoning by As(V). In chronic poisoning patients provided low-arsenic drinking water, evidence of DNA damage subsided between 9 months and 1 year after the high levels of arsenic intake were reduced. The initial level of arsenic exposure appeared to dictate the length of this recovery period. These data indicate that some aspects of chronic and acute arsenic poisoning may be reversible with the cessation of exposure. This knowledge may contribute to our understanding of the risk elevation from arsenic carcinogenesis and perhaps be used in a prospective fashion to assess individual risk.

  4. Understanding the Oxygen Vacancy in Tungsten Trioxide

    NASA Astrophysics Data System (ADS)

    Wang, Wennie; Janotti, Anderson; van de Walle, Chris G.

    2015-03-01

    Tungsten trioxide (WO3) has a variety of applications in gas sensors, photocatalysis, and smart windows. As an electrochromic BO3 perovskite, WO3 turns from transparent to blue upon doping. This color change is correlated with a drop in transmittance of near-IR radiation, and is used in smart windows for energy efficiency. In addition to monovalent species doping that modulates optical properties, oxygen deficiencies have been found to have a similar electrochromic effect. The influence of oxygen vacancies on electronic structure and how it corresponds to electrochromic behavior remains a topic of debate. In this work, we examine the oxygen vacancy in monoclinic WO3 and its influence on electronic structure using density functional theory with a hybrid functional. We investigate the relative stability of different charge states and its implications for electrical properties, such as conductivity and electrochromism. We find oxygen vacancies to be shallow donors, and explore similarities and differences with monovalent species doping. Finally, we compare our theoretical findings with experiment to elucidate how vacancies may contribute to electrochromic behavior. This work is supported by DOE and NSF.

  5. Rapid Reduction in Breast Cancer Mortality With Inorganic Arsenic in Drinking Water

    PubMed Central

    Smith, Allan H.; Marshall, Guillermo; Yuan, Yan; Steinmaus, Craig; Liaw, Jane; Smith, Martyn T.; Wood, Lily; Heirich, Marissa; Fritzemeier, Rebecca M.; Pegram, Mark D.; Ferreccio, Catterina

    2014-01-01

    Background Arsenic trioxide is effective in treating promyelocytic leukemia, and laboratory studies demonstrate that arsenic trioxide causes apoptosis of human breast cancer cells. Region II in northern Chile experienced very high concentrations of inorganic arsenic in drinking water, especially in the main city Antofagasta from 1958 until an arsenic removal plant was installed in 1970. Methods We investigated breast cancer mortality from 1950 to 2010 among women in Region II compared to Region V, which had low arsenic water concentrations. We conducted studies on human breast cancer cell lines and compared arsenic exposure in Antofagasta with concentrations inducing apoptosis in laboratory studies. Findings Before 1958, breast cancer mortality rates were similar, but in 1958–1970 the rates in Region II were half those in Region V (rate ratio RR = 0.51, 95% CI 0.40–0.66; p < 0.0001). Women under the age of 60 experienced a 70% reduction in breast cancer mortality during 1965–1970 (RR = 0.30, 0.17–0.54; p < 0.0001). Breast cancer cell culture studies showed apoptosis at arsenic concentrations close to those estimated to have occurred in people in Region II. Interpretation We found biologically plausible major reductions in breast cancer mortality during high exposure to inorganic arsenic in drinking water which could not be attributed to bias or confounding. We recommend clinical trial assessment of inorganic arsenic in the treatment of advanced breast cancer. PMID:25580451

  6. Acute arsenic exposure treated with oral D-penicillamine

    SciTech Connect

    Watson, W.A.; Veltri, J.C.; Metcalf, T.J.

    1981-06-01

    Arsenic trioxide (As2O3) is the arsenic compound most commonly implicated in acute toxic exposures. The toxicity of As2O3 is a function of the preparation's particle size and solubility. A 16-month-old female presented at a local emergency room with a history of acute ingestion of As2O3 obtained from a commonly available pesticide. Classic gastrointestinal symptoms of arsenic toxicity were exhibited shortly after ingestion; however, aggressive decontamination followed by early chelation therapy resulted in the cessation of toxic manifestations and an uneventful recovery. Oral chelation therapy with D-penicillamine has rarely been reported as an effective agent in the treatment of arsenic poisoning. The case reported herein is further documentation that D-penicillamine is effective in increasing the mobilization of arsenic. The authors also recommend that products containing arsenic compounds should not be used where children may come in contact with them until the Environmental Protection Agency's child resistant packaging regulations become effective.

  7. Total and Inorganic Arsenic in Mid-Atlantic Marine Fish and Shellfish and Implications for Fish Advisories

    SciTech Connect

    Greene, Richard; Crecelius, Eric A.

    2006-02-06

    Up to 33.3 metric tons of arsenic trioxide were spilled off the Middle Atlantic coast of the United States in January of 1992 during a shipping accident. Historical fish tissue data for samples collected in the Delaware Inland Bays before and after the spill reveal a prominent spike in total arsenic in summer flounder following the spill and a gradual decline ever since. In 2002, a small study was conducted to determine whether summer flounder migrating into the Delaware Inland Bays from the Continental Shelf in the spring contain higher body burdens of arsenic than summer flounder migrating out of the Inland Bays in the fall. Total arsenic was significantly higher in the incoming fish. Considering that summer flounder overwinter at the spill site, that arsenic trioxide is a dense powder of limited solubility that would tend to incorporate into the sediments, and that summer flounder are demersal fish, we conclude that summer flounder accumulate arsenic offshore and that the likely source of their extra body burden is the spilled arsenic. Speciation of arsenic in the summer flounder, as well as in Atlantic croaker, striped bass, and hard clam reveal low concentrations (0.5 ? 20 ug/kg ww) of toxic inorganic arsenic. DMA was more than an order of magnitude greater in hard clam meats than in the other species tested, a finding attributed to arsenic uptake by phytoplankton and subsequent dietary uptake by the clam. Risk assessment using the inorganic arsenic concentrations was used to conclude that a fish advisory is not warranted.

  8. Effects of Arsenic on Osteoblast Differentiation in Vitro and on Bone Mineral Density and Microstructure in Rats

    PubMed Central

    Wu, Cheng-Tien; Lu, Tung-Ying; Chan, Ding-Cheng; Tsai, Keh-Sung; Yang, Rong-Sen

    2014-01-01

    Background: Arsenic is a ubiquitous toxic element and is known to contaminate drinking water in many countries. Several epidemiological studies have shown that arsenic exposure augments the risk of bone disorders. However, the detailed effect and mechanism of inorganic arsenic on osteoblast differentiation of bone marrow stromal cells and bone loss still remain unclear. Objectives: We investigated the effects and mechanism of arsenic on osteoblast differentiation in vitro and evaluated bone mineral density (BMD) and bone microstructure in rats at doses relevant to human exposure from drinking water. Methods: We used a cell model of rat primary bone marrow stromal cells (BMSCs) and a rat model of long-term exposure with arsenic-contaminated drinking water, and determined bone microstructure and BMD in rats by microcomputed tomography (μCT). Results: We observed significant attenuation of osteoblast differentiation after exposure of BMSCs to arsenic trioxide (0.5 or 1 μM). After arsenic treatment during differentiation, expression of runt-related transcription factor-2 (Runx2), bone morphogenetic protein-2 (BMP-2), and osteocalcin in BMSCs was inhibited and phosphorylation of enhanced extracellular signal-regulated kinase (ERK) was increased. These altered differentiation-related molecules could be reversed by the ERK inhibitor PD98059. Exposure of rats to arsenic trioxide (0.05 or 0.5 ppm) in drinking water for 12 weeks altered BMD and microstructure, decreased Runx2 expression, and increased ERK phosphorylation in bones. In BMSCs isolated from arsenic-treated rats, osteoblast differentiation was inhibited. Conclusions: Our results suggest that arsenic is capable of inhibiting osteoblast differentiation of BMSCs via an ERK-dependent signaling pathway and thus increasing bone loss. Citation: Wu CT, Lu TY, Chan DC, Tsai KS, Yang RS, Liu SH. 2014. Effects of arsenic on osteoblast differentiation in vitro and on bone mineral density and microstructure in rats. Environ

  9. Lutein Has a Protective Effect on Hepatotoxicity Induced by Arsenic via Nrf2 Signaling

    PubMed Central

    Li, Shugang; Ding, Yusong; Niu, Qiang; Xu, Shangzhi; Pang, Lijuan; Ma, Rulin; Jing, Mingxia; Feng, Gangling; Tang, Jing Xia; Zhang, Qian; Ma, Xiaomei; Yan, Yizhong; Wang, Hai Xia; Li, Feng; Guo, Shuxia

    2015-01-01

    Arsenic produces liver disease through the oxidative stress. While lutein can alleviate cytotoxic and oxidative injury, nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a critical role in defending oxidative species. However, the mechanisms by which lutein protects the liver against the effect of arsenic are not known. Therefore, this study aims to investigate the mechanisms involved in the action of lutein using mice model in which hepatotoxicity was induced by arsenic. We found that mice treatment with lutein could reverse changes in morphological and liver indexes and result in a significant improvement in hepatic function comparing with arsenic trioxide group. Lutein treatment improved the activities of antioxidant enzymes and attenuated increasing of ROS and MDA induced by arsenic trioxide. Lutein could increase the mRNA and protein expression of Nrf2 signaling related genes (Nrf2, Nqo1, Ho-1, and Gst). These findings provide additional evidence that lutein may be useful for reducing reproductive injury associated with oxidative stress by the activation of Nrf2 signaling. Our findings suggest a possible mechanism of antioxidant lutein in preventing the hepatotoxicity, which implicate that a dietary lutein may be a potential treatment for liver diseases, especially for arsenicosis therapy. PMID:25815309

  10. Lutein has a protective effect on hepatotoxicity induced by arsenic via Nrf2 signaling.

    PubMed

    Li, Shugang; Ding, Yusong; Niu, Qiang; Xu, Shangzhi; Pang, Lijuan; Ma, Rulin; Jing, Mingxia; Feng, Gangling; Tang, Jing Xia; Zhang, Qian; Ma, Xiaomei; Yan, Yizhong; Zhang, Jingyu; Wei, Meng; Wang, Hai Xia; Li, Feng; Guo, Shuxia

    2015-01-01

    Arsenic produces liver disease through the oxidative stress. While lutein can alleviate cytotoxic and oxidative injury, nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a critical role in defending oxidative species. However, the mechanisms by which lutein protects the liver against the effect of arsenic are not known. Therefore, this study aims to investigate the mechanisms involved in the action of lutein using mice model in which hepatotoxicity was induced by arsenic. We found that mice treatment with lutein could reverse changes in morphological and liver indexes and result in a significant improvement in hepatic function comparing with arsenic trioxide group. Lutein treatment improved the activities of antioxidant enzymes and attenuated increasing of ROS and MDA induced by arsenic trioxide. Lutein could increase the mRNA and protein expression of Nrf2 signaling related genes (Nrf2, Nqo1, Ho-1, and Gst). These findings provide additional evidence that lutein may be useful for reducing reproductive injury associated with oxidative stress by the activation of Nrf2 signaling. Our findings suggest a possible mechanism of antioxidant lutein in preventing the hepatotoxicity, which implicate that a dietary lutein may be a potential treatment for liver diseases, especially for arsenicosis therapy.

  11. [Early onset of torsades de Pointes and elevated levels of serum troponin I due to acute arsenic poisoning].

    PubMed

    Ortega Carnicer, J; Ruiz Lorenzo, F; Mañas García, D; Ceres Alabau, F

    2006-03-01

    Most cases of acute arsenic poisoning occur through accidental or voluntary ingestion of pesticides or insecticides, and all body systems are affected. Arsenic can prolong the QT interval and lead to torsades of Pointes, a crucial type of arrhythmia characteristic of such QT interval prolongation. In our revision of the literature, there have been found only 5 cases of torsades of Pointes due to acute arsenic poisoning. Recently, there have been published four additional cases in patients with refractory or recurrent acute promyelocytic leukemia being treated with arsenic trioxide. In all nine cases, torsades of pointes appeared slowly after poisoning. Herein is described a case of acute arsenic poisoning which led to an early onset of torsades of Pointes, hypopotasemia and high levels of serum troponin I.

  12. Effect of iron redox transformations on arsenic solid-phase associations in an arsenic-rich, ferruginous hydrothermal sediment

    NASA Astrophysics Data System (ADS)

    Handley, Kim M.; McBeth, Joyce M.; Charnock, John M.; Vaughan, David J.; Wincott, Paul L.; Polya, David A.; Lloyd, Jonathan R.

    2013-02-01

    Well-constrained laboratory incubations of a ferruginous marine hydrothermal sediment from Santorini, Greece, were used to elucidate the effect of microbially induced redox transformations on arsenic speciation and mobility. Despite naturally high arsenic concentrations (˜400 mg/kg), the sediment has a low As:Fe ratio (1:1000 wt/wt). Acetate-amendment of sediment, extracted from the naturally-occurring suboxic-anoxic (Eh -60 to -138 mV) transition zone, promoted Fe(III) reduction, and increased the concentration of Fe(II) from ˜40% to ˜60% in the bulk sediment. Sulfate, which was present at lower concentrations, was also reduced. Phylogenetic 16S rRNA and dsr gene analysis suggested that Fe(III) and sulfate were reduced by bacteria related to Malonomonas rubra and Desulfosarcina variabilis, respectively. Arsenic remained predominantly as arsenic trioxide (As2O3) throughout the amendment experiment. However, the percentage of total arsenic present within poorly-crystalline iron oxides decreased from ˜69% to ˜32%, while the percentage incorporated within crystalline iron-containing minerals or sorbed to surfaces via inner-sphere complexes increased significantly (to 22% and 30%, respectively). Re-oxidation of the system with nitrate resulted in incomplete reduction of the nitrate pool, and partial re-association of arsenic with the poorly-crystalline iron fraction. Exposure to air led to virtually complete reversal of the arsenic partitioning, and oxidation of 71% As(III) to As(V). During aeration, oxidation of sediment-bound sulfur/sulfide occurred, alongside an observed ˜63% decrease in arsenic bound to this minor component. Analogous trends in arsenic-sediment associations were observed in the natural, unamended sediment depth-profile, whereby a greater proportion of arsenic (34% As(III), 66% As(V)) was bound within poorly-crystalline iron oxides at the sediment-water interface. Arsenic (96% As(III)) was increasingly incorporated within well

  13. Multiple organ failure with the adult respiratory distress syndrome in homicidal arsenic poisoning.

    PubMed

    Bolliger, C T; van Zijl, P; Louw, J A

    1992-01-01

    A 30-year-old man and a 39-year-old woman, who was 28 weeks pregnant, were simultaneously poisoned by eating chocolate containing arsenic trioxide. They developed a picture of multiple organ failure peaking around the 8th to 10th day after ingestion, with the development of life-threatening adult respiratory distress syndrome (ARDS) in both patients. This rarely reported complication of arsenic poisoning was managed successfully by intubation and mechanical ventilation with positive end expiratory pressure in both patients. Hemodynamic and laboratory data are presented supporting the clinical course. Arsenic toxicity further resulted in intrauterine fetal death. The effects of severe arsenic poisoning leading to early multiple organ failure with ARDS as well as to protracted, debilitating polyneuropathy are discussed.

  14. Study of the effect of inorganic and organic complexes of arsenic metal on the status of GSH in T. cells and B. cells of blood.

    PubMed

    Ullah, Naseem; Khan, Muhammad Farid; Jan, Syed Umer; Mukhtiar, Muhammad; Khan, Haroon; Rehman, Asim-ur

    2015-03-01

    Arsenic is a major threat to large part of the population due to its carcinogenic nature. The toxicity of Arsenic varies with its chemical form and oxidation states. Glutathione (GSH), a major intra-cellular tripeptide plays a major role in arsenic detoxification. The present study was designed to provide insight into the extent of changes in GSH level by inorganic arsenic in the form of Arsenic trioxide (ATO) and organic arsenic in the form of nitro benzene arsenic acid (NBA). Lymphocytes (T.cells and B.cells) were investigated for determination of change in GSH metabolic status caused by arsenic. The depletion of GSH level positively correlated with increasing arsenic concentration and time of incubation. The decline in GSH level was consistent with increasing pH and physiological temperature. Our findings show that changes in GSH status produced by Arsenic could be due to adduct (As-(SG)3) formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of inorganic and organic arsenicals. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity.

  15. Study of the effect of inorganic and organic complexes of arsenic metal on the status of GSH in T. cells and B. cells of blood.

    PubMed

    Ullah, Naseem; Khan, Muhammad Farid; Jan, Syed Umer; Mukhtiar, Muhammad; Khan, Haroon; Rehman, Asim-ur

    2015-03-01

    Arsenic is a major threat to large part of the population due to its carcinogenic nature. The toxicity of Arsenic varies with its chemical form and oxidation states. Glutathione (GSH), a major intra-cellular tripeptide plays a major role in arsenic detoxification. The present study was designed to provide insight into the extent of changes in GSH level by inorganic arsenic in the form of Arsenic trioxide (ATO) and organic arsenic in the form of nitro benzene arsenic acid (NBA). Lymphocytes (T.cells and B.cells) were investigated for determination of change in GSH metabolic status caused by arsenic. The depletion of GSH level positively correlated with increasing arsenic concentration and time of incubation. The decline in GSH level was consistent with increasing pH and physiological temperature. Our findings show that changes in GSH status produced by Arsenic could be due to adduct (As-(SG)3) formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of inorganic and organic arsenicals. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity. PMID:25730780

  16. EMISSIONS OF SULFUR TRIOXIDE FROM COAL-FIRED POWER PLANTS

    EPA Science Inventory

    Emissions of sulfur trioxide (SO3) are a key component of plume opacity and acid deposition. Consequently, these emissions need to be low enough not to cause opacity violations and acid deposition. Generally, a small fraction of sulfur in coal is converted to SO3 in coal-fired co...

  17. Arsenic and its combinations in cancer therapeutics.

    PubMed

    Prajapati, Vandana; Kale, Raosaheb K; Singh, Rana P

    2011-06-01

    Arsenic is a metalloid that is considered to be a paradox in terms of its role both as a carcinogen and as a therapeutic agent. Chronic exposure to arsenic in drinking water has been linked with the development of various pathological conditions including cancer. Nevertheless, the therapeutic potential of arsenic and its derivatives in a variety of diseases have been exploited in the past. However, its role and mechanism of action as a therapeutic agent still remain an active area of research and investigation. Our ongoing work also suggests varied responses in cancer cells exposed to lower versus higher concentrations of arsenic. Furthermore, the arsenic combinations with chemopreventive or anticancer agents have been observed to sensitize the cell for cell-cycle arrest and cell death. Here, we have provided the account of recent updates on the mechanism of action of arsenic and its derivatives that lead to various disorders, and its role as a therapeutic agent both as a single agent as well as in combination chemotherapy. PMID:22822509

  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. Construction of carbon nanodots/tungsten trioxide and their visible-light sensitive photocatalytic activity.

    PubMed

    Yan, Fanyong; Kong, Depeng; Fu, Yang; Ye, Qianghua; Wang, Yinyin; Chen, Li

    2016-03-15

    Herein we designed a simple and effective method for synthesizing carbon nanodots/tungsten trioxide nanocomposite with high photocatalytic activity. The as-prepared carbon nanodots/ tungsten trioxide has strong photoabsorption under visible light irradiation. Then, carbon nanodots/tungsten trioxide was successfully applied to the degradation of methylene blue. The photodegradation efficiency of methylene blue can be reached as high as 100% after 0.5 h visible light illumination. In addition, carbon nanodots/tungsten trioxide could also be used to degrade rhodamine B and methyl orange. Most importantly, the photocatalytic activity of carbon nanodots/tungsten trioxide did not exhibit obvious changes after five cycles. The results indicate that carbon nanodots/tungsten trioxide has potential applications in the degradation of organic pollutants in industrial waste water.

  20. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    PubMed

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  1. Protective effect of naringenin on hepatic and renal dysfunction and oxidative stress in arsenic intoxicated rats.

    PubMed

    Mershiba, Sam Daniel; Dassprakash, M Velayutham; Saraswathy, Sundara Dhakshinamurthy

    2013-05-01

    Arsenic has a long history as a potent human poison, chronic exposure over a period of time may result in the manifestation of toxicity in practically all systems of the body. In the present investigation the efficacy of naringenin (NRG), a naturally occurring citrus flavanone against arsenic-induced hepatotoxic and nephrotoxic manifestations have been studied in rats. Arsenic trioxide was administered orally at the dose of 2 mg/kg/day with or without combination of NRG (20 or 50 mg/kg/day) for 28 days. At the end of the experimental period the hepatic and renal dysfunction was evaluated by histological examination, serum biomarkers and markers of oxidative stress; lipid peroxidation (LPO), reduced glutathione (GSH) and antioxidant enzymes. Arsenic intoxication increased serum bilirubin, urea, uric acid and creatinine levels, additionally enhanced the activities of hepatic marker enzymes aspartate transaminase, alanine transaminase and alkaline phosphatase. Also, the hepatic and renal tissues showed a marked elevation in LPO levels with a decrease in GSH content and the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase on arsenic treatment. Simultaneous treatment with NRG restored the activities of serum biomarkers and antioxidant enzymes in the tissues in a dose-dependent manner. Furthermore, the histopathological studies confirmed the protective effect of NRG co-treatment by reducing the pathological changes due to arsenic intoxication in both liver and kidney. Thus, our present study demonstrates that NRG has a potential to protect arsenic-induced oxidative hepatic and renal dysfunction.

  2. Arsenite as the probable active species in the human carcinogenicity of arsenic: mouse micronucleus assays on Na and K arsenite, orpiment, and Fowler's solution.

    PubMed Central

    Tinwell, H; Stephens, S C; Ashby, J

    1991-01-01

    Sodium arsenite, potassium arsenite, and Fowler's solution (arsenic trioxide dissolved in potassium bicarbonate) are equally active in the mouse bone marrow micronucleus assay (approximately 10 mg/kg by IP injection). The natural ore orpiment (principally As2S3) was inactive despite blood levels of arsenic of 300 to 900 ng/mL in treated mice at 24 hr. Sodium arsenite was active in three strains of mice. It is suggested that the human lung cancer observed among arsenic ore smelters and the skin cancer among people exposed therapeutically to Fowler's solution, have, as their common origin, the genotoxic arsenite ion AsO2-. The difficulty experienced when attempting to demonstrate rodent carcinogenicity for derivatives of arsenic suggests that the bone marrow micronucleus assay may act as a useful assay for potentially carcinogenic arsenic derivatives. PMID:1821373

  3. Anticancer Activity of Metal Complexes: Involvement of Redox Processes

    PubMed Central

    Jungwirth, Ute; Kowol, Christian R.; Keppler, Bernhard K.; Hartinger, Christian G.; Berger, Walter; Heffeter, Petra

    2012-01-01

    Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e.g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of “activation by reduction” as well as the “hard and soft acids and bases” theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology. PMID:21275772

  4. 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.

  5. Arsenic and 17-β-estradiol bind to each other and neutralize each other's signaling effects.

    PubMed

    Kumar, Sukhdeep; Mukherjee, Tapan K; Guptasarma, Purnananda

    2016-09-01

    We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other's independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D (1)H and (13)C NMR spectroscopy. Binding leads to attenuation of E2's hydroxyl (1)H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other's levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. PMID:27346132

  6. Ascorbic acid combats arsenic-induced oxidative stress in mice liver.

    PubMed

    Banerjee, Pathikrit; Bhattacharyya, Soumya Sundar; Bhattacharjee, Nandini; Pathak, Surajit; Boujedaini, Naoual; Belon, Philippe; Khuda-Bukhsh, Anisur Rahman

    2009-02-01

    Repeated injections of arsenic trioxide induced oxidative stress and hepatotoxicity in mice as revealed from elevated levels of glutamate oxaloacetate transaminases, glutamate pyruvate transaminases, acid and alkaline phosphatases, lipid peroxidation along with reduction of superoxide dismutase, catalase, reduced glutathione content, glutathione reductase and succinate dehydrogenase activities. The present investigation was undertaken to test whether simultaneous feeding of vitamin C can combat hepatotoxicity in arsenic intoxicated mice. Hepatoprotective potential of vitamin C was indicated by its ability to restore GSH, SOD, CAT, AcP, AlkP and GRD levels towards near normal. Electron microscopic studies further supported the biochemical findings confirming the hepatoprotective potential of ascorbic acid. Besides, cytogenetical endpoints (chromosome aberrations, micronuclei, mitotic index and sperm head anomaly) were also analyzed. Administration of vitamin C alone did not show any sign of toxicity of its own. Based on the present findings, ascorbic acid appears to have protective effects against arsenic toxicity and oxidative stress.

  7. 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.

  8. 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

  9. 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...

  10. Anticancer drugs during pregnancy.

    PubMed

    Miyamoto, Shingo; Yamada, Manabu; Kasai, Yasuyo; Miyauchi, Akito; Andoh, Kazumichi

    2016-09-01

    Although cancer diagnoses during pregnancy are rare, they have been increasing with the rise in maternal age and are now a topic of international concern. In some cases, the administration of chemotherapy is unavoidable, though there is a relative paucity of evidence regarding the administration of anticancer drugs during pregnancy. As more cases have gradually accumulated and further research has been conducted, we are beginning to elucidate the appropriate timing for the administration of chemotherapy, the regimens that can be administered with relative safety, various drug options and the effects of these drugs on both the mother and fetus. However, new challenges have arisen, such as the effects of novel anticancer drugs and the desire to bear children during chemotherapy. In this review, we outline the effects of administering cytotoxic anticancer drugs and molecular targeted drugs to pregnant women on both the mother and fetus, as well as the issues regarding patients who desire to bear children while being treated with anticancer drugs. PMID:27284093

  11. 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)

  12. The Form, Distribution and Mobility of Arsenic in Soils Contaminated by Arsenic Trioxide, at Sites in Southeast USA

    SciTech Connect

    Yang,L.; Donahoe, R.

    2007-01-01

    Soils from many industrial sites in southeastern USA are contaminated with As because of the application of herbicide containing As{sub 2}O{sub 3}. Among those contaminated sites, two industrial sites, FW and BH, which are currently active and of most serious environmental concerns, were selected to characterize the occurrence of As in the contaminated soils and to evaluate its environmental leachability. The soils are both sandy loams with varying mineralogical and organic matter contents. Microwave-assisted acid digestion (EPA method 3051) of the contaminated soils indicated As levels of up to 325 mg/kg and 900 mg/kg (dry weight basis) for FW and BH soils, respectively. However, bulk X-ray powder diffraction (XRD) analysis failed to find any detectable As-bearing phases in either of the studied soil samples. Most of the soil As was observed by scanning electron microscopy, coupled with energy dispersive X-ray spectroscopy (SEM/EDX), to be disseminated on the surfaces of fine-grained soil particles in close association with Al and Fe. A few As-bearing particles were detected in BH soil using electron microprobe analysis (EMPA). Synchrotron micro-XRD and X-ray absorption near-edge structure (XANES) analyses indicated that these As-rich particles were possibly phaunouxite, a mineral similar to calcium arsenate, which could have been formed by natural weathering after the application of As{sub 2}O{sub 3}. However, the scarcity of those particles eliminated them from playing any important role in As sequestration. Synthetic acid rain sequential batch leaching experiments showed distinct As leaching behaviors of the two studied soil samples: BH soil, which has the higher As content, showed a slow, steady release of As, while FW soil, with a lower As content, showed a much quicker release and lower overall retention of As upon leaching. Sequential chemical extraction experiments were carried out using a simplified 4-step sequential chemical extraction procedure (SCEP) previously developed to characterize the fractionation of As and better understand the different leaching behaviors of the two studied soils. It was shown that only about 50% of the total extractable As was removed by the first two extraction steps, which represented the most weakly bonded and readily available As for environmental leaching. Compared with the sequential leaching experiments, it was further indicated that only half of the As associated with phases extracted by the second SCEP step was mobilized by SPLP leaching. Although microwave-assisted acid digestion results showed similar Al and Fe contents in both soils, the sequential chemical extraction experiments indicated that BH soil has a much higher content of amorphous Al and Fe phases and that a comparably higher portion of soil As was associated with those materials. The experimental results suggest that remediation efforts for the contaminated sites can be directed towards enhancing the formation of more stable As-bearing compounds in the soils to reduce the environmental leachability of As.

  13. The form, distribution and mobility of arsenic in soilscontaminated by arsenic trioxide, at sites in southeast USA

    SciTech Connect

    Yang, Li; Donahoe, Rona J.

    2005-03-04

    Soils from many industrial sites in southeastern USA arecontaminated with As because of the application of herbicide containingAs2O3. Among those contaminated sites, two industrial sites, FW and BH,which are currently active and of most serious environmental concerns,were selected to characterize the occurrence of As in the contaminatedsoils and to evaluate its environmental leachability. The soils are bothsandy loams with varying mineralogical and organic matter contents.Microwave-assisted acid digestion (EPA method 3051) of the contaminatedsoils indicated As levels of up to 325 mg/kg and 900 mg/kg (dry weightbasis) for FW and BH soils, respectively. However, bulk X-ray powderdiffraction (XRD) analysis failed to find any detectable As-bearingphases in either of the studied soil samples. Most of the soil As wasobserved by scanning electron microscopy, coupled with energy dispersiveX-ray spectroscopy (SEM/EDX), to be disseminated on the surfaces offine-grained soil particles in close association with Al and Fe. A fewAs-bearing particles were detected in BH soil using electron microprobeanalysis (EMPA). Synchrotron micro-XRD and X-ray absorption near-edgestructure (XANES) analyses indicated that these As-rich particles werepossibly phaunouxite, a mineral similar to calcium arsenate, which couldhave been formed by natural weathering after the application of As2O3.However, the scarcity of those particles eliminated them from playing anyimportant role in Assequestration.Synthetic acid rain sequential batchleaching experiments showed distinct As leaching behaviors of the twostudied soil samples: BH soil, which has the higher As content, showed aslow, steady release of As, while FW soil, with a lower As content,showed a much quicker release and lower overall retention of As uponleaching. Sequential chemical extraction experiments were carried outusing a simplified 4-step sequential chemical extraction procedure (SCEP)previously developed to characterize the fractionation of As and betterunderstand the different leaching behaviors of the two studied soils. Itwas shown that only about 50 percent of the total extractable As wasremoved by the first two extraction steps, which represented the mostweakly bonded and readily available As forenvironmental leaching.Compared with the sequential leaching experiments, it was furtherindicated that only half of the As associated with phases extracted bythe second SCEP step was mobilized by SPLP leaching. Althoughmicrowave-assisted acid digestion results showed similar Al and Fecontents in both soils, the sequential chemical extraction experimentsindicated that BH soil has a much higher content of amorphous Al and Fephases and that a comparably higher portion of soil As was associatedwith those materials. The experimental results suggest that remediationefforts for the contaminated sites can be directed towards enhancing theformation of more stable As-bearing compounds in the soils to reduce theenvironmental leachability of As.

  14. The down-regulation of galectin-1 expression is a specific biomarker of arsenic toxicity.

    PubMed

    Chang, Yu-Ying; Chiang, Ming-Chang; Kuo, Tai-Chih; Chi, Li-Ling; Kao, Yung-Hsi; Huang, Rong-Nan

    2011-08-10

    Galectin-1 (GAL1) is known as a β-galactoside-binding protein that also can bind with arsenic to regulate cell functions. Using RNA interference technique, we investigated the possible mechanism involved in GAL1 modulation of arsenite-inhibited cell survival in 3T3 fibroblast and KB oral cancer cells. GAL1 gene knockdown significantly attenuated sodium arsenite (NaAsO(2)) and arsenic trioxide (As(2)O(3)) inhibition of cell survival. However, GAL1 gene knockdown did not alter the inhibition of cell survival by antimony chloride, cadmium chloride or nickel sulfate. These results suggested the GAL1 selectively affects particular types of heavy metal elements. Flow cytometric analysis indicated GAL1 gene knockdown also suppressed As(III)-stimulated levels of sub-G1 and G2/M growth arrest in both cells. Moreover, atomic absorption spectrophotometric results showed that GAL1 gene knockdown reduced the total arsenic accumulation of both cells after the NaAsO(2) and As(2)O(3) treatment. These results suggested that GAL1 gene knockdown mediates the apoptotic effects of arsenic in 3T3 and KB cells via regulation of the cellular arsenic levels. We propose that down-regulation of GAL1 expression may be a useful and specific biomarker in assessing the toxicity of arsenic exposure.

  15. Acute arsenic poisoning treated by intravenous dimercaptosuccinic acid (DMSA) and combined extrarenal epuration techniques.

    PubMed

    Hantson, Philippe; Haufroid, Vincent; Buchet, Jean-Pierre; Mahieu, Paul

    2003-01-01

    Arsenic poisoning was diagnosed in a 26-year-old man who had been criminally intoxicated over the last two weeks preceding admission by the surreptitious oral administration of probably 10 g of arsenic trioxide (As2O3). The patient developed severe manifestations of toxic hepatitis and pancreatitis, and thereafter neurological disorders, respiratory distress, acute renal failure, and cardiovascular disturbances. In addition to supportive therapy, extrarenal elimination techniques and chelating agents were used. Dimercaprol (BAL) and dimercaptosuccinic acid (DMSA or succimer) were used simultaneously as arsenic chelating agents for two days, and thereafter DMSA was used alone. DMSA was administered by intravenous (20 mg/kg/d for five days, then 10 mg/kg/d for six days) and intraperitoneal route. Intravenous DMSA infusion was well tolerated and resulted in an increase in arsenic blood concentration immediately after the infusion. Continuous venovenous hemofiltration combined with hemodialysis, and peritoneal dialysis were proposed to enhance arsenic elimination. It was calculated that over an 11-day period 14.5 mg arsenic were eliminated by the urine, 26.7 mg by hemodialysis, 17.8 mg by peritoneal dialysis, and 7.8 mg by continuous venovenous hemofiltration. These amounts appeared negligible with regard to the probable ingested dose. The patient died on day 26 from the consequences of multiple organ failure, with subarachnoid hemorrhage and generalized infection caused by Aspergillus fumigatus.

  16. The ecology of arsenic.

    PubMed

    Oremland, Ronald S; Stolz, John F

    2003-05-01

    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.

  17. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-10-04

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  18. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Lymphoma or Leukemia

    ClinicalTrials.gov

    2013-01-31

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  19. Transcriptome Profiling of Wheat Seedlings following Treatment with Ultrahigh Diluted Arsenic Trioxide

    PubMed Central

    Betti, Lucietta; Trebbi, Grazia; Borghini, Giovanni; Nani, Daniele; Dinelli, Giovanni

    2014-01-01

    Plant systems are useful research tools to address basic questions in homeopathy as they make it possible to overcome some of the drawbacks encountered in clinical trials (placebo effect, ethical issues, duration of the experiment, and high costs). The objective of the present study was to test the hypothesis whether 7-day-old wheat seedlings, grown from seeds either poisoned with a sublethal dose of As2O3 or unpoisoned, showed different significant gene expression profiles after the application of ultrahigh diluted As2O3 (beyond Avogadro's limit) compared to water (control). The results provided evidence for a strong gene modulating effect of ultrahigh diluted As2O3 in seedlings grown from poisoned seeds: a massive reduction of gene expression levels to values comparable to those of the control group was observed for several functional classes of genes. A plausible hypothesis is that ultrahigh diluted As2O3 treatment induced a reequilibration of those genes that were upregulated during the oxidative stress by bringing the expression levels closer to the basal levels normally occurring in the control plants. PMID:25525452

  20. Retinoic acid plus arsenic trioxide, the ultimate panacea for acute promyelocytic leukemia?

    PubMed

    Lallemand-Breitenbach, Valérie; de Thé, Hugues

    2013-09-19

    Rarely in the field of cancer treatment did we experience as many surprises as with acute promyelocytic leukemia (APL). Yet, the latest clinical trial reported by Lo-Coco et al in the New England Journal of Medicine is a practice-changing study, as it reports a very favorable outcome of virtually all enrolled low-intermediate risk patients with APL without any DNA-damaging chemotherapy. Although predicted from previous small pilot studies, these elegant and stringently controlled results open a new era in leukemia therapy.

  1. Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

    ClinicalTrials.gov

    2016-07-08

    Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

  2. Arsenic trioxide inhibits glioma cell growth through induction of telomerase displacement and telomere dysfunction

    PubMed Central

    Cheng, Ye; Li, Yunqian; Ma, Chengyuan; Song, Yang; Xu, Haiyang; Yu, Hongquan; Xu, Songbai; Mu, Qingchun; Li, Haisong; Chen, Yong; Zhao, Gang

    2016-01-01

    Glioblastomas are resistant to many kinds of treatment, including chemotherapy, radiation and other adjuvant therapies. As2O3 reportedly induces ROS generation in cells, suggesting it may be able to induce telomerase suppression and telomere dysfunction in glioblastoma cells. We show here that As2O3 induces ROS generation as well as telomerase phosphorylation in U87, U251, SHG4 and C6 glioma cells. It also induces translocation of telomerase from the nucleus to the cytoplasm, thereby decreasing total telomerase activity. These effects of As2O3 trigger an extensive DNA damage response at the telomere, which includes up-regulation of ATM, ATR, 53BP1, γ-H2AX and Mer11, in parallel with telomere fusion and 3′-overhang degradation. This ultimately results in induction of p53- and p21-mediated cell apoptosis, G2/M cell cycle arrest and cellular senescence. These results provide new insight into the antitumor effects of As2O3 and can perhaps contribute to solving the problem of glioblastoma treatment resistance. PMID:26871293

  3. Lead-, cadmium-, and arsenic-induced DNA damage in rat germinal cells.

    PubMed

    Nava-Hernández, Martha P; Hauad-Marroquín, Leticia A; Bassol-Mayagoitia, Susana; García-Arenas, Guadalupe; Mercado-Hernández, Roberto; Echávarri-Guzmán, Miguel A; Cerda-Flores, Ricardo M

    2009-05-01

    Toxic agents can interfere with the male reproductive system at many targets. One of the major unresolved questions concerning male infertility is identification of its molecular origins. Clinical and animal studies indicate that abnormalities of spermatogenesis result from exposure to three toxic metals (lead acetate, cadmium chloride, and arsenic trioxide), but the effects on primary spermatocyte DNA of the male rat after chronic exposure to these metals have not been identified. The aims of this study were to analyze, in three independent experiments, the DNA damage induced by lead (Pb), cadmium (Cd), and arsenic (As) in rat germinal cells during three time periods, and to determine the relationship between DNA damage and blood Pb, blood Cd, and urine As levels. For lead acetate and cadmium chloride experiments, blood was collected by cardiac puncture, while for arsenic trioxide a 24-h urine sample was collected. Afterward, the animals were sacrificed by decapitation. Pachytene spermatocytes from rat testes were purified by trypsin digestion followed by centrifugal elutriation. After establishment of cell purity and viability, DNA damage (tail length) was measured employing a single cell gel/comet assay. Significant DNA damage was found in primary spermatocytes from rats with chronic exposure (13 weeks) to toxic metals. In conclusion, these findings indicate that exposure to toxic metals affects primary spermatocyte DNA and are suggestive of possible direct testicular toxicity. PMID:19388847

  4. Anticancer Properties of Lamellarins

    PubMed Central

    Bailly, Christian

    2015-01-01

    In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids. PMID:25706633

  5. Arsenic and cardiovascular disease.

    PubMed

    States, J Christopher; Srivastava, Sanjay; Chen, Yu; Barchowsky, Aaron

    2009-02-01

    Chronic arsenic exposure is a worldwide health problem. Although arsenic-induced cancer has been widely studied, comparatively little attention has been paid to arsenic-induced vascular disease. Epidemiological studies have shown that chronic arsenic exposure is associated with increased morbidity and mortality from cardiovascular disease. In addition, studies suggest that susceptibility to arsenic-induced vascular disease may be modified by nutritional factors in addition to genetic factors. Recently, animal models for arsenic-induced atherosclerosis and liver sinusoidal endothelial cell dysfunction have been developed. Initial studies in these models show that arsenic exposure accelerates and exacerbates atherosclerosis in apolipoprotein E-knockout mice. Microarray studies of liver mRNA and micro-RNA abundance in mice exposed in utero suggest that a permanent state of stress is induced by the arsenic exposure. Furthermore, the livers of the arsenic-exposed mice have activated pathways involved in immune responses suggesting a pro-hyperinflammatory state. Arsenic exposure of mice after weaning shows a clear dose-response in the extent of disease exacerbation. In addition, increased inflammation in arterial wall is evident. In response to arsenic-stimulated oxidative signaling, liver sinusoidal endothelium differentiates into a continuous endothelium that limits nutrient exchange and waste elimination. Data suggest that nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide or its derivatives are essential second messengers in the signaling pathway for arsenic-stimulated vessel remodeling. The recent findings provide future directions for research into the cardiovascular effects of arsenic exposure.

  6. Arsenic and Cardiovascular Disease

    PubMed Central

    States, J. Christopher; Srivastava, Sanjay; Chen, Yu; Barchowsky, Aaron

    2009-01-01

    Chronic arsenic exposure is a worldwide health problem. Although arsenic-induced cancer has been widely studied, comparatively little attention has been paid to arsenic-induced vascular disease. Epidemiological studies have shown that chronic arsenic exposure is associated with increased morbidity and mortality from cardiovascular disease. In addition, studies suggest that susceptibility to arsenic-induced vascular disease may be modified by nutritional factors in addition to genetic factors. Recently, animal models for arsenic-induced atherosclerosis and liver sinusoidal endothelial cell dysfunction have been developed. Initial studies in these models show that arsenic exposure accelerates and exacerbates atherosclerosis in apolipoprotein E–knockout mice. Microarray studies of liver mRNA and micro-RNA abundance in mice exposed in utero suggest that a permanent state of stress is induced by the arsenic exposure. Furthermore, the livers of the arsenic-exposed mice have activated pathways involved in immune responses suggesting a pro-hyperinflammatory state. Arsenic exposure of mice after weaning shows a clear dose-response in the extent of disease exacerbation. In addition, increased inflammation in arterial wall is evident. In response to arsenic-stimulated oxidative signaling, liver sinusoidal endothelium differentiates into a continuous endothelium that limits nutrient exchange and waste elimination. Data suggest that nicotinamide adenine dinucleotide phosphate oxidase–derived superoxide or its derivatives are essential second messengers in the signaling pathway for arsenic-stimulated vessel remodeling. The recent findings provide future directions for research into the cardiovascular effects of arsenic exposure. PMID:19015167

  7. Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells.

    PubMed

    Yajima, Ichiro; Uemura, Noriyuki; Nizam, Saika; Khalequzzaman, Md; Thang, Nguyen D; Kumasaka, Mayuko Y; Akhand, Anwarul A; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

    2012-06-01

    Our fieldwork showed more than 1 μM (145.1 μg/L) barium in about 3 μM (210.7 μg/L) arsenic-polluted drinking well water (n = 72) in cancer-prone areas in Bangladesh, while the mean concentrations of nine other elements in the water were less than 3 μg/L. The types of cancer include squamous cell carcinomas (SCC). We hypothesized that barium modulates arsenic-mediated biological effects, and we examined the effect of barium (1 μM) on arsenic (3 μM)-mediated apoptotic cell death of human HSC-5 and A431 SCC cells in vitro. Arsenic promoted SCC apoptosis with increased reactive oxygen species (ROS) production and JNK1/2 and caspase-3 activation (apoptotic pathway). In contrast, arsenic also inhibited SCC apoptosis with increased NF-κB activity and X-linked inhibitor of apoptosis protein (XIAP) expression level and decreased JNK activity (antiapoptotic pathway). These results suggest that arsenic bidirectionally promotes apoptotic and antiapoptotic pathways in SCC cells. Interestingly, barium in the presence of arsenic increased NF-κB activity and XIAP expression and decreased JNK activity without affecting ROS production, resulting in the inhibition of the arsenic-mediated apoptotic pathway. Since the anticancer effect of arsenic is mainly dependent on cancer apoptosis, barium-mediated inhibition of arsenic-induced apoptosis may promote progression of SCC in patients in Bangladesh who keep drinking barium and arsenic-polluted water after the development of cancer. Thus, we newly showed that barium in the presence of arsenic might inhibit arsenic-mediated cancer apoptosis with the modulation of the balance between arsenic-mediated promotive and suppressive apoptotic pathways.

  8. Sesterterpenoids with Anticancer Activity

    PubMed Central

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2016-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  9. Arsenic Exposure and Glucose Intolerance/Insulin Resistance in Estrogen-Deficient Female Mice

    PubMed Central

    Huang, Chun-Fa; Yang, Ching-Yao; Chan, Ding-Cheng; Wang, Ching-Chia; Huang, Kuo-How; Wu, Chin-Ching; Tsai, Keh-Sung; Yang, Rong-Sen

    2015-01-01

    Background Epidemiological studies have reported that the prevalence of diabetes in women > 40 years of age, especially those in the postmenopausal phase, was higher than in men in areas with high levels of arsenic in drinking water. The detailed effect of arsenic on glucose metabolism/homeostasis in the postmenopausal condition is still unclear. Objectives We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice. Methods Adult female mice who underwent ovariectomy or sham surgery were exposed to drinking water contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence of 17β-estradiol supplementation for 2–6 weeks. Assays related to glucose metabolism were performed. Results Exposure of sham mice to arsenic significantly increased blood glucose, decreased plasma insulin, and impaired glucose tolerance, but did not induce insulin resistance. Blood glucose and insulin were higher, and glucose intolerance, insulin intolerance, and insulin resistance were increased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Furthermore, liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was increased and liver glycogen content was decreased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Glucose-stimulated insulin secretion in islets isolated from arsenic-treated ovariectomized mice was also significantly decreased. Arsenic treatment significantly decreased plasma adiponectin levels in sham and ovariectomized mice. Altered glucose metabolism/homeostasis in arsenic-treated ovariectomized mice was reversed by 17β-estradiol supplementation. Conclusions Our findings suggest that estrogen deficiency plays an important role in arsenic-altered glucose metabolism/homeostasis in females. Citation Huang CF, Yang CY, Chan DC, Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic

  10. Arsenic: the forgotten poison?

    PubMed

    Barton, E N; Gilbert, D T; Raju, K; Morgan, O S

    1992-03-01

    Chronic arsenic poisoning is an uncommon cause of peripheral neuropathy in Jamaica. A patient with this disorder is described. The insidious nature of chronic arsenic poisoning, with its disabling complications, is emphasised.

  11. Toxic Substances Portal- Arsenic

    MedlinePlus

    ... industrial applications. Organic arsenic compounds are used as pesticides, primarily on cotton fields and orchards. top What ... as copper or lead smelting, wood treating, or pesticide application. top How can arsenic affect my health? ...

  12. Cryptic exposure to arsenic.

    PubMed

    Rossy, Kathleen M; Janusz, Christopher A; Schwartz, Robert A

    2005-01-01

    Arsenic is an odorless, colorless and tasteless element long linked with effects on the skin and viscera. Exposure to it may be cryptic. Although human intake can occur from four forms, elemental, inorganic (trivalent and pentavalent arsenic) and organic arsenic, the trivalent inorganic arsenicals constitute the major human hazard. Arsenic usually reaches the skin from occupational, therapeutic, or environmental exposure, although it still may be employed as a poison. Occupations involving new technologies are not exempt from arsenic exposure. Its acute and chronic effects are noteworthy. Treatment options exist for arsenic-induced pathology, but prevention of toxicity remains the main focus. Vitamin and mineral supplementation may play a role in the treatment of arsenic toxicity. PMID:16394429

  13. Cryptic exposure to arsenic.

    PubMed

    Rossy, Kathleen M; Janusz, Christopher A; Schwartz, Robert A

    2005-01-01

    Arsenic is an odorless, colorless and tasteless element long linked with effects on the skin and viscera. Exposure to it may be cryptic. Although human intake can occur from four forms, elemental, inorganic (trivalent and pentavalent arsenic) and organic arsenic, the trivalent inorganic arsenicals constitute the major human hazard. Arsenic usually reaches the skin from occupational, therapeutic, or environmental exposure, although it still may be employed as a poison. Occupations involving new technologies are not exempt from arsenic exposure. Its acute and chronic effects are noteworthy. Treatment options exist for arsenic-induced pathology, but prevention of toxicity remains the main focus. Vitamin and mineral supplementation may play a role in the treatment of arsenic toxicity.

  14. Arsenic and atherosclerosis.

    PubMed

    Simeonova, Petia P; Luster, Michael I

    2004-08-01

    Epidemiological studies have demonstrated a correlation between environmental or occupational arsenic exposure and a risk of vascular diseases related to atherosclerosis. Studies summarized in this review suggest that arsenic induces endothelial dysfunction, including inflammatory and coagulating activity as well as impairs nitric oxide (NO) balance. This may provide the pathophysiological basis for atherogenic potential of arsenic. Consistent with these data, arsenic accelerates atherosclerosis in apolipoprotein E (ApoE) deficient mice, a model of human atherosclerosis.

  15. Notoriety to respectability: a short history of arsenic prior to its present day use in haematology.

    PubMed

    Doyle, Derek

    2009-05-01

    This paper looks at arsenic, and in particular the trioxide, from the days of the ancient Chinese, Egyptians, Greeks and Romans, through the 17th-20th centuries to its adoption by today's haematologists. It looks at its commercial and medical uses, past and present, its notoriety as a poison, it's reputation as a 'tonic' and therapeutic agent, many of the famous people associated with it including Thomas Fowler, William Withering and Robert Christison, and the promise an 18th century panacea now offers 21st century patients under the care of today's haematologists and tomorrow's oncologists.

  16. Response to Comment on "SUMO deconjugation is required for arsenic-triggered ubiquitylation of PML".

    PubMed

    Fasci, Domenico; Anania, Veronica; Lill, Jennie; Salvesen, Guy

    2016-01-01

    Arsenic trioxide chemotherapy cures acute promyelocytic leukemia by inducing the ubiquitylation of an oncogenic fusion protein containing promyelocytic leukemia protein (PML) subsequent to modification of PML by SUMO1 and SUMO2. We proposed that the SUMO switch at Lys(65) of PML enhanced subsequent SUMO2 conjugation to Lys(160) and consequent RNF4-dependent ubiquitylation of PML. Ferhi et al note differences between their experimental system and ours regarding the outcome and mechanisms of SUMO-dependent PML signaling. When confronted by apparently contradictory data, it is appropriate to drill down to where the differences could lie. PMID:27507652

  17. 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 ...

  18. Arsenic in Food

    MedlinePlus

    ... inorganic forms. The FDA has been measuring total arsenic concentrations in foods, including rice and juices, through its Total Diet Study program ... readily take up much arsenic from the ground, rice is different because it takes ... has high levels of less toxic organic arsenic. Do organic foods ...

  19. The carcinogenicity of arsenic.

    PubMed Central

    Pershagen, G

    1981-01-01

    A carcinogenic role of inorganic arsenic has been suspected for nearly a century. Exposure to inorganic arsenic compounds occurs in some occupational groups, e.g., among smelter workers and workers engaged in the production and use of arsenic containing pesticides. Substantial exposure can also result from drinking water in certain areas and the use of some drugs. Tobacco and wine have had high As concentrations due to the use of arsenic containing pesticides. Inorganic arsenic compounds interfere with DNA repair mechanisms and an increased frequency of chromosomal aberrations have been observed among exposed workers and patients. Epidemiological data show that inorganic arsenic exposure can cause cancer of the lung and skin. The evidence of an etiologic role of arsenic for angiosarcoma of the liver is highly suggestive; however, the association between arsenic and cancer of other sites needs further investigation. No epidemiological data are available on exposure to organic arsenic compounds and cancer. Animal carcinogenicity studies involving exposure to various inorganic and organic arsenic compounds by different routes have been negative, with the possible exception of some preliminary data regarding lung cancer and leukemia. Some studies have indicated an increased mortality from lung cancer in populations living near point emission sources of arsenic into the air. The role of arsenic cannot be evaluated due to lack of exposure data. Epidemiological data suggest that the present WHO standard for drinking water (50 micrograms As/l.) provides only a small safety margin with regard to skin cancer. PMID:7023936

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Melatonin Anticancer Effects: Review

    PubMed Central

    Di Bella, Giuseppe; Mascia, Fabrizio; Gualano, Luciano; Di Bella, Luigi

    2013-01-01

    Melatonin (N-acetyl-5-methoxytryptamine, MLT), the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate). The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation). All these particular characteristics suggest the use of MLT in oncological diseases. PMID:23348932

  6. 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...

  7. Mineral Trioxide Aggregate and Portland Cement for Direct Pulp Capping in Dog: A Histopathological Evaluation

    PubMed Central

    Bidar, Maryam; Naghavi, Neda; Mohtasham, Nooshin; Sheik-Nezami, Mahshid; Fallahrastegar, Amir; Afkhami, Farzaneh; Attaran Mashhadi, Negin; Nargesi, Iman

    2014-01-01

    Background and aims. Mineral trioxide aggregate and calcium hydroxide are considered the gold standard pulp-capping materials. Recently, Portland cement has been introduced with properties similar to those of mineral trioxide aggregate. Histopathological effects of direct pulp capping using mineral trioxide aggregate and Portland cements on dog dental pulp tissue were evaluated in the present study. Materials and methods. This histopatological study was carried out on 64 dog premolars. First, the pulp was exposed with a sterile bur. Then, the exposed pulp was capped with white or gray mineral trioxide aggregates and white or gray Portland cements in each quadrant and sealed with glass-ionomer. The specimens were evaluated under a light microscope after 6 months. Statistical analysis was carried out using Kruskal-Wallis test. Statistical significance was defined at α=5%. Results. There was no acute inflammation in any of the specimens. Chronic inflammation in white and gray mineral trioxide aggregates and white and gray Portland cements was reported to be 45.5%, 27.3%, 57.1% and 34.1%, respectively. Although the differences were not statistically significant, severe inflammation was observed mostly adjacent to white mineral trioxide aggregate. The largest extent of increased vascularization (45%) and the least increase in fibrous tissue were observed adjacent to white mineral trioxide aggregate, with no significant differences. In addition, the least calcified tissue formed adjacent to white mineral trioxide aggregate, although the difference was not significant. Conclusion. The materials used in this study were equally effective as pulp protection materials following direct pulp capping in dog teeth. PMID:25346831

  8. Electrochromic properties of molybdenum trioxide thin films prepared by chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Maruyama, Toshiro; Kanagawa, Tetsuya

    1995-05-01

    Electrochromic molybdenum trioxide thin films were prepared by chemical vapor deposition. The source material was molybdenum carbonyl. Amorphous molybdenum trioxide thin films were produced at a substrate temperature 300 C. Reduction and oxidation of the films in a 0.3M LiClO4 propylene carbon ate solution caused desirable changes in optical absorption. Coulometry indicated that the coloration efficiency was 25.8 sq cm center-dot C(exp -1).

  9. Mineral trioxide aggregate (MTA)-like materials: an update review.

    PubMed

    Mohammadi, Zahed; Shalavi, Sousan; Soltani, Mohammad Karim

    2014-09-01

    Mineral trioxide aggregate (MTA) is a multi-application material used in endodontics. It is a mixture of a refined Portland cement and bismuth oxide and trace amounts of SiO₂, CaO, MgO, K₂SO₄, and Na₂SO₄. MTA powder is mixed with supplied sterile water in a 3:1 powder/liquid. Hydrated MTA has an initial pH of 10.2, which rises to 12.5 three hours after mixing. There are several materials derived from MTA such as Endo-CPM Sealer, Ortho MTA, MTA-Fillapex, DiaRoot BioAggregate, MTA Bio, light-cured MTA, tricalcium silicate, and iRoot SP. The purpose of this article is to review MTA-like materials. PMID:25199028

  10. Clinical Applications of Mineral Trioxide Aggregate: Report of Four Cases

    PubMed Central

    Battepati, Prashant M

    2010-01-01

    The greatest threats to developing teeth are dental caries and traumatic injuries. The primary goal of all restorative treatment is to maintain pulp vitality so that normal root development or apexogenesis can occur. If pulpal exposure occurs, then a pulpotomy procedure aims to preserve pulp vitality to allow for normal root development. Historically, calcium hydroxide has been the material of choice for pulpotomy procedures. Recently, an alternative material called mineral trioxide aggregate (MTA) has demonstrated the ability to induce hard-tissue formation in pulpal tissue. This article describes the clinical and radiographic outcome of a series of cases involving the use of MTA in pulpotomy, apexogenesis and apexification procedures and root perforations repair.

  11. Chemical characteristics of mineral trioxide aggregate and its hydration reaction

    PubMed Central

    2012-01-01

    Mineral trioxide aggregate (MTA) was developed in early 1990s and has been successfully used for root perforation repair, root end filling, and one-visit apexification. MTA is composed mainly of tricalcium silicate and dicalcium silicate. When MTA is hydrated, calcium silicate hydrate (CSH) and calcium hydroxide is formed. Formed calcium hydroxide interacts with the phosphate ion in body fluid and form amorphous calcium phosphate (ACP) which finally transforms into calcium deficient hydroxyapatite (CDHA). These mineral precipitate were reported to form the MTA-dentin interfacial layer which enhances the sealing ability of MTA. Clinically, the use of zinc oxide euginol (ZOE) based materials may retard the setting of MTA. Also, the use of acids or contact with excessive blood should be avoided before complete set of MTA, because these conditions could adversely affect the hydration reaction of MTA. Further studies on the chemical nature of MTA hydration reaction are needed. PMID:23429542

  12. Mineral trioxide aggregate (MTA)-like materials: an update review.

    PubMed

    Mohammadi, Zahed; Shalavi, Sousan; Soltani, Mohammad Karim

    2014-09-01

    Mineral trioxide aggregate (MTA) is a multi-application material used in endodontics. It is a mixture of a refined Portland cement and bismuth oxide and trace amounts of SiO₂, CaO, MgO, K₂SO₄, and Na₂SO₄. MTA powder is mixed with supplied sterile water in a 3:1 powder/liquid. Hydrated MTA has an initial pH of 10.2, which rises to 12.5 three hours after mixing. There are several materials derived from MTA such as Endo-CPM Sealer, Ortho MTA, MTA-Fillapex, DiaRoot BioAggregate, MTA Bio, light-cured MTA, tricalcium silicate, and iRoot SP. The purpose of this article is to review MTA-like materials.

  13. Chemical characteristics of mineral trioxide aggregate and its hydration reaction.

    PubMed

    Chang, Seok-Woo

    2012-11-01

    Mineral trioxide aggregate (MTA) was developed in early 1990s and has been successfully used for root perforation repair, root end filling, and one-visit apexification. MTA is composed mainly of tricalcium silicate and dicalcium silicate. When MTA is hydrated, calcium silicate hydrate (CSH) and calcium hydroxide is formed. Formed calcium hydroxide interacts with the phosphate ion in body fluid and form amorphous calcium phosphate (ACP) which finally transforms into calcium deficient hydroxyapatite (CDHA). These mineral precipitate were reported to form the MTA-dentin interfacial layer which enhances the sealing ability of MTA. Clinically, the use of zinc oxide euginol (ZOE) based materials may retard the setting of MTA. Also, the use of acids or contact with excessive blood should be avoided before complete set of MTA, because these conditions could adversely affect the hydration reaction of MTA. Further studies on the chemical nature of MTA hydration reaction are needed. PMID:23429542

  14. Environmental management of sulfur trioxide emission: impact of SO3 on human health.

    PubMed

    Kikuchi, R

    2001-06-01

    The major contributors to global acidification are sulfur oxides and nitrogen oxides emitted mostly by the burning of fossil fuels. From the scientific point of view, it is necessary to make a clear distinction between sulfur dioxide and sulfur trioxide when referring to sulfur oxides. These two air pollutants have different properties. This paper reports the following aspects: the strong effect of sulfur trioxide on local human health (a case study of asthma in Yokkaichi), the problem of corrosion caused by sulfur trioxide, the difference in analytical methods for determining sulfur dioxide concentrations and sulfur trioxide concentrations, and the difference in removal methods for sulfur dioxide and sulfur trioxide. An important initiative at the third European conference of environment ministers was that the issue of human health related to local air pollution should be given priority over that of global pollution. The declines in the emissions of sulfur dioxide and nitrogen oxides have mainly been effective in reducing acidification due to long-range transport. The reduction in sulfur trioxide may be more effective in improving local human health mentioned in the initiative.

  15. Anticancer substances of mushroom origin.

    PubMed

    Ivanova, T S; Krupodorova, T A; Barshteyn, V Y; Artamonova, A B; Shlyakhovenko, V A

    2014-06-01

    The present status of investigations about the anticancer activity which is inherent to medicinal mushrooms, as well as their biomedical potential and future prospects are discussed. Mushroom products and extracts possess promising immunomodulating and anticancer effects, so the main biologically active substances of mushrooms responsible for immunomodulation and direct cytoto-xicity toward cancer cell lines (including rarely mentioned groups of anticancer mushroom proteins), and the mechanisms of their antitumor action were analyzed. The existing to date clinical trials of mushroom substances are mentioned. Mushroom anticancer extracts, obtained by the different solvents, are outlined. Modern approaches of cancer treatment with implication of mushroom products, including DNA vaccinotherapy with mushroom immunomodulatory adjuvants, creation of prodrugs with mushroom lectins that can recognize glycoconjugates on the cancer cell surface, development of nanovectors etc. are discussed. The future prospects of mushroom anticancer substances application, including chemical modification of polysaccharides and terpenoids, gene engineering of proteins, and implementation of vaccines are reviewed.

  16. Acute arsenic poisoning: absence of polyneuropathy after treatment with 2,3-dimercaptopropanesulphonate (DMPS).

    PubMed

    Moore, D F; O'Callaghan, C A; Berlyne, G; Ogg, C S; Davies, H A; House, I M; Henry, J A

    1994-09-01

    Two men aged 19 and 21 years ingested 1 g and 4 g respectively from 3 kg of a white crystalline powder that they thought was a substance of abuse. It was later identified as almost pure arsenic trioxide. Both had nausea and vomiting and one developed acute renal failure. Each was treated with 2,3-dimercaptopropanesulphonate (DMPS), and made a full recovery with no evidence of prolonged renal or neurological impairment. The DMPS-arsenic complex is probably associated with lower penetration into the CNS and as a consequence treatment with DMPS may result in lower acute and chronic neurotoxicity than treatment with the currently standard recommended chelating agent dimercaprol (British Anti-Lewisite; BAL).

  17. Anticancer mechanisms of cannabinoids.

    PubMed

    Velasco, G; Sánchez, C; Guzmán, M

    2016-03-01

    In addition to the well-known palliative effects of cannabinoids on some cancer-associated symptoms, a large body of evidence shows that these molecules can decrease tumour growth in animal models of cancer. They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival. In addition, cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals. In this review, we discuss the current understanding of cannabinoids as antitumour agents, focusing on recent discoveries about their molecular mechanisms of action, including resistance mechanisms and opportunities for their use in combination therapy. Those observations have already contributed to the foundation for the development of the first clinical studies that will analyze the safety and potential clinical benefit of cannabinoids as anticancer agents.

  18. Anticancer mechanisms of cannabinoids

    PubMed Central

    Velasco, G.; Sánchez, C.; Guzmán, M.

    2016-01-01

    In addition to the well-known palliative effects of cannabinoids on some cancer-associated symptoms, a large body of evidence shows that these molecules can decrease tumour growth in animal models of cancer. They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival. In addition, cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals. In this review, we discuss the current understanding of cannabinoids as antitumour agents, focusing on recent discoveries about their molecular mechanisms of action, including resistance mechanisms and opportunities for their use in combination therapy. Those observations have already contributed to the foundation for the development of the first clinical studies that will analyze the safety and potential clinical benefit of cannabinoids as anticancer agents. PMID:27022311

  19. Carotidynia after anticancer chemotherapy

    PubMed Central

    Hayashi, Shinichi; Maruoka, Shuichiro; Takahashi, Noriaki; Hashimoto, Shu

    2014-01-01

    Carotidynia is characterised by inflammation limited to the common carotid artery, which has been recognised as a distinct disease entity by advanced vascular imaging. Although most cases of carotidynia are idiopathic, we herein present a case of carotidynia after anticancer chemotherapy. A 64-year-old male patient received docetaxel followed by granulocyte-colony stimulating factor (G-CSF) for the treatment of lung squamous carcinoma. After the treatment, bilateral cervical pain developed. Vascular imaging, including magnetic resonance imaging, computed tomography and ultrasonography, showed characteristics specific for carotidynia. Although there was no strong confirmation using tests such as a challenge test, our observations suggest that docetaxel or G-CSF could be a causative drug triggering carotidynia. PMID:25273942

  20. Acute arsenic intoxication.

    PubMed

    Campbell, J P; Alvarez, J A

    1989-12-01

    The diagnosis of acute arsenic poisoning should be considered in any patient presenting with severe gastrointestinal complaints. Signs and symptoms include nausea, vomiting, colicky abdominal pain and profuse, watery diarrhea. Hypotension, fluid and electrolyte disturbances, mental status changes, electrocardiographic abnormalities, respiratory failure and death can result. Quantitative measurement of 24-hour urinary arsenic excretion is the only reliable laboratory test to confirm arsenic poisoning. Treatment includes gastric emesis or lavage, chelation therapy, electrolyte and fluid replacement, and cardiorespiratory support.

  1. [Chronic arsenic poisoning].

    PubMed

    Lozano Armando, V; Ochoa Angel, A

    1979-01-01

    A case of chronic arsenic intoxication due to ingestion of contaminated water for several years is reported. The main symptoms were keratosis palmaris et plantaris, confetti - Like dyschromias in chest, post - necrotic liver cirrhosis multiple intraepithelial epidermoid carcinomas and invasive epidermoid carcinoma. The epidemiologic study showed high concentration of arsenic in the water of the well used by the patient; likewise, chronic arsenicalism was found in the whole family and in several neighbors who consumed water from the same well.

  2. SUMO deconjugation is required for arsenic-triggered ubiquitylation of PML

    PubMed Central

    Fasci, Domenico; Anania, Veronica G.; Lill, Jennie R.; Salvesen, Guy S.

    2015-01-01

    Acute promyelocytic leukemia is characterized by a chromosomal translocation that produces an oncogenic fusion protein of the retinoic acid receptor α (RARα) and promyelocytic leukemia protein (PML). Arsenic trioxide chemotherapy of this cancer induces the PML moiety to organize nuclear bodies, where the oncoprotein is degraded. This process requires the participation of two SUMO paralogs (SUMO1 and SUMO2) to promote PML ubiquitylation mediated by the ubiquitin E3 ligase RNF4 and reorganization of PML nuclear bodies. We demonstrated that the ubiquitylation of PML required the SUMO deconjugation machinery, primarily the deconjugating enzyme SENP1, and was suppressed by expression of non-deconjugatable SUMO2. We hypothesized that constitutive SUMO2 conjugation and deconjugation occurred basally, and that arsenic trioxide treatment caused the exchange of SUMO2 for SUMO1 on a fraction of Lys65 in PML. Based on data obtained with mutational analysis and quantitative proteomics, we propose that the SUMO switch at Lys65 of PML enhanced nuclear body formation, subsequent SUMO2 conjugation to Lys160, and consequent RNF4-dependent ubiquitylation of PML. Our work provides insights into how the SUMO system achieves selective SUMO paralog modification, and highlights the crucial role of SENPs in defining the specificity of SUMO signaling. PMID:26060329

  3. Arsenic compounds and cancer.

    PubMed

    Axelson, O

    1980-01-01

    Exposure to arsenic compounds has been epidemiologically associated with various types of cancers, particularly cancer of the lung among copper smelters and pesticide workers, whereas skin cancers and liver angiosarcomas have been associated with ingestion of arsenic for treatment of skin disorders, especially psoriasis. Attempts to reproduce cancer in animals have been mainly unsuccessful, however. Experimental evidence suggests that arsenic inhibits DNA repair; this might help to explain the somewhat conflicting observations from epidemiologic studies and animal experiments with regard to carcinogenicity, and perhaps also cardiovascular morbidity related to arsenic exposure. PMID:7463514

  4. Protective effect of naringenin on hepatic and renal dysfunction and oxidative stress in arsenic intoxicated rats.

    PubMed

    Mershiba, Sam Daniel; Dassprakash, M Velayutham; Saraswathy, Sundara Dhakshinamurthy

    2013-05-01

    Arsenic has a long history as a potent human poison, chronic exposure over a period of time may result in the manifestation of toxicity in practically all systems of the body. In the present investigation the efficacy of naringenin (NRG), a naturally occurring citrus flavanone against arsenic-induced hepatotoxic and nephrotoxic manifestations have been studied in rats. Arsenic trioxide was administered orally at the dose of 2 mg/kg/day with or without combination of NRG (20 or 50 mg/kg/day) for 28 days. At the end of the experimental period the hepatic and renal dysfunction was evaluated by histological examination, serum biomarkers and markers of oxidative stress; lipid peroxidation (LPO), reduced glutathione (GSH) and antioxidant enzymes. Arsenic intoxication increased serum bilirubin, urea, uric acid and creatinine levels, additionally enhanced the activities of hepatic marker enzymes aspartate transaminase, alanine transaminase and alkaline phosphatase. Also, the hepatic and renal tissues showed a marked elevation in LPO levels with a decrease in GSH content and the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase on arsenic treatment. Simultaneous treatment with NRG restored the activities of serum biomarkers and antioxidant enzymes in the tissues in a dose-dependent manner. Furthermore, the histopathological studies confirmed the protective effect of NRG co-treatment by reducing the pathological changes due to arsenic intoxication in both liver and kidney. Thus, our present study demonstrates that NRG has a potential to protect arsenic-induced oxidative hepatic and renal dysfunction. PMID:23283742

  5. High pseudotumor cerebri incidence in tretinoin and arsenic treated acute promyelocytic leukemia and the role of topiramate after acetazolamide failure

    PubMed Central

    Smith, Morgan B.; Griffiths, Elizabeth A.; Thompson, James E.; Wang, Eunice S.; Wetzler, Meir; Freyer, Craig W.

    2014-01-01

    Dual differentiation therapy with arsenic trioxide and tretinoin (all-trans-retinoic acid; ATRA) for the management of low and intermediate risk acute promyelocytic leukemia has recently been recommended by the National Comprehensive Cancer Network. Some less common toxicities of the combination may have yet to be fully realized. Of ten patients we have treated thus far, five (50%) have developed pseudotumor cerebri. In one patient, temporary discontinuation of ATRA and initiation of acetazolamide controlled symptoms. In four patients, topiramate was substituted for acetazolamide to relieve symptoms and allow ATRA dose re-escalation. We conclude that providers should monitor for pseudotumor cerebri and consider topiramate if acetazolamide fails. PMID:25180154

  6. 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...

  7. Arsenic (Environmental Health Student Portal)

    MedlinePlus

    ... Natural Disasters Drinking Water Waterborne Diseases & Illnesses Water Cycle Water Treatment Arsenic The Basics Arsenic is an element that exists naturally in the Earth’s crust. Small amounts of arsenic are found in some rock, soil, water, and air. When arsenic combines with ...

  8. [Multiple bowenoid arsenic keratoses].

    PubMed

    Leyh, F; Rothlaender, J P

    1985-01-01

    Case report of multiple keratoses and chronic lymphatic leukemia after arsenic poisoning 30 years ago during a one-year exposure to copper acetoarsenate in a pesticide factory. Absorption through the skin with local arsenic skin damage is discussed. Etretinate therapy (1 mg/kg b. w.) was ineffective.

  9. 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.

  10. 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.

  11. An update on arsenic

    SciTech Connect

    Malachowski, M.E. )

    1990-09-01

    Arsenic poisoning is more than just a medical curiosity. Cases of acute and chronic intoxication continue to occur in the United States. Much is now known about the biochemical mechanisms of injury, which has led to a rational basis for therapy. Most importantly, however, the clinician must stay alert to correctly diagnose and treat cases of arsenic poisoning.23 references.

  12. ARSENIC AND OHIO UTILITIES

    EPA Science Inventory

    The presentation provides information on arsenic removal drinking water treatment systems that are likely to be used in Ohio for arsenic removal. Because most Ohio ground water contain significant amounts of iron, iron removal processes will play a major role in treating Ohio gro...

  13. Photoresist removal using gaseous sulfur trioxide cleaning technology

    NASA Astrophysics Data System (ADS)

    Del Puppo, Helene; Bocian, Paul B.; Waleh, Ahmad

    1999-06-01

    A novel cleaning method for removing photoresists and organic polymers from semiconductor wafers is described. This non-plasma method uses anhydrous sulfur trioxide gas in a two-step process, during which, the substrate is first exposed to SO3 vapor at relatively low temperatures and then is rinsed with de-ionized water. The process is radically different from conventional plasma-ashing methods in that the photoresist is not etched or removed during the exposure to SO3. Rather, the removal of the modified photoresist takes place during the subsequent DI-water rinse step. The SO3 process completely removes photoresist and polymer residues in many post-etch applications. Additional advantages of the process are absence of halogen gases and elimination of the need for other solvents and wet chemicals. The process also enjoys a very low cost of ownership and has minimal environmental impact. The SEM and SIMS surface analysis results are presented to show the effectiveness of gaseous SO3 process after polysilicon, metal an oxide etch applications. The effects of both chlorine- and fluorine-based plasma chemistries on resist removal are described.

  14. Mineral trioxide aggregate: a review of physical properties.

    PubMed

    Malhotra, Neeraj; Agarwal, Antara; Mala, Kundabala

    2013-02-01

    The purpose of this two-part series is to review the composition, properties, products, and clinical aspects of mineral trioxide aggregate (MTA) materials. Electronic search of scientific papers from January 1991 to May 2010 was accomplished using PubMed and MedLine search engines to include relevant scientific citations from the peer-reviewed journals published in English. MTA is a refined form of the parent compound, Portland cement (PC). It demonstrates a strong biocompatible nature owing to the high pH and its ability to form hydroxyapatite. MTA materials provide a better seal than traditional endodontic materials as observed in dye leakage, fluid filtration, protein leakage, and bacterial penetration leakage studies, and it has been recognized as a bioactive material. Currently a variety of MTA commercial products are available, including Proroot Gray MTA and White MTA both from DENTSPLY Tulsa Dental Specialties (www.DENTSPLY.com), and MTA Angelus (Angelus,www.angelus.ind.br). Although these materials are indicated for various dental uses/applications, long-term in-vivo clinical studies are still needed to claim the same. This first of this series highlights and discusses the composition, physical, and/or chemical properties of MTA. A subsequent article will offer an overview of the material aspect (commercial products) and clinical considerations for MTA materials.

  15. Compressive Strength of Mineral Trioxide Aggregate with Propylene Glycol

    PubMed Central

    Ghasemi, Negin; Rahimi, Saeed; Shahi, Shahriar; Salem Milani, Amin; Rezaei, Yashar; Nobakht, Mahnaz

    2016-01-01

    Introduction: The aim of this study was to evaluate the effect of adding propylene glycol (PG) to mineral trioxide aggregate (MTA) liquid with volume ratio of 20% on the compressive strength (CS) of MTA in two time periods (4 and 21 days) after mixing. Methods and Materials: Four groups of steel cylinders (n=15) with an internal diameter of 3 and a height of 6 mm were prepared and MTA (groups 1 and 2) and MTA+PG (80% MTA liquid+20% PG) (groups 3 and 4) were placed in to the cylinders. In groups 1 and 3 the CS was evaluated after 4 days and in groups 2 and 4 after 21 days. Data were calculated using the two-ways ANOVA. The level of significance was set at 0.05. Results: The highest (52.22±18.92 MPa) and lowest (4.5±0.67 MPa) of CS was obtained in 21-day MTA samples and 4-day MTA+PG specimen, respectively. The effect of time and PG were significant on the CS (P<0.05). Mixing MTA with PG significantly reduced the CS; but passing the time from 4 to 21 days significantly increased the CS. Conclusion: Considering the limitations of this study, PG had a negative effect on CS of MTA. PMID:27790264

  16. Uranium trioxide behavior during electron energy loss spectroscopy analysis

    NASA Astrophysics Data System (ADS)

    Degueldre, Claude; Alekseev, Evgeny V.

    2015-03-01

    A sample of uranium trioxide (UO3) was produced by focused ion beam (~10 μm×~10 μm×<0.5 μm) for transmission electron and electron energy loss (EEL) spectroscopy examinations in a transmission electron microscope (TEM). The EEL spectra were recorded as a function of the thickness for the P and O edges in the low energy range 0-350 eV and were compared to spectra of UO3 small grains attached to a TEM grid. The EEL spectrum was studied through a range of thicknesses going from ~60 to ~260 nm. The EEL spectra recorded for UO3 are compared with those recorded for UO2. The reduction of UO3 into U4O9 and/or UO2 is readily observed apparently during the TEM investigations and as confirmed by electron diffraction (eD). This redox effect is similar to that known for other redox sensitive oxides. Recommendations are suggested to avoid sample decomposition.

  17. Kinetics and mechanism of photopromoted oxidative dissolution of antimony trioxide.

    PubMed

    Hu, Xingyun; Kong, Linghao; He, Mengchang

    2014-12-16

    Light (sunlight, ultraviolet, simulated sunlight) irradiation was used to initiate the dissolution of antimony trioxide (Sb2O3). Dissolution rate of Sb2O3 was accelerated and dissolved trivalent antimony (Sb(III)) was oxidized in the irradiation of light. The photopromoted oxidative dissolution mechanism of Sb2O3 was studied through experiments investigating the effects of pH, free radicals scavengers, dissolved oxygen removal and Sb2O3 dosage on the release rate of antimony from Sb2O3 under simulated sunlight irradiation. The key oxidative components were hydroxyl free radicals, photogenerated holes and superoxide free radicals; their contribution ratios were roughly estimated. In addition, a conceptual model of the photocatalytic oxidation dissolution of Sb2O3 was proposed. The overall pH-dependent dissolution rate of Sb2O3 and the oxidation of Sb(III) under light irradiation were expressed by r = 0.08 ·[OH(-)](0.63) and rox = 0.10 ·[OH(-)](0.79). The present study on the mechanism of the photo-oxidation dissolution of Sb2O3 could help clarify the geochemical cycle and fate of Sb in the environment.

  18. Liquid phase deposition synthesis of hexagonal molybdenum trioxide thin films

    SciTech Connect

    Deki, Shigehito; Beleke, Alexis Bienvenu; Kotani, Yuki; Mizuhata, Minoru

    2009-09-15

    Hexagonal molybdenum trioxide thin films with good crystallinity and high purity have been fabricated by the liquid phase deposition (LPD) technique using molybdic acid (H{sub 2}MoO{sub 4}) dissolved in 2.82% hydrofluoric acid (HF) and H{sub 3}BO{sub 3} as precursors. The crystal was found to belong to a hexagonal hydrate system MoO{sub 3}.nH{sub 2}O (napprox0.56). The unit cell lattice parameters are a=10.651 A, c=3.725 A and V=365.997 A{sup 3}. Scanning electron microscope (SEM) images of the as-deposited samples showed well-shaped hexagonal rods nuclei that grew and where the amount increased with increase in reaction time. X-ray photon electron spectroscopy (XPS) spectra showed a Gaussian shape of the doublet of Mo 3d core level, indicating the presence of Mo{sup 6+} oxidation state in the deposited films. The deposited films exhibited an electrochromic behavior by lithium intercalation and deintercalation, which resulted in coloration and bleaching of the film. Upon dehydration at about 450 deg. C, the hexagonal MoO{sub 3}.nH{sub 2}O was transformed into the thermodynamically stable orthorhombic phase. - Abstract: SEM photograph of typical h-MoO{sub 3}.nH{sub 2}O thin film nuclei obtained after 36 h at 40 deg. C by the LPD method. Display Omitted

  19. Photocatalysis and photoelectrochemical properties of tungsten trioxide nanostructured films.

    PubMed

    Lai, Chin Wei

    2014-01-01

    Tungsten trioxide (WO₃) possesses a small band gap energy of 2.4-2.8 eV and is responsive to both ultraviolet and visible light irradiation including strong absorption of the solar spectrum and stable physicochemical properties. Thus, controlled growth of one-dimensional (1D) WO₃ nanotubular structures with desired length, diameter, and wall thickness has gained significant interest. In the present study, 1D WO₃ nanotubes were successfully synthesized via electrochemical anodization of tungsten (W) foil in an electrolyte composed of 1 M of sodium sulphate (Na₂SO₄) and ammonium fluoride (NH₄F). The influence of NH₄F content on the formation mechanism of anodic WO₃ nanotubular structure was investigated in detail. An optimization of fluoride ions played a critical role in controlling the chemical dissolution reaction in the interface of W/WO₃. Based on the results obtained, a minimum of 0.7 wt% of NH₄F content was required for completing transformation from W foil to WO₃ nanotubular structure with an average diameter of 85 nm and length of 250 nm within 15 min of anodization time. In this case, high aspect ratio of WO₃ nanotubular structure is preferred because larger active surface area will be provided for better photocatalytic and photoelectrochemical (PEC) reactions.

  20. Mineral trioxide aggregate: a review of physical properties.

    PubMed

    Malhotra, Neeraj; Agarwal, Antara; Mala, Kundabala

    2013-02-01

    The purpose of this two-part series is to review the composition, properties, products, and clinical aspects of mineral trioxide aggregate (MTA) materials. Electronic search of scientific papers from January 1991 to May 2010 was accomplished using PubMed and MedLine search engines to include relevant scientific citations from the peer-reviewed journals published in English. MTA is a refined form of the parent compound, Portland cement (PC). It demonstrates a strong biocompatible nature owing to the high pH and its ability to form hydroxyapatite. MTA materials provide a better seal than traditional endodontic materials as observed in dye leakage, fluid filtration, protein leakage, and bacterial penetration leakage studies, and it has been recognized as a bioactive material. Currently a variety of MTA commercial products are available, including Proroot Gray MTA and White MTA both from DENTSPLY Tulsa Dental Specialties (www.DENTSPLY.com), and MTA Angelus (Angelus,www.angelus.ind.br). Although these materials are indicated for various dental uses/applications, long-term in-vivo clinical studies are still needed to claim the same. This first of this series highlights and discusses the composition, physical, and/or chemical properties of MTA. A subsequent article will offer an overview of the material aspect (commercial products) and clinical considerations for MTA materials. PMID:23627406

  1. Emissions of sulfur trioxide from coal-fired power plants.

    PubMed

    Srivastava, R K; Miller, C A; Erickson, C; Jambhekar, R

    2004-06-01

    Emissions of sulfur trioxide (SO3) are a key component of plume opacity and acid deposition. Consequently, these emissions need to be low enough to not cause opacity violations and acid deposition. Generally, a small fraction of sulfur (S) in coal is converted to SO3 in coal-fired combustion devices such as electric utility boilers. The emissions of SO3 from such a boiler depend on coal S content, combustion conditions, flue gas characteristics, and air pollution devices being used. It is well known that the catalyst used in the selective catalytic reduction (SCR) technology for nitrogen oxides control oxidizes a small fraction of sulfur dioxide in the flue gas to SO3. The extent of this oxidation depends on the catalyst formulation and SCR operating conditions. Gas-phase SO3 and sulfuric acid, on being quenched in plant equipment (e.g., air preheater and wet scrubber), result in fine acidic mist, which can cause increased plume opacity and undesirable emissions. Recently, such effects have been observed at plants firing high-S coal and equipped with SCR systems and wet scrubbers. This paper investigates the factors that affect acidic mist production in coal-fired electric utility boilers and discusses approaches for mitigating emission of this mist. PMID:15242154

  2. Reversal effect of arsenic sensitivity in human leukemia cell line K562 and K562/ADM using realgar transforming solution.

    PubMed

    Wang, Xin; Zhang, Xu; Xu, Zhiliang; Wang, Zhizeng; Yue, Xiaoxuan; Li, Hongyu

    2013-01-01

    The success of arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL) attracts a great deal of attention to researchers to explore its activity of anti-leukemia. However, ATO has unavailable effect on chronic myeloid leukemia (CML), especially multidrug resistant (MDR)-CML, unless using high concentration. Realgar (As(4)S(4)) has been employed in Chinese traditional medicine for 1500 years. Research evidences confirmed realgar has similar effect on treating with APL as ATO, but the problem of large dose and long period in the CML/MDR-CML treatment still exist. By using a microbial leaching process with Acidithiobacillus ferrooxidans, we obtained realgar transforming solution (RTS) which showed significantly higher extent in inhibiting CML cell line K562 and MDR-CML cell line K562/ADM, and then trigger apoptosis. Both K562 and K562/ADM showed arsenic-dose-dependent effect on RTS. Interestingly, the overexpression of MDR1 mRNA and P-glucoprotein (P-gp) in K562/ADM cells were down-regulated by RTS, where there are no obvious effects on ATO and realgar and arsenic can be subsequently accumulated in K562/ADM cells efficiently. The intracellular accumulation of arsenic in K562/ADM cells treated with RTS for 4 h was 2-fold and 16-folds higher than those treated with realgar or ATO. Meanwhile, Western blot analysis of AQP9, the main transporter of arsenic, was increased by RTS treatment particularly in K562/ADM. Thus, these results suggested that the effect from a certain arsenical or a variety of arsenicals in RTS might be a promising candidate both for treating CML/MDR-CML alone and as combinations with currently used anti-CML/MDR-CML drug, although arsenical forms in RTS are undefined.

  3. The embryotoxic response to maternal chromium trioxide exposure in different strains of hamsters

    SciTech Connect

    Gale, T.F.

    1982-10-01

    This paper compares the chromium trioxide-induced embryotoxic effects among one noninbred (LVG) and five inbred (CB, LHC, LSH, MHA, PD4) strains of hamsters. A single dose of chromium trioxide (8 mg/kg, iv) was injected into pregnant hamsters on the morning of gestation Day 8. Treated and control animals were killed on gestation Day 15 and studied for the types and incidence of external and internal abnormalities, as well as the frequency of resorption sites per uterus. The embryotoxic effects described in this study include significant rates of resorptions, external abnormalities, cleft palate, and hydrocephalus. The results indicate that the MHA, LSH, and LVG strains are susceptible, while the CB, LHC, and PD4 strains are resistant to chromium trioxide-induced embryotoxicity. This study was compared with prior work in which the same hamster strains were treated with either cadmium, lead, or mercury.

  4. Avulsed Immature Permanent Central Incisors Obturated With Mineral Trioxide Aggregate: A Case Report

    PubMed Central

    Al-Kahtani, Ahmed

    2013-01-01

    The endodontic management of immature permanent incisors in young children can be challenging. This case reported an avulsed immature maxillary central incisors that underwent complete endodontic obturation using mineral trioxide aggregate. A 10-year-old male who suffered a fall injury avulsed both his central incisors. The revascularization process was not possible due to patient compliance and geographic reasons. Mineral trioxide aggregate was utilized as a novel endodontic treatment. After one year post-injury, the teeth remained symptom-free, the clinical and radiographic follow-up showed evidence of healthy periodontium. How to cite this article: Al-Kahtani A. Avulsed Immature Permanent Central Incisors Obturated With Mineral Trioxide Aggregate: A Case Report. J Int Oral Health 2013; 5(3):88-96. PMID:24155609

  5. Reactions of connective tissue to amalgam, intermediate restorative material, mineral trioxide aggregate, and mineral trioxide aggregate mixed with chlorhexidine.

    PubMed

    Sumer, Mahmut; Muglali, Mehtap; Bodrumlu, Emre; Guvenc, Tolga

    2006-11-01

    The aim of this study was to histopathologically examine the biocompatibility of the high-copper amalgam, intermediate restorative material (IRM), mineral trioxide aggregate (MTA), and MTA mixed with chlorhexidine (CHX). This study was conducted to observe the rat subcutaneous connective tissue reaction to the implanted tubes filled with amalgam, IRM, MTA, and MTA mixed with CHX. The animals were sacrificed 15, 30, and 60 days after the implantation procedure. The implant sites were excised and prepared for histological evaluation. Sections of 5 to 6 microm thickness were cut by a microtome and stained with hemotoxylin eosin and examined under a light microscope. The inflammatory reactions were categorized as weak (none or few inflammatory cells < or =25 cells), moderate (>25 cells), and severe (a lot of inflammatory cells not to be counted, giant cells, and granulation tissue). Thickness of fibrous capsules measured five different areas by the digital imaging and the mean values were scored. Amalgam, IRM, and MTA mixed with CHX caused a weak inflammatory response on days 15, 30, and 60. MTA provoked an initial severe inflammatory response that subsided at the 30 and 60 day study period. A clear fibrous capsule was observed beginning from the 15 days in all of the groups. Within the limits of this study, amalgam, IRM, MTA, and MTA mixed with CHX materials were surrounded by fibrous connective tissue indicated that they were well tolerated by the tissues, therefore, MTA/CHX seemed to be biocompatible.

  6. Acute arsenic intoxication from environmental arsenic exposure

    SciTech Connect

    Franzblau, A.; Lilis, R. )

    1989-11-01

    Reports of acute arsenic poisoning arising from environmental exposure are rare. Two cases of acute arsenic intoxication resulting from ingestion of contaminated well water are described. These patients experienced a variety of problems: acute gastrointestinal symptoms, central and peripheral neurotoxicity, bone marrow suppression, hepatic toxicity, and mild mucous membrane and cutaneous changes. Although located adjacent to an abandoned mine, the well water had been tested for microorganisms only and was found to be safe. Regulations for testing of water from private wells for fitness to drink are frequently nonexistent, or only mandate biologic tests for microorganisms. Well water, particularly in areas near mining activity, should be tested for metals.

  7. Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

    PubMed Central

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

    2012-01-01

    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. PMID:22690182

  8. Classification of current anticancer immunotherapies.

    PubMed

    Galluzzi, Lorenzo; Vacchelli, Erika; Bravo-San Pedro, José-Manuel; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P; Coussens, Lisa; Dhodapkar, Madhav V; Eggermont, Alexander M; Fearon, Douglas T; Fridman, Wolf H; Fučíková, Jitka; Gabrilovich, Dmitry I; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M; Klein, Eva; Knuth, Alexander; Lewis, Claire E; Liblau, Roland; Lotze, Michael T; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J; Mittendorf, Elizabeth A; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E; Pienta, Kenneth J; Porgador, Angel; Prendergast, George C; Rabinovich, Gabriel A; Restifo, Nicholas P; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J; Speiser, Daniel E; Spisek, Radek; Srivastava, Pramod K; Talmadge, James E; Tartour, Eric; Van Der Burg, Sjoerd H; Van Den Eynde, Benoît J; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S; Whiteside, Theresa L; Wolchok, Jedd D; Zitvogel, Laurence; Zou, Weiping; Kroemer, Guido

    2014-12-30

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.

  9. Classification of current anticancer immunotherapies

    PubMed Central

    Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

    2014-01-01

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  10. Classification of current anticancer immunotherapies.

    PubMed

    Galluzzi, Lorenzo; Vacchelli, Erika; Bravo-San Pedro, José-Manuel; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P; Coussens, Lisa; Dhodapkar, Madhav V; Eggermont, Alexander M; Fearon, Douglas T; Fridman, Wolf H; Fučíková, Jitka; Gabrilovich, Dmitry I; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M; Klein, Eva; Knuth, Alexander; Lewis, Claire E; Liblau, Roland; Lotze, Michael T; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J; Mittendorf, Elizabeth A; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E; Pienta, Kenneth J; Porgador, Angel; Prendergast, George C; Rabinovich, Gabriel A; Restifo, Nicholas P; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J; Speiser, Daniel E; Spisek, Radek; Srivastava, Pramod K; Talmadge, James E; Tartour, Eric; Van Der Burg, Sjoerd H; Van Den Eynde, Benoît J; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S; Whiteside, Theresa L; Wolchok, Jedd D; Zitvogel, Laurence; Zou, Weiping; Kroemer, Guido

    2014-12-30

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  11. Dye leakage and modification of fast-setting mineral trioxide aggregate.

    PubMed

    Challenger, Hereward; Lane, Jason; Becker, Ryan; Nassiripour, Sepehr; Torabinejad, Mahmoud

    2015-02-01

    The objective of this investigation was to determine and decrease dye leakage of fast-setting mineral trioxide aggregate (FSMTA). Specimens using differing setting times or concentrations of calcium sulfate modified FSMTA were assessed for dye penetration. Based on the results, no statistical difference was found in the dye leakage of FSMTA compared with regular mineral trioxide aggregate (MTA). The addition of 10 percent calcium sulfate resulted in a statistical reduction in dye leakage compared to both unmodified FSMTA and regular MTA. PMID:25868222

  12. Arsenic and liver disease.

    PubMed

    Guha Mazumder, D N

    2001-06-01

    The hepatotoxic action of arsenic, when used as a therapeutic agent, has long been recognised. Data on liver involvement following chronic exposure to arsenic-contaminated water are scanty. The nature and degree of liver involvement are reported on the basis of hospital based studies in patients who consumed arsenic contaminated drinking water for one to 15 years. Two hundred forty-eight patients with evidence of chronic arsenic toxicity underwent clinical and laboratory examination including liver function tests and hepatitis B surface antigen (HBsAg) status. Liver biopsy was done in 69 cases; in 29 patients, liver arsenic content was estimated by neutron activation analysis. Hepatomegaly was present in 190 of 248 patients (76.6%). Non-cirrhotic portal fibrosis was the predominant lesion (91.3%) in liver histology. The maximum arsenic content in liver was 6 mg/kg (mean 1.46 [0.42], control value 0.16 [0.04]; p <0.001); it was undetected in 6 of 29 samples studied. The largest number of patients with liver disease due to chronic arsenicosis from drinking arsenic contaminated water are reported. Non-cirrhotic portal fibrosis is the predominant lesion in this population. Hepatic fibrosis has also been demonstrated due to long term arsenic toxicity in an animal model. Initial biochemical evidence of hepatic membrane damage, probably due to reduction of glutathione and antioxidant enzymes, may be seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum aminotransferases elevated at 12 months and hepatic fibrosis at 15 months.

  13. Environmental biochemistry of arsenic

    SciTech Connect

    Tamaki, S.; Frankenberger, W.T. Jr. )

    1992-01-01

    Microorganisms are involved in the redistribution and global cycling of arsenic. Arsenic can accumulate and can be subject to various biotransformations including reduction, oxidation, and methylation. Bacterial methylation of inorganic arsenic is coupled to the methane biosynthetic pathway in methanogenic bacteria under anaerobic conditions and may be a mechanism for arsenic detoxification. The pathway proceeds by reduction of arsenate to arsenite followed by methylation to dimethylarsine. Fungi are also able to transform inorganic and organic arsenic compounds into volatile methylarsines. The pathway proceeds aerobically by arsenate reduction to arsenite followed by several methylation steps producing trimethylarsine. Volatile arsine gases are very toxic to mammals because they destroy red blood cells (LD50 in rats; 3.0 mg kg-1). Further studies are needed on dimethylarsine and trimethylarsine toxicity tests through inhalation of target animals. Marine algae transform arsenate into non-volatile methylated arsenic compounds (methanearsonic and dimethylarsinic acids) in seawater. This is considered to be a beneficial step not only to the primary producers, but also to the higher trophic levels, since non-volatile methylated arsenic is much less toxic to marine invertebrates. Freshwater algae like marine algae synthesize lipid-soluble arsenic compounds and do not produce volatile methylarsines. Aquatic plants also synthesize similar lipid-soluble arsenic compounds. In terrestrial plants, arsenate is preferentially taken up 3 to 4 times the rate of arsenite. In the presence of phosphate, arsenate uptake is inhibited while in the presence of arsenate, phosphate uptake is only slightly inhibited. There is a competitive interaction between arsenate and phosphate for the same uptake system in terrestrial plants.

  14. 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. PMID:12696647

  15. Chronic Arsenic poisoning.

    PubMed

    Ahsan, Tasnim; Zehra, Kaneez; Munshi, Alia; Ahsan, Samiah

    2009-02-01

    Chronic Arsenic Toxicity may have varied clinical presentations ranging from non-cancerous manifestations to malignancy of skin and different internal organs. Dermal lesions such as hyper pigmentation and hyperkeratosis, predominantly over palms and soles are diagnostic of Chronic Arsenicosis. We report two cases from a family living in Sukkur who presented with classical skin lesions described in Chronic Arsenicosis. The urine, nail and hair samples of these patients contained markedly elevated levels of arsenic. Also the water samples from their household and the neighbouring households were found to have alarming levels of inorganic Arsenic.

  16. Chitin and chitosan as multipurpose natural polymers for groundwater arsenic removal and AS2O3 delivery in tumor therapy.

    PubMed

    Da Sacco, Letizia; Masotti, Andrea

    2010-01-01

    Chitin and chitosan are natural polysaccharide polymers. These polymers have been used in several agricultural, food protection and nutraceutical applications. Moreover, chitin and chitosan have been also used in biomedical and biotechnological applications as drug delivery systems or in pharmaceutical formulations. So far, there are only few studies dealing with arsenic (As) removal from groundwater using chitin or chitosan and no evidence of the use of these natural polymers for arsenic trioxide (As(2)O(3)) delivery in tumor therapy. Here we suggest that chitin and/or chitosan might have the right properties to be employed as efficient polymers for such applications. Besides, nanotechnology offers suitable tools for the fabrication of novel nanostructured materials of natural origin. Since different nanostructured materials have already been employed successfully in various multidisciplinary fields, we expect that the integration of nanotechnology and natural polymer chemistry will further lead to innovative applications for environment and medicine.

  17. Anticancer agents from marine sponges.

    PubMed

    Ye, Jianjun; Zhou, Feng; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine sponges are currently one of the richest sources of anticancer active compounds found in the marine ecosystems. More than 5300 different known metabolites are from sponges and their associated microorganisms. To survive in the complicated marine environment, most of the sponge species have evolved chemical means to defend against predation. Such chemical adaptation produces many biologically active secondary metabolites including anticancer agents. This review highlights novel secondary metabolites in sponges which inhibited diverse cancer species in the recent 5 years. These natural products of marine sponges are categorized based on various chemical characteristics.

  18. 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...

  19. Contribution to the photometric determination of small amounts of boron trioxide in glasses

    NASA Technical Reports Server (NTRS)

    Markova, D.

    1985-01-01

    The photometric determination for boron trioxide is described in amounts of 0-75 micrograms B2O3 with an azomethin H reagent. The yellow colored complex which occurs in a medium held at a pH of 4.5 was measured in light of a wavelength of 415 nm.

  20. A note on the biological activity of the noble gas compound xenon trioxide.

    NASA Technical Reports Server (NTRS)

    Siegel, S. M.; Smith, C. W.

    1972-01-01

    Comparison of xenon trioxide for toxicity in the few common oxidants using three bioassays. On a molar basis XeO3 and HOCl were similar, but XeO3 was less active than expected when comparisons were based on normality.

  1. 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

  2. Anticancer activity of Amauroderma rude.

    PubMed

    Jiao, Chunwei; Xie, Yi-Zhen; Yang, Xiangling; Li, Haoran; Li, Xiang-Min; Pan, Hong-Hui; Cai, Mian-Hua; Zhong, Hua-Mei; Yang, Burton B

    2013-01-01

    More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approximately 30 species widespread throughout the tropical areas. Since the biological function of Amauroderma rude is unknown, we examined its anti-cancer effect on breast carcinoma cell lines. We compared the anti-cancer activity of Amauroderma rude and Ganoderma lucidum, the most well-known medicinal mushrooms with anti-cancer activity and found that Amauroderma rude had significantly higher activity in killing cancer cells than Ganoderma lucidum. We then examined the effect of Amauroderma rude on breast cancer cells and found that at low concentrations, Amauroderma rude could inhibit cancer cell survival and induce apoptosis. Treated cancer cells also formed fewer and smaller colonies than the untreated cells. When nude mice bearing tumors were injected with Amauroderma rude extract, the tumors grew at a slower rate than the control. Examination of these tumors revealed extensive cell death, decreased proliferation rate as stained by Ki67, and increased apoptosis as stained by TUNEL. Suppression of c-myc expression appeared to be associated with these effects. Taken together, Amauroderma rude represented a powerful medicinal mushroom with anti-cancer activities. PMID:23840494

  3. Anticancer Activity of Amauroderma rude

    PubMed Central

    Yang, Xiangling; Li, Haoran; Li, Xiang-Min; Pan, Hong-Hui; Cai, Mian-Hua; Zhong, Hua-Mei; Yang, Burton B.

    2013-01-01

    More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approximately 30 species widespread throughout the tropical areas. Since the biological function of Amauroderma rude is unknown, we examined its anti-cancer effect on breast carcinoma cell lines. We compared the anti-cancer activity of Amauroderma rude and Ganoderma lucidum, the most well-known medicinal mushrooms with anti-cancer activity and found that Amauroderma rude had significantly higher activity in killing cancer cells than Ganoderma lucidum. We then examined the effect of Amauroderma rude on breast cancer cells and found that at low concentrations, Amauroderma rude could inhibit cancer cell survival and induce apoptosis. Treated cancer cells also formed fewer and smaller colonies than the untreated cells. When nude mice bearing tumors were injected with Amauroderma rude extract, the tumors grew at a slower rate than the control. Examination of these tumors revealed extensive cell death, decreased proliferation rate as stained by Ki67, and increased apoptosis as stained by TUNEL. Suppression of c-myc expression appeared to be associated with these effects. Taken together, Amauroderma rude represented a powerful medicinal mushroom with anti-cancer activities. PMID:23840494

  4. 40 CFR 61.180 - Applicability and designation of sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade...

  5. 40 CFR 61.180 - Applicability and designation of sources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade...

  6. 40 CFR 61.180 - Applicability and designation of sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade...

  7. 40 CFR 61.180 - Applicability and designation of sources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade...

  8. 40 CFR 61.180 - Applicability and designation of sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade...

  9. 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...

  10. 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...

  11. 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,...

  12. Sources and circulation of water and arsenic in the Giant Mine, Yellowknife, NWT, Canada.

    PubMed

    Clark, Ian D; Raven, Kenneth G

    2004-06-01

    Recovery of gold from arsenopyrite-hosted ore in the Giant Mine camp, Yellowknife, NWT, Canada, has left a legacy of arsenic contamination that poses challenges for mine closure planning. Seepage from underground chambers storing some 237,000 tonnes of arsenic trioxide dust, has As concentrations exceeding 4000 ppm. Other potential sources and sinks of As also exist. Sources and movement of water and arsenic are traced using the isotopes of water and sulphate. Mine waters (16 ppm As; AsV/AsIII approximately 150) are a mixture of two principal water sources--locally recharged, low As groundwaters (0.5 ppm As) and Great Slave Lake (GSL; 0.004 ppm As) water, formerly used in ore processing and discharged to the northwest tailings impoundment (NWTP). Mass balance with delta18O shows that recirculation of NWTP water to the underground through faults and unsealed drillholes contributes about 60% of the mine water. Sulphate serves to trace direct infiltration to the As2O3 chambers. Sulphate in local, low As groundwaters (0.3-0.6 ppm As; delta34SSO4 approximately 4% and delta18OSO4 approximately -10%) originates from low-temperature aqueous oxidation of sulphide-rich waste rock. The high As waters gain a component of 18O-enriched sulphate derived from roaster gases (delta18OSO4) = + 3.5%), consistent with their arsenic source from the As2O3 chambers. High arsenic in NWTP water (approximately 8 ppm As; delta18OSO4 = -2%) derived from mine water, is attenuated to close to 1 ppm during infiltration back to the underground, probably by oxidation and sorption by ferrihydrite.

  13. Arsenic in cancer treatment: challenges for application of realgar nanoparticles (a minireview).

    PubMed

    Baláž, Peter; Sedlák, Ján

    2010-06-01

    While intensive efforts have been made for the treatment of cancer, this disease is still the second leading cause of death in many countries. Metastatic breast cancer, late-stage colon cancer, malignant melanoma, multiple myeloma, and other forms of cancer are still essentially incurable in most cases. Recent advances in genomic technologies have permitted the simultaneous evaluation of DNA sequence-based alterations together with copy number gains and losses. The requirement for a multi-targeting approach is the common theme that emerges from these studies. Therefore, the combination of new targeted biological and cytotoxic agents is currently under investigation in multimodal treatment regimens. Similarly, a combinational principle is applied in traditional Chinese medicine, as formulas consist of several types of medicinal herbs or minerals, in which one represents the principal component, and the others serve as adjuvant ones that assist the effects, or facilitate the delivery, of the principal component. In Western medicine, approximately 60 different arsenic preparations have been developed and used in pharmacological history. In traditional Chinese medicines, different forms of mineral arsenicals (orpiment-As(2)S(3), realgar-As(4)S(4), and arsenolite-arsenic trioxide, As(2)O(3)) are used, and realgar alone is included in 22 oral remedies that are recognized by the Chinese Pharmacopeia Committee (2005). It is known that a significant portion of some forms of mineral arsenicals is poorly absorbed into the body, and would be unavailable to cause systemic damage. This review primary focuses on the application of arsenic sulfide (realgar) for treatment of various forms of cancer in vitro and in vivo. PMID:22069650

  14. Arsenic in Cancer Treatment: Challenges for Application of Realgar Nanoparticles (A Minireview)

    PubMed Central

    Baláž, Peter; Sedlák, Ján

    2010-01-01

    While intensive efforts have been made for the treatment of cancer, this disease is still the second leading cause of death in many countries. Metastatic breast cancer, late-stage colon cancer, malignant melanoma, multiple myeloma, and other forms of cancer are still essentially incurable in most cases. Recent advances in genomic technologies have permitted the simultaneous evaluation of DNA sequence-based alterations together with copy number gains and losses. The requirement for a multi-targeting approach is the common theme that emerges from these studies. Therefore, the combination of new targeted biological and cytotoxic agents is currently under investigation in multimodal treatment regimens. Similarly, a combinational principle is applied in traditional Chinese medicine, as formulas consist of several types of medicinal herbs or minerals, in which one represents the principal component, and the others serve as adjuvant ones that assist the effects, or facilitate the delivery, of the principal component. In Western medicine, approximately 60 different arsenic preparations have been developed and used in pharmacological history. In traditional Chinese medicines, different forms of mineral arsenicals (orpiment—As2S3, realgar—As4S4, and arsenolite—arsenic trioxide, As2O3) are used, and realgar alone is included in 22 oral remedies that are recognized by the Chinese Pharmacopeia Committee (2005). It is known that a significant portion of some forms of mineral arsenicals is poorly absorbed into the body, and would be unavailable to cause systemic damage. This review primary focuses on the application of arsenic sulfide (realgar) for treatment of various forms of cancer in vitro and in vivo. PMID:22069650

  15. Relationship of expression of aquaglyceroporin 9 with arsenic uptake and sensitivity in leukemia cells.

    PubMed

    Leung, Jordy; Pang, Annie; Yuen, Wai-Hung; Kwong, Yok-Lam; Tse, Eric W C

    2007-01-15

    Arsenic trioxide (As2O3) is highly efficacious in acute promyelocytic leukemia (APL). Aquaglyceroporin 9 (AQP9) is a transmembrane protein that may be involved in arsenic uptake. In 10 of 11 myeloid and lymphoid leukemia lines, quantitative polymerase chain reaction (Q-PCR) and Western blotting showed that AQP9 expression correlated positively with As2O3-induced cytotoxicity. As a proof-of-principle, transfection of EGFP-tagged AQP9 to the hepatoma line Hep3B, not expressing AQP9 and As2O3 insensitive, led to membrane AQP9 expression and increased As2O3-induced cytotoxicity. Similarly, the chronic myeloid leukemia line K562 expressed low levels of AQP9 and was As2O3 insensitive. The K562(EGFP-AQP9) transfectant accumulated significantly higher levels of intracellular arsenic than control K562(EGFP) when incubated with As2O3, resulting in significantly increased As2O3-induced cytotoxicity. Pretreatment of the myeloid leukemia line HL-60 with all-trans retinoic acid (ATRA) up-regulated AQP9, leading to a significantly increased arsenic uptake and As2O3-induced cytotoxicity on incubation with As2O3, which might explain the synergism between ATRA and As2O3. Therefore, AQP9 controlled arsenic transport and might determine As2O3 sensitivity. Q-PCR showed that primary APL cells expressed AQP9 significantly (2-3 logs) higher than other acute myeloid leukemias (AMLs), which might explain their exquisite As2O3 sensitivity. However, APL and AML with maturation expressed comparable AQP9 levels, suggesting that AQP9 expression was related to granulocytic maturation.

  16. Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats

    PubMed Central

    Patlolla, Anita K.; Todorov, Todor I.; Tchounwou, Paul B.; van der Voet, Gijsbert; Centeno, Jose A.

    2012-01-01

    Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg bw of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p<0.05) the activities of plasma alanine aminotransferase-glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p<0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels. PMID:23175155

  17. 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

  18. The Role of Oxidative Stress in Gastrointestinal Tract Tissues Induced by Arsenic Toxicity in Cocks.

    PubMed

    Guo, Ying; Zhao, Panpan; Guo, Guangyang; Hu, Zhibo; Tian, Li; Zhang, Kexin; Zhang, Wen; Xing, Mingwei

    2015-12-01

    Arsenic (As) is a widely distributed trace element which is known to be associated with numerous adverse effects on human beings and animals. Arsenic trioxide (As2O3) is an inorganic arsenical-containing toxic compound. The effect of excessive amounts of As2O3 exposure on gastrointestinal tract tissue damage in cocks is still unknown. This study was conducted to investigate the effect of As2O3 exposure on gastrointestinal tract tissue damage in cocks. In total, 72 1-day-old male Hyline cocks were randomly divided into four groups and fed either a commercial diet or an As2O3 supplement diet containing 7.5, 15, and 30 mg/kg As2O3. The experiment lasted for 90 days and gastrointestinal tract tissue samples (gizzard, glandular stomach, duodenum, jejunum, ileum, cecum, and rectum) were collected at 30, 60, and 90 days. Catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) activities; malondialdehyde (MDA) contents; and hydroxyl radical (OH·)-mediated inhibition were examined. Furthermore, the results demonstrated that MDA content in the gastrointestinal tract was increased, while the activities of CAT, GSH, and GSH-Px and the ability to resist OH· was decreased in the As2O3 treatment groups. Extensive damage was observed in the gastrointestinal tract. These findings indicated that As2O3 exposure caused oxidative damage in the gastrointestinal tract of cocks due to alterations in antioxidant enzyme activities and elevation of free radicals.

  19. [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.

  20. 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.

  1. Chronic arsenic poisoning.

    PubMed

    Hall, Alan H

    2002-03-10

    Symptomatic arsenic poisoning is not often seen in occupational exposure settings. Attempted homicide and deliberate long-term poisoning have resulted in chronic toxicity. Skin pigmentation changes, palmar and plantar hyperkeratoses, gastrointestinal symptoms, anemia, and liver disease are common. Noncirrhotic portal hypertension with bleeding esophageal varices, splenomegaly, and hypersplenism may occur. A metallic taste, gastrointestinal disturbances, and Mee's lines may be seen. Bone marrow depression is common. 'Blackfoot disease' has been associated with arsenic-contaminated drinking water in Taiwan; Raynaud's phenomenon and acrocyanosis also may occur. Large numbers of persons in areas of India, Pakistan, and several other countries have been chronically poisoned from naturally occurring arsenic in ground water. Toxic delirium and encephalopathy can be present. CCA-treated wood (chromated copper arsenate) is not a health risk unless burned in fireplaces or woodstoves. Peripheral neuropathy may also occur. Workplace exposure or chronic ingestion of arsenic-contaminated water or arsenical medications is associated with development of skin, lung, and other cancers. Treatment may incklude the use of chelating agents such as dimercaprol (BAL), dimercaptosuccinic acid (DMSA), and dimercaptopanesulfonic acid (DMPS).

  2. Anticancer Molecular Mechanisms of Resveratrol

    PubMed Central

    Varoni, Elena M.; Lo Faro, Alfredo Fabrizio; Sharifi-Rad, Javad; Iriti, Marcello

    2016-01-01

    Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment. PMID:27148534

  3. Methylated arsenic metabolites bind to PML protein but do not induce cellular differentiation and PML-RARα protein degradation.

    PubMed

    Wang, Qian Qian; Zhou, Xin Yi; Zhang, Yan Fang; Bu, Na; Zhou, Jin; Cao, Feng Lin; Naranmandura, Hua

    2015-09-22

    Arsenic trioxide (As2O3) is one of the most effective therapeutic agents used for patients with acute promyelocytic leukemia (APL). The probable explanation for As2O3-induced cell differentiation is the direct targeting of PML-RARα oncoprotein by As2O3, which results in initiation of PML-RARα degradation. However, after injection, As2O3 is rapidly methylated in body to different intermediate metabolites such as trivalent monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), therefore, it remains unknown that which arsenic specie is actually responsible for the therapeutic effects against APL. Here we have shown the role of As2O3 (as iAs(III)) and its intermediate metabolites (i.e., MMA(III)/DMA(III)) in NB4 cells. Inorganic iAs(III) predominantly showed induction of cell differentiation, while MMA(III) and DMA(III) specifically showed to induce mitochondria and endoplasmic reticulum-mediated apoptosis, respectively. On the other hand, in contrast to iAs(III), MMA(III) showed stronger binding affinity for ring domain of PML recombinant protein, however, could not induce PML protein SUMOylation and ubiquitin/proteasome degradation. In summary, our results suggest that the binding of arsenicals to the ring domain of PML proteins is not associated with the degradation of PML-RARα fusion protein. Moreover, methylated arsenicals can efficiently lead to cellular apoptosis, however, they are incapable of inducing NB4 cell differentiation. PMID:26213848

  4. Protective effect of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic toxicity in rats induced by inorganic arsenic.

    PubMed

    Jiang, Yanhua; Wang, Lianzhu; Yao, Lin; Liu, Zhantao; Gao, Hua

    2013-09-01

    Arsenic, a potent environmental toxic agent, causes various hazardous effects on human health. This study was performed to evaluate the protective effects of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic stress of rats induced by arsenic trioxide (As2O3). The co-treatment of marine algae could slightly increase the growth rates of body weights compared to the As2O3-treated group. The marine algae application restored liver and renal function by preventing the increment in the activities of alanine transaminase and alkaline phosphatase, and the levels of total protein, blood urea nitrogen, and creatinine. The increase in the contents of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and decrease in the contents of high density lipoprotein cholesterol were observed in algae co-treated groups which indicated that marine algae could reverse the abnormal lipid metabolisms induced by arsenic. Moreover, these algae could protect the rats from lipid peroxidation by restoring the depletion of superoxide dismutase and glutathione peroxidase activities and sulfhydryl group contents, and lowering the enhanced malondialdehyde contents. Therefore, evidences indicate that L. japonica and P. haitanensis can serve as an effective regimen for treating arsenic poisoning.

  5. Protective effect of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic toxicity in rats induced by inorganic arsenic.

    PubMed

    Jiang, Yanhua; Wang, Lianzhu; Yao, Lin; Liu, Zhantao; Gao, Hua

    2013-09-01

    Arsenic, a potent environmental toxic agent, causes various hazardous effects on human health. This study was performed to evaluate the protective effects of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic stress of rats induced by arsenic trioxide (As2O3). The co-treatment of marine algae could slightly increase the growth rates of body weights compared to the As2O3-treated group. The marine algae application restored liver and renal function by preventing the increment in the activities of alanine transaminase and alkaline phosphatase, and the levels of total protein, blood urea nitrogen, and creatinine. The increase in the contents of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and decrease in the contents of high density lipoprotein cholesterol were observed in algae co-treated groups which indicated that marine algae could reverse the abnormal lipid metabolisms induced by arsenic. Moreover, these algae could protect the rats from lipid peroxidation by restoring the depletion of superoxide dismutase and glutathione peroxidase activities and sulfhydryl group contents, and lowering the enhanced malondialdehyde contents. Therefore, evidences indicate that L. japonica and P. haitanensis can serve as an effective regimen for treating arsenic poisoning. PMID:23842700

  6. Inorganic arsenic toxicosis in cattle.

    PubMed

    Riviere, J E; Boosinger, T R; Everson, R J

    1981-03-01

    In 4 occurrences of arsenic poisoning in cattle, the principal clinical sign was acute hemorrhagic diarrhea attributable to hemorrhagic gastroenteritis. Arsenic concentrations in the liver, kidney and rumen contents varied. In one occurrence, arsenic in the hair of affected survivors was assayed at 0.8-3.40 ppm, vs 0.09-0.10 ppm in randomly selected control samples of hair. Sudden death was the only clinical sign in another occurrence in which gastric contents contained arsenic at 671 ppm. In another occurrence, arsenic poisoning caused lesions similar to those of salmonellosis.

  7. Mechanisms Pertaining to Arsenic Toxicity

    PubMed Central

    Singh, Amrit Pal; Goel, Rajesh Kumar; Kaur, Tajpreet

    2011-01-01

    Arsenic is an environmental pollutant and its contamination in the drinking water is considered as a serious worldwide environmental health threat. The chronic arsenic exposure is a cause of immense health distress as it accounts for the increased risk of various disorders such as cardiovascular abnormalities, diabetes mellitus, neurotoxicity, and nephrotoxicity. In addition, the exposure to arsenic has been suggested to affect the liver function and to induce hepatotoxicity. Moreover, few studies demonstrated the induction of carcinogenicity especially cancer of the skin, bladder, and lungs after the chronic exposure to arsenic. The present review addresses diverse mechanisms involved in the pathogenesis of arsenic-induced toxicity and end-organ damage. PMID:21976811

  8. High resolution spectroscopy of sulfur trioxide and carbon suboxide

    NASA Astrophysics Data System (ADS)

    Masiello, Tony

    High resolution spectroscopy was used to study the properties of two simple polyatomic molecules, sulfur trioxide, SO3, and carbon suboxide, C3O2. The fundamental modes and several hot bands of the 18O isotopic forms of SO3 (32S18O 3 and 34S18O3) have been investigated using both infrared spectroscopy and coherent anti-Stokes Raman scattering spectroscopy (CARS). The Raman-active symmetric stretching mode, nu 1, shows complex Q-branch patterns due to indirect Coriolis couplings, l-resonances, and Fermi resonances with infrared inaccessible nu2, nu4 combination/overtone levels. 18O isotopic substitution changes the character of these interactions in such a way that their effect on the nu1 CARS spectrum is unique among the different isotopomers studied. Accurate rovibrational constants are determined for all of the mixed states for the first time, leading to deperturbed values for the nu1 band origin of 1004.661(24) and 1004.693(23) for 34S18O 3 and 32S18O3 respectively. The strong Coriolis coupling is very noticeable in these species due to the close proximity of the nu2 and nu4 fundamental vibrations. The effect that this and other interaction terms have on the nu1 CARS spectrum of 34S18O3 is examined by selectively turning off the coupling between the hot bands. A global force field analysis was performed with the fundamental frequency values of all of the isotopomers studied that revealed a counterintuitive trend in the bond lengths between sulfur oxide species. In addition, band center frequencies for all the mixed 16O-18O isotopic species are computed. High-resolution CARS Spectroscopy was also used to study the nu 1 symmetric CO stretching mode of the quasi-linear molecule carbon suboxide, C3O2. Q-branches are seen that originate from the ground state and from thermally-populated levels of the unusually low frequency nu7 bending mode. The intensity variation of these on cooling to about 110 K in a jet expansion requires reversal of the order of assignment

  9. Arsenical peripheral neuropathy.

    PubMed

    Mathew, Liberty; Vale, Allister; Adcock, Jane E

    2010-02-01

    A 49-year-old white man returned urgently to the UK after spending 3 months in Goa. He had a several week history of vomiting, weight loss, a widespread desquamating skin rash, and symptoms and signs of a progressive painful sensorimotor neuropathy. He had a mild normocytic anaemia and lymphopenia. Nerve conduction studies revealed a severe predominantly axonal large fibre sensorimotor neuropathy, confirmed on subsequent sural nerve biopsy. Once he had left Goa most of his symptoms started to rapidly settle although the neuropathic symptoms remained severe. Arsenic poisoning was suspected. A spot urine arsenic concentration was 300 microg/l, confirming the diagnosis. He was treated with chelation therapy. Deliberate arsenic poisoning was highly likely.

  10. Arsenic Speciation of Terrestrial Invertebrates

    SciTech Connect

    Moriarty, M.M.; Koch, I.; Gordon, R.A.; Reimer, K.J. ); )

    2009-07-01

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

  11. Environmental source of arsenic exposure.

    PubMed

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-09-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

  12. Environmental Source of Arsenic Exposure

    PubMed Central

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-01-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made. PMID:25284196

  13. Environmental source of arsenic exposure.

    PubMed

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-09-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made. PMID:25284196

  14. Arsenic levels in Oregon waters.

    PubMed

    Stoner, J C; Whanger, P D; Weswig, P H

    1977-08-01

    The arsenic content of well water in certain areas of Oregon can range up to 30 to 40 times the U.S.P.H.S. Drinking Water Standard of 1962, where concentrations in excess of 50 ppb are grounds for rejection. The elevated arsenic levels in water are postulated to be due to volcanic deposits. Wells in central Lane County, Oregon, that are known to contain arsenic rich water are in an area underlain by a particular group of sedimentary and volcanic rocks, which geologists have named the Fischer formation. The arsenic levels in water from wells ranged from no detectable amounts to 2,000 ppb. In general the deeper wells contained higher arsenic water. The high arsenic waters are characterized by the small amounts of calcium and magnesium in relation to that of sodium, a high content of boron, and a high pH. Water from some hot springs in other areas of Oregon was found to range as high as 900 ppb arsenic. Arsenic blood levels ranged from 32 ppb for people living in areas where water is low in arsenic to 250 ppb for those living in areas where water is known to contain high levels of arsenic. Some health problems associated with consumption of arsenic-rich water are discussed.

  15. ARSENIC SPECIATION ANALYSIS IN HUMAN SALIVA

    EPA Science Inventory

    Background: Determination of arsenic species in human saliva is potentially useful for biomonitoring of human exposure to arsenic and for studying arsenic metabolism. However, there is no report on the speciation analysis of arsenic in saliva. Methods: Arsenic species in saliva ...

  16. ELUCIDATING THE PATHWAY FOR ARSENIC METHYLATION

    EPA Science Inventory

    Enzymatically-catalyzed methylation of arsenic is part of a metabolic pathway that converts inorganic arsenic into methylated products. Hence, in humans chronically exposed to inorganic arsenic, methyl and dimethyl arsenic account for most of the arsenic that is excreted in the ...

  17. Arsenic removal by coagulation

    SciTech Connect

    Scott, K.N.; Green, J.F.; Do, H.D.; McLean, S.J.

    1995-04-01

    This study evaluated the removal of naturally occurring arsenic in a full-scale (106-mgd) conventional treatment plant. When the source water was treated with 3--10 mg/L of ferric chloride or 6, 10, or 20 mg/L of alum, arsenic removal was 81--96% (ferric chloride) and 23--71% (alum). Metal concentrations in the sludge produced during this study were below the state`s current hazardous waste levels at all coagulant dosages. No operational difficulties were encountered.

  18. Arsenic doped zinc oxide

    SciTech Connect

    Volbers, N.; Lautenschlaeger, S.; Leichtweiss, T.; Laufer, A.; Graubner, S.; Meyer, B. K.; Potzger, K.; Zhou Shengqiang

    2008-06-15

    As-doping of zinc oxide has been approached by ion implantation and chemical vapor deposition. The effect of thermal annealing on the implanted samples has been investigated by using secondary ion mass spectrometry and Rutherford backscattering/channeling geometry. The crystal damage, the distribution of the arsenic, the diffusion of impurities, and the formation of secondary phases is discussed. For the thin films grown by vapor deposition, the composition has been determined with regard to the growth parameters. The bonding state of arsenic was investigated for both series of samples using x-ray photoelectron spectroscopy.

  19. Biochemistry of arsenic detoxification.

    PubMed

    Rosen, Barry P

    2002-10-01

    All living organisms have systems for arsenic detoxification. The common themes are (a) uptake of As(V) in the form of arsenate by phosphate transporters, (b) uptake of As(III) in the form of arsenite by aquaglyceroporins, (c) reduction of As(V) to As(III) by arsenate reductases, and (d) extrusion or sequestration of As(III). While the overall schemes for arsenic resistance are similar in prokaryotes and eukaryotes, some of the specific proteins are the products of separate evolutionary pathways.

  20. Arsenic and Selenium

    NASA Astrophysics Data System (ADS)

    Plant, J. A.; Kinniburgh, D. G.; Smedley, P. L.; Fordyce, F. M.; Klinck, B. A.

    2003-12-01

    Arsenic (As) and selenium (Se) have become increasingly important in environmental geochemistry because of their significance to human health. Their concentrations vary markedly in the environment, partly in relation to geology and partly as a result of human activity. Some of the contamination evident today probably dates back to the first settled civilizations which used metals.Arsenic is in group 15 of the periodic table (Table 1) and is usually described as a metalloid. It has only one stable isotope, 75As. It can exist in the -III, -I, 0, III, and V oxidation states (Table 2).

  1. ARSENIC REMOVAL TREATMENT OPTIONS FOR SINGLE FAMILY HOMES

    EPA Science Inventory

    The presentation provides information on POU and POE arsenic removal drinking water treatment systems. The presentation provides information on the arsenic rule, arsenic chemistry and arsenic treatment. The arsenic treatment options proposed for POU and POE treatment consist prim...

  2. Efficacy of arsenic filtration by Kanchan arsenic filter in Nepal.

    PubMed

    Singh, Anjana; Smith, Linda S; Shrestha, Shreekrishna; Maden, Narendra

    2014-09-01

    Groundwater arsenic contamination has caused a significant public health burden in lowland regions of Nepal. For arsenic mitigation purposes, the Kanchan Arsenic Filter (KAF) was developed and validated for use in 2003 after pilot studies showed its effectiveness in removing arsenic. However, its efficacy in field conditions operating for a long period has been scarcely observed. In this study, we observe the efficacy of KAFs running over 6 months in highly arsenic-affected households in Nawalparasi district. We assessed pair-wise arsenic concentrations of 62 randomly selected household tubewells before filtration and after filtration via KAFs. Of 62 tubewells, 41 had influent arsenic concentration exceeding the Nepal drinking water quality standard value (50 μg/L). Of the 41 tubewells having unsafe arsenic levels, KAFs reduced arsenic concentration to the safe level for only 22 tubewells, an efficacy of 54%. In conclusion, we did not find significantly high efficacy of KAFs in reducing unsafe influent arsenic level to the safe level under the in situ field conditions.

  3. Efficacy of arsenic filtration by Kanchan arsenic filter in Nepal.

    PubMed

    Singh, Anjana; Smith, Linda S; Shrestha, Shreekrishna; Maden, Narendra

    2014-09-01

    Groundwater arsenic contamination has caused a significant public health burden in lowland regions of Nepal. For arsenic mitigation purposes, the Kanchan Arsenic Filter (KAF) was developed and validated for use in 2003 after pilot studies showed its effectiveness in removing arsenic. However, its efficacy in field conditions operating for a long period has been scarcely observed. In this study, we observe the efficacy of KAFs running over 6 months in highly arsenic-affected households in Nawalparasi district. We assessed pair-wise arsenic concentrations of 62 randomly selected household tubewells before filtration and after filtration via KAFs. Of 62 tubewells, 41 had influent arsenic concentration exceeding the Nepal drinking water quality standard value (50 μg/L). Of the 41 tubewells having unsafe arsenic levels, KAFs reduced arsenic concentration to the safe level for only 22 tubewells, an efficacy of 54%. In conclusion, we did not find significantly high efficacy of KAFs in reducing unsafe influent arsenic level to the safe level under the in situ field conditions. PMID:25252363

  4. A Meta-Analysis of Arsenic Trioxide Combined with Transcatheter Arterial Chemoembolization for Treatment of Primary Hepatic Carcinoma

    PubMed Central

    Chen, Liguo; Chen, Ruixue

    2016-01-01

    Primary hepatic carcinoma (PHC) is one of the most common malignant tumours in the world. More and more research has shown that As2O3 combined with TACE has a good curative effect in treating PHC. The objectives of this study were to evaluate the therapeutic efficacy and safety of As2O3 combined with TACE in treating PHC. The CNKI, VIP, Wanfang, PubMed, and Cochrane databases were searched from their inception until December 2015. Randomized controlled trials (RCTs) comparing As2O3 combined with TACE versus TACE alone in treating PHC were identified. Stata SE 12.0 was used for data analysis. 17 RCTs with 1055 patients were included. Meta-analysis showed that, compared with TACE alone, As2O3 combined with TACE showed significant effects in improving the clinical efficacy rate (P < 0.01), decreasing the value of alpha-fetoprotein (P < 0.01), increasing the one-year survival rate (P < 0.01), and improving the quality of life of PHC patients (P < 0.01). Fifteen studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, As2O3 combined with TACE therapy appears to be potentially effective in treating PHC and is generally safe. However, further studies with rigorous designs trials and multiregional cooperation trials are needed. PMID:27382405

  5. Summary of the Preliminary Analysis of Savannah River Depleted Uranium Trioxide

    SciTech Connect

    NSTec Environmental Management

    2010-10-13

    This report summarizes a preliminary special analysis of the Savannah River Depleted Uranium Trioxide waste stream (SVRSURANIUM03, Revision 2). The analysis is considered preliminary because a final waste profile has not been submitted for review. The special analysis is performed to determine the acceptability of the waste stream for shallow land burial at the Area 5 Radioactive Waste Management Site (RWMS) at the Nevada National Security Site (NNSS). The Savannah River Depleted Uranium Trioxide waste stream requires a special analysis because the waste stream’s sum of fractions exceeds one. The 99Tc activity concentration is 98 percent of the NNSS Waste Acceptance Criteria and the largest single contributor to the sum of fractions.

  6. Mechanism for forming hydrogen chloride and sodium sulfate from sulfur trioxide, water, and sodium chloride

    NASA Technical Reports Server (NTRS)

    Anderson, A. B.

    1984-01-01

    A molecular orbital study of sodium sulfate and hydrogen chloride formation from sulfur trioxide, water, and sodium chloride shows no activation barrier, in agreement with recent experimental work of Kohl, Fielder, and Stearns. Two overall steps are found for the process. First, gas-phase water reacts with sulfur trioxide along a pathway involving a linear O-H-O transition state yielding closely associated hydroxyl and bisulfite which rearrange to become a hydrogen sulfate molecule. Then the hydrogen sulfate molecule transfers a hydrogen atom to a surface chloride in solid sodium chloride while an electron and a sodium cation simultaneously transfer to yield sodium bisulfate and gas-phase hydrogen chloride. This process repeats. Both of these steps represent well-known reactions for which mechanisms have not been previously determined.

  7. Arsenic and diabetes: current perspectives.

    PubMed

    Huang, Chun Fa; Chen, Ya Wen; Yang, Ching Yao; Tsai, Keh Sung; Yang, Rong Sen; Liu, Shing Hwa

    2011-09-01

    Arsenic is a naturally occurring toxic metalloid of global concern. Many studies have indicated a dose-response relationship between accumulative arsenic exposure and the prevalence of diabetes mellitus (DM) in arseniasis-endemic areas in Taiwan and Bangladesh, where arsenic exposure occurs through drinking water. Epidemiological researches have suggested that the characteristics of arsenic-induced DM observed in arseniasis-endemic areas in Taiwan and Mexico are similar to those of non-insulin-dependent DM (Type 2 DM). These studies analyzed the association between high and chronic exposure to inorganic arsenic in drinking water and the development of DM, but the effect of exposure to low to moderate levels of inorganic arsenic on the risk of DM is unclear. Navas-Acien et al. recently proposed that a positive association existed between total urine arsenic and the prevalence of Type 2 DM in people exposed to low to moderate levels of arsenic. However, the diabetogenic role played by arsenic is still debated upon. An increase in the prevalence of DM has been observed among residents of highly arsenic-contaminated areas, whereas the findings from community-based and occupational studies in low-arsenic-exposure areas have been inconsistent. Recently, a population-based cross-sectional study showed that the current findings did not support an association between arsenic exposure from drinking water at levels less than 300 μg/L and a significantly increased risk of DM. Moreover, although the precise mechanisms for the arsenic-induced diabetogenic effect are still largely undefined, recent in vitro experimental studies indicated that inorganic arsenic or its metabolites impair insulin-dependent glucose uptake or glucose-stimulated insulin secretion. Nevertheless, the dose, the form of arsenic used, and the experimental duration in the in vivo studies varied greatly, leading to conflicting results and ambiguous interpretation of these data with respect to human exposure

  8. Early earth: Arsenic and primordial life

    NASA Astrophysics Data System (ADS)

    Kulp, Thomas R.

    2014-11-01

    Some modern microorganisms derive energy from the oxidation and reduction of arsenic. The association of arsenic with organic cellular remains in 2.7-billion-year-old stromatolites hints at arsenic-based metabolisms at the dawn of life.

  9. Comparison of radiation shielding ratios of nano-sized bismuth trioxide and molybdenum

    NASA Astrophysics Data System (ADS)

    Cho, J. H.; Kim, M. S.; Rhim, J. D.

    2015-07-01

    In this study, radiation shielding fibers using non-hazardous nano-sized bismuth trioxide and molybdenum instead of lead were developed and evaluated. Among the elements with high densities and atomic numbers, non-hazardous elements such as bismuth trioxide and molybdenum were chosen as a shielding element. Then, bismuth trioxide (Bi2O3) with average particle size 1-500 µm was ball milled for 10 min to produce a powdered form of nanoparticles with average particle size of 10-100 nm. Bismuth trioxide nanoparticles were dispersed to make a colloidal suspension, followed by spreading and hardening onto one or two sides of fabric, to create the radiation shielding fabric. The thicknesses of the shielding sheets using nano-sized bismuth and molybdenum were 0.4 and 0.7 mm. According to the lead equivalent test of X-ray shielding products suggested by KS, the equivalent dose was measured, followed by calculation of the shielding rate. The shielding rate of bismuth with 0.4 mm thickness and at 50 kVp was 90.5%, which is comparable to lead of 0.082 mm thickness. The shielding rate of molybdenum was 51.89%%, which is comparable to lead of 0.034 mm. At a thickness of 0.7 mm, the shielding rate of bismuth was 98.73%, equivalent to 0.101 mm Pb, whereas the shielding rate of molybdenum was 74.68%, equivalent to 0.045 mm Pb. In conclusion, the radiation shielding fibers using nano-sized bismuth developed in this study are capable of reducing radiation exposure by X-ray and its low-dose scatter ray.

  10. Combination of Arsenic and Interferon-α Inhibits Expression of KSHV Latent Transcripts and Synergistically Improves Survival of Mice with Primary Effusion Lymphomas

    PubMed Central

    El Hajj, Hiba; Ali, Jihane; Ghantous, Akram; Hodroj, Dana; Daher, Ahmad; Zibara, Kazem; Journo, Chloé; Otrock, Zaher; Zaatari, Ghazi; Mahieux, Renaud; El Sabban, Marwan; Bazarbachi, Ali; Abou Merhi, Raghida

    2013-01-01

    Background Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans. Methodology/Principal Findings Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN) inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice. Conclusion/Significance These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients. PMID:24250827

  11. Arsenic in shrimp from Kuwait

    SciTech Connect

    Bou-Olayan, A.H.; Al-Yakoob, S.; Al-Hossaini, M.

    1995-04-01

    Arsenic is ubiquitous in the environment and can accumulate in food via contaminated soil, water or air. It enters the food chain through dry and wet atmospheric deposition. Combustion of oil and coal, use of arsenical fertilizers and pesticides and smelting of ores contributes significantly to the natural background of arsenic in soils and sediments. The metal can be transferred from soil to man through plants. In spite of variation in acute, subacute, and chronic toxic effects to plants and animals, evidence of nutritional essentiality of arsenic for rats, goats, and guinea pigs has been suggested, but has not been confirmed for humans. Adverse toxic effects of arsenic as well as its widespread distribution in the environment raises concern about levels of arsenic in man`s diet. Higher levels of arsenic in the diet can result in a higher accumulation rate. Arsenic levels in marine organisms are influenced by species differences, size of organism, and human activities. Bottom dwellers such as shrimp, crab, and lobster accumulate more arsenic than fish due to their frequent contact with bottom sediments. Shrimp constitute approximately 30% of mean total seafood consumption in Kuwait. This study was designed to determine the accumulation of arsenic in the commercially important jinga shrimp (Metapenaeus affinis) and grooved tiger prawn (Penaeus semisulcatus). 13 refs., 3 figs., 1 tab.

  12. Arsenic Content in American Wine.

    PubMed

    Wilson, Denise

    2015-10-01

    Recent studies that have investigated arsenic content in juice, rice, milk, broth (beef and chicken), and other foods have stimulated an interest in understanding how prevalent arsenic contamination is in the U.S. food and beverage supply. The study described here focused on quantifying arsenic levels in wine. A total of 65 representative wines from the top four wine-producing states in the U.S. were analyzed for arsenic content. All samples contained arsenic levels that exceeded the U.S. Environmental Protection Agency (U.S. EPA) exposure limit for drinking water of 10 parts per billion (ppb) and all samples contained inorganic arsenic. The average arsenic detected among all samples studied was 23.3 ppb. Lead, a common co-contaminant to arsenic, was detected in 58% of samples tested, but only 5% exceeded the U.S. EPA exposure limit for drinking water of 15 ppb. Arsenic levels in American wines exceeded those found in other studies involving water, bottled water, apple juice, apple juice blend, milk, rice syrup, and other beverages. When taken in the context of consumption patterns in the U.S., the pervasive presence of arsenic in wine can pose a potential health risk to regular adult wine drinkers. PMID:26591333

  13. Synthesis and performance of bismuth trioxide nanoparticles for high energy gas generator use.

    PubMed

    Martirosyan, K S; Wang, L; Vicent, A; Luss, D

    2009-10-01

    Our experiments showed that the combustion of an Al-Bi2O3 nanoparticle mixture generated the highest pressure pulse among common nanothermite reactions and can potentially be used as a nanoenergetic gas generator. The combustion front propagation velocity and rate of energy release increased by up to three orders of magnitude when the particle size was reduced to a nanosize range for both the aluminum and the oxidizer. We developed a novel one-step (metal nitrate-glycine) combustion synthesis of nanostructured amorphous-like and highly crystalline bismuth trioxide nanoparticles. The combustion synthesis was conducted using a solution of molten bismuth nitrate as an oxidizer and glycine as a fuel. The glycine was completely combusted during the thermal decomposition of the bismuth nitrate pentahydrate and generated a temperature front that propagated through the sample. Increasing the fuel concentration increased the maximum combustion temperature from 280 to 1200 degrees C and the Bi2O3 particle size from 20 to 100 nm. The oxidizer/fuel ratio had a strong impact on the bismuth trioxide particle crystallinity. At low temperature (280 degrees C), amorphous-like bismuth trioxide nanoparticles formed, while at T > or =370 degrees C the structures were crystalline. A peak pressure of approximately 12 MPa and a thermal front propagating velocity of approximately 2500 m s(-1) were achieved during the combustion of an Al-Bi2O3 mixture containing 80 wt% of the synthesized Bi2O3 crystalline nanoparticles (size: 40-50 nm).

  14. Synthesis and performance of bismuth trioxide nanoparticles for high energy gas generator use

    NASA Astrophysics Data System (ADS)

    Martirosyan, K. S.; Wang, L.; Vicent, A.; Luss, D.

    2009-10-01

    Our experiments showed that the combustion of an Al-Bi2O3 nanoparticle mixture generated the highest pressure pulse among common nanothermite reactions and can potentially be used as a nanoenergetic gas generator. The combustion front propagation velocity and rate of energy release increased by up to three orders of magnitude when the particle size was reduced to a nanosize range for both the aluminum and the oxidizer. We developed a novel one-step (metal nitrate-glycine) combustion synthesis of nanostructured amorphous-like and highly crystalline bismuth trioxide nanoparticles. The combustion synthesis was conducted using a solution of molten bismuth nitrate as an oxidizer and glycine as a fuel. The glycine was completely combusted during the thermal decomposition of the bismuth nitrate pentahydrate and generated a temperature front that propagated through the sample. Increasing the fuel concentration increased the maximum combustion temperature from 280 to 1200 °C and the Bi2O3 particle size from 20 to 100 nm. The oxidizer/fuel ratio had a strong impact on the bismuth trioxide particle crystallinity. At low temperature (280 °C), amorphous-like bismuth trioxide nanoparticles formed, while at T>=370 °C the structures were crystalline. A peak pressure of ~12 MPa and a thermal front propagating velocity of ~2500 m s-1 were achieved during the combustion of an Al-Bi2O3 mixture containing 80 wt% of the synthesized Bi2O3 crystalline nanoparticles (size: 40-50 nm).

  15. Electrosprayed molybdenum trioxide aqueous solution and its application in organic photovoltaic cells.

    PubMed

    Suzuki, Katsumi; Fukuda, Takeshi; Liao, Yingjie

    2014-01-01

    A molybdenum trioxide thin film with smooth surface and uniform thickness was successfully achieved by an electrospray deposition method using an aqueous solution with a drastically low concentration of 0.05 wt%. Previous papers demonstrated that an additive solvent technique is useful for depositing the thin film by the electrospray deposition, and the high vapor pressure and a low surface tension of an additive solvent were found to be important factors. As a result, the smooth molybdenum trioxide thin film was obtained when the acetonitrile was used as the additive solvent. Furthermore, the vapor pressure of acetone is much higher than that of aqueous solution, and this indicates that the acetone is easily evaporated after spraying from the glass capillary. By optimizing a concentration of acetone in the molybdenum aqueous solution, a minimum root mean square roughness of the MoO3 thin film became 3.7 nm. In addition, an organic photovoltaic cell was also demonstrated using the molybdenum trioxide as a hole transport layer. Highest photoconversion efficiency was 1.72%, a value comparable to that using conventional thermal evaporation process even though the aqueous solution was used for the solution process. The photovonversion efficiency was not an optimized value, and the higher value can be achieved by optimizing the coating condition of the active layer.

  16. Efficient photoelectrochemical hydrogen production from bismuth vanadate-decorated tungsten trioxide helix nanostructures.

    PubMed

    Shi, Xinjian; Choi, Il Yong; Zhang, Kan; Kwon, Jeong; Kim, Dong Yeong; Lee, Ja Kyung; Oh, Sang Ho; Kim, Jong Kyu; Park, Jong Hyeok

    2014-01-01

    Tungsten trioxide/bismuth vanadate heterojunction is one of the best pairs for solar water splitting, but its photocurrent densities are insufficient. Here we investigate the advantages of using helical nanostructures in photoelectrochemical solar water splitting. A helical tungsten trioxide array is fabricated on a fluorine-doped tin oxide substrate, followed by subsequent coating with bismuth vanadate/catalyst. A maximum photocurrent density of ~5.35±0.15 mA cm(-2) is achieved at 1.23 V versus the reversible hydrogen electrode, and related hydrogen and oxygen evolution is also observed from this heterojunction. Theoretical simulations and analyses are performed to verify the advantages of this helical structure. The combination of effective light scattering, improved charge separation and transportation, and an enlarged contact surface area with electrolytes due to the use of the bismuth vanadate-decorated tungsten trioxide helical nanostructures leads to the highest reported photocurrent density to date at 1.23 V versus the reversible hydrogen electrode, to the best of our knowledge. PMID:25179126

  17. Electrosprayed Molybdenum Trioxide Aqueous Solution and Its Application in Organic Photovoltaic Cells

    PubMed Central

    Suzuki, Katsumi; Fukuda, Takeshi; Liao, Yingjie

    2014-01-01

    A molybdenum trioxide thin film with smooth surface and uniform thickness was successfully achieved by an electrospray deposition method using an aqueous solution with a drastically low concentration of 0.05 wt%. Previous papers demonstrated that an additive solvent technique is useful for depositing the thin film by the electrospray deposition, and the high vapor pressure and a low surface tension of an additive solvent were found to be important factors. As a result, the smooth molybdenum trioxide thin film was obtained when the acetonitrile was used as the additive solvent. Furthermore, the vapor pressure of acetone is much higher than that of aqueous solution, and this indicates that the acetone is easily evaporated after spraying from the glass capillary. By optimizing a concentration of acetone in the molybdenum aqueous solution, a minimum root mean square roughness of the MoO3 thin film became 3.7 nm. In addition, an organic photovoltaic cell was also demonstrated using the molybdenum trioxide as a hole transport layer. Highest photoconversion efficiency was 1.72%, a value comparable to that using conventional thermal evaporation process even though the aqueous solution was used for the solution process. The photovonversion efficiency was not an optimized value, and the higher value can be achieved by optimizing the coating condition of the active layer. PMID:25148047

  18. Arsenic Exposure and Toxicology: A Historical Perspective

    PubMed Central

    Hughes, Michael F.; Beck, Barbara D.; Chen, Yu; Lewis, Ari S.; Thomas, David J.

    2011-01-01

    The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve. PMID:21750349

  19. Arsenic poisoning in dairy cattle from naturally occurring arsenic pyrites.

    PubMed

    Hopkirk, R G

    1987-10-01

    An outbreak of arsenic poisoning occurred in which most of a 200 cow dairy herd were affected and six died. The source of the arsenic was naturally occurring arsenic pyrites from the Waiotapu Stream, near Rotorua. Arsenic levels in the nearby soil were as high as 6618 ppm. There was little evidence to suggest that treatment affected the course of the disease. Haematology was of little use in diagnosis, post-mortem signs were not always consistent and persistence of the element in the liver appeared short. Control of further outbreaks have been based on practical measures to minimise the intake of contaminated soil and free laying water by the stock. PMID:16031332

  20. Arsenic poisoning in dairy cattle from naturally occurring arsenic pyrites.

    PubMed

    Hopkirk, R G

    1987-10-01

    An outbreak of arsenic poisoning occurred in which most of a 200 cow dairy herd were affected and six died. The source of the arsenic was naturally occurring arsenic pyrites from the Waiotapu Stream, near Rotorua. Arsenic levels in the nearby soil were as high as 6618 ppm. There was little evidence to suggest that treatment affected the course of the disease. Haematology was of little use in diagnosis, post-mortem signs were not always consistent and persistence of the element in the liver appeared short. Control of further outbreaks have been based on practical measures to minimise the intake of contaminated soil and free laying water by the stock.

  1. Environmental aspects of arsenic toxicity.

    PubMed

    Peters, G R; McCurdy, R F; Hindmarsh, J T

    1996-01-01

    The toxicity of arsenic and its long history of use in human culture has resulted in widespread concern about the natural and anthropogenic levels of arsenic in our environment. In this article, an overview of the current environmental status of arsenic is presented. A brief history of the usage of this element is followed by a discussion of the current applications. Both natural as well as anthropogenic sources of input are described and discussed in terms of their relative impact on the Earth's environment. Numerous control mechanisms for arsenic exist in the environment, and the major processes involved (physical, chemical, and biological) are highlighted. Natural cycling of this element through the various environmental compartments (air, water, soil, and biota) are described as well as some current methods for the removal of arsenic from natural and industrial waters. Finally, a brief overview of the most common methods for the analysis of arsenic in environmental samples is presented.

  2. Prodrug strategies in anticancer chemotherapy.

    PubMed

    Kratz, Felix; Müller, Ivonne A; Ryppa, Claudia; Warnecke, André

    2008-01-01

    The majority of clinically approved anticancer drugs are characterized by a narrow therapeutic window that results mainly from a high systemic toxicity of the drugs in combination with an evident lack of tumor selectivity. Besides the development of suitable galenic formulations such as liposomes or micelles, several promising prodrug approaches have been followed in the last decades with the aim of improving chemotherapy. In this review we elucidate the two main concepts that underlie the design of most anticancer prodrugs: drug targeting and controlled release of the drug at the tumor site. Consequently, active and passive targeting using tumor-specific ligands or macromolecular carriers are discussed as well as release strategies that are based on tumor-specific characteristics such as low pH or the expression of tumor-associated enzymes. Furthermore, other strategies such as ADEPT (antibody-directed enzyme prodrug therapy) and the design of self-eliminating structures are introduced. Chemical realization of prodrug approaches is illustrated by drug candidates that have or may have clinical importance.

  3. Novel antibodies as anticancer agents.

    PubMed

    Zafir-Lavie, I; Michaeli, Y; Reiter, Y

    2007-05-28

    In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents. PMID:17530025

  4. Ganoderma: insights into anticancer effects.

    PubMed

    Kladar, Nebojša V; Gavarić, Neda S; Božin, Biljana N

    2016-09-01

    The genus Ganoderma includes about 80 species growing on cut or rotten trees. The most commonly used species is Ganoderma ludicum. Biomolecules responsible for the health benefits of Ganoderma are polysaccharides with an immunostimulative effect and triterpenes with a cytotoxic action. For more than 2000 years, it has been used traditionally in the treatment of various pathological conditions and recently, its immunoregulatory, antiviral, antibacterial, antioxidant, hepatoprotective, and anticancer potential has been confirmed. A wide range of Ganoderma extracts and preparations arrest the cell cycle in different phases and consequently inhibit the growth of various types of cancer cells. Extracts containing polysaccharides stimulate immunological reactions through the production of various cytokines and mobilization of immune system cells. In-vivo studies have confirmed the anticancer potential and the antimetastatic effects of compounds originating from Ganoderma. There is also evidence for the chemopreventive action of Ganoderma extracts in bladder, prostate, liver, and breast cancer. The results of clinical studies suggest the combined use of G. lucidum with conventional chemotherapy/radiotherapy, but the methodology and the results of these studies are being questioned. Therefore, a constant need for new clinical trials exists. PMID:26317382

  5. Moonshine-related arsenic poisoning.

    PubMed

    Gerhardt, R E; Crecelius, E A; Hudson, J B

    1980-02-01

    Twelve sequential cases of arsenic poisoning were reviewed for possible sources of ingestion. Contaminated illicit whiskey (moonshine) appeared to be the source in approximately 50% of the patients. An analysis of.confiscated moonshine revealed that occasional specimens contained high levels of arsenic as a contaminant. Although arsenic poisoning occurs relatively infrequently, contaminated moonshine may be an important cause of the poisoning in some areas of the country.

  6. Abnormal expression of 8-nitroguanine in the brain of mice exposed to arsenic subchronically.

    PubMed

    Piao, Fengyuan; Li, Sheng; Li, Qiujuan; Ye, Jianxin; Liu, Shuang

    2011-01-01

    To provide molecular toxicological evidences for exploring the mechanism of arsenic-induced neurotoxicity the accumulation of arsenic (As), the formation of 8-nitroguanine (8-NO(2)-G) were examined in brain tissue of mice exposed to arsenic. And the gene expressions of inducible NOS (iNOS), superoxide dismutase 1 (SOD1) and peroxiredoxin 2 (Prdx2) were also analyzed by GeneChip. In the result, the concentration of As in the brain tissue of mice was 4.00, 13.70, 21.48 and 29.88 ng/g in the controls and experimental groups exposed to 1, 2 and 4 mg/l As(2)O(3), respectively and increased in dose-response manner. Nervous cells in the brain of mice exposed to As showed disappearances of axons, vacuolar degeneration in cytoplasm and karyolysis, whereas no such pathological changes were observed in the control group. Weak immunoreactivity against 8-NO(2)-G was observed in the brain tissue of mice given 1 or 2 ppm arsenic trioxide. More intensive immunoreactivity was found in cells at 4 ppm and it was mainly distributed in cytoplasm. The expressions of SOD1 and Prdx2 were down-regulated in the brain of mice exposed to As, but iNOS expression was not disturbed by As exposure. No the 8-NO(2)-G immunoreactivity or abnormal expressions of these genes in brain tissue were observed in controls. These results indicate that As induces high expression of 8-NO(2)-G in brain tissues of mice and that RNA in the cells may be modified by overproduced reactive nitrogen species.

  7. Arsenic poisoning of Bangladesh groundwater

    NASA Astrophysics Data System (ADS)

    Nickson, Ross; McArthur, John; Burgess, William; Ahmed, Kazi Matin; Ravenscroft, Peter; Rahmanñ, Mizanur

    1998-09-01

    In Bangladesh and West Bengal, alluvial Ganges aquifers used for public water supply are polluted with naturally occurring arsenic, which adversely affects the health of millions of people. Here we show that the arsenic derives from the reductive dissolution of arsenic-rich iron oxyhydroxides, which in turn are derived from weathering of base-metal sulphides. This finding means it should now be possible, by sedimentological study of the Ganges alluvial sediments, to guide the placement of new water wells so they will be free of arsenic.

  8. Arsenic content of homeopathic medicines

    SciTech Connect

    Kerr, H.D.; Saryan, L.A.

    1986-01-01

    In order to test the widely held assumption that homeopathic medicines contain negligible quantities of their major ingredients, six such medicines labeled in Latin as containing arsenic were purchased over the counter and by mail order and their arsenic contents measured. Values determined were similar to those expected from label information in only two of six and were markedly at variance in the remaining four. Arsenic was present in notable quantities in two preparations. Most sales personnel interviewed could not identify arsenic as being an ingredient in these preparations and were therefore incapable of warning the general public of possible dangers from ingestion. No such warnings appeared on the labels.

  9. Can folate intake reduce arsenic toxicity?

    PubMed

    Kile, Molly L; Ronnenberg, Alayne G

    2008-06-01

    Arsenic-contaminated groundwater is a global environmental health concern. Inorganic arsenic is a known carcinogen, and epidemiologic studies suggest that persons with impaired arsenic metabolism are at increased risk for certain cancers, including skin and bladder carcinoma. Arsenic metabolism involves methylation to monomethylarsonic acid and dimethylarsinic acid (DMA) by a folate-dependent process. Persons possessing polymorphisms in certain genes involved in folate metabolism excrete a lower proportion of urinary arsenic as DMA, which may influence susceptibility to arsenic toxicity. A double-blind placebo-controlled trial in a population with low plasma folate observed that after 12 weeks of folic acid supplementation, the proportion of total urinary arsenic excreted as DMA increased and blood arsenic concentration decreased, suggesting an improvement in arsenic metabolism. Although no studies have directly shown that high folate intake reduces the risk of arsenic toxicity, these findings provide evidence to support an interaction between folate and arsenic metabolism.

  10. Electronic structure of trioxide, oxoperoxide, oxosuperoxide, and ozonide clusters of the 3d elements: density functional theory study.

    PubMed

    Uzunova, Ellie L

    2011-03-01

    The trioxide clusters with stoichiometry MO3, and the structural isomers with side-on and end-on bonded oxygen atoms, are studied by DFT with the B1LYP functional. For the first half of the 3d elements row (Sc to Cr), pyramidal or distorted pyramidal structures dominate among the trioxide and oxoperoxide ground states, while the remaining elements form planar trioxides, oxoperoxides, oxosuperoxides, and ozonides. Low-lying trioxide clusters are formed by Ti, V, Cr, and Mn, among which the distorted pyramidal VO3 in the (2)A'' state, the pyramidal CrO3 in the (1)A1 state, and the planar MnO3 in the (2)A1' state are global minima. With the exception of the middle-row elements Mn, Fe, and Co, the magnetic moment of the ground-state clusters is formed with a major contribution from unpaired electrons located at the oxygen atoms. The stability of trioxides and oxoperoxides toward release of molecular oxygen is significantly higher for Sc, Ti, and V than for the remaining elements of the row. A trend of increasing the capability to dissociate one oxygen molecule is observed from Cr to Cu, with the exception of OFe(O2) being more reactive than OCo(O2). A gradual increase of reactivity from Ti to Cu is observed for the complete fragmentation reaction M + O + O2.

  11. Anticancer agents derived from natural cinnamic acids.

    PubMed

    Su, Ping; Shi, Yaling; Wang, Jinfeng; Shen, Xiuxiu; Zhang, Jie

    2015-01-01

    Cancer is the most dangerous disease that causes deaths all over the world. Natural products have afforded a rich source of drugs in a number of therapeutic fields including anticancer agents. Many significant drugs have been derived from natural sources by structural optimization of natural products. Cinnamic acid has gained great interest due to its antiproliferative, antioxidant, antiangiogenic and antitumorigenic potency. Currently it has been observed that cinnamic acid and its analogs such as caffeic acid, sinapic acid, ferulic acid, and isoferulic acid display various pharmacological activities, such as immunomodulation, anti-inflammation, anticancer and antioxidant. They have served to be the major sources of potential leading anticancer compounds. In this review, we focus on the anticancer potency of cinnamic acid derivatives and novel strategies to design these derivatives. We hope this review will be useful for researchers who are interested in developing anticancer agents.

  12. [Subacute arsenic poisoning].

    PubMed

    Ghariani, M; Adrien, M L; Raucoules, M; Bayle, J; Jacomet, Y; Grimaud, D

    1991-01-01

    A cas is reported of a 23-year-old man who voluntarily took a massive dose of arsenic (at least 8 g). In spite of the ingested amount and the acute nature of the poisoning, the patient survived 8 days. Gastrointestinal, neurologic and cardiac features were predominant including nausea, vomiting, choleroid diarrhoea, encephalopathy, peripheral neuropathy, and finally a fatal toxic cardiomyopathy. Metabolic acidosis, moderate cytolysis and an anticoagulant effect were also observed. This unique characteristic was partly due to a circulating anticoagulant with prothrombinase activity, as well as direct antivitamin K activity. Postmortem examination revealed: a congestive oesophagitis; a necrosing gastritis involving all the stomach wall; diffuse hepatic steatosis; skin lesions with vascular congestion and dermoepidermal detachment; discrete subepicardial congestive lesions. Arsenic was found in all tissues.

  13. Bovine arsenic toxicosis.

    PubMed

    Neiger, Regg; Nelson, Nicole; Miskimins, Dale; Caster, Jim; Caster, Larry

    2004-09-01

    A ranch in central South Dakota had a number of dead calves because of arsenic poisoning. The clinical picture included diarrhea, central nervous system signs, and death. Gross necropsy findings included adequate body fat, stomachs full of normal-appearing ingesta, and large amounts of greenish brown watery fluid in the intestine and colon. Microscopically there was severe lymphoid tissue necrosis in the mesenteric lymph nodes and gut-associated lymphoid tissue. Chemical analysis of kidneys showed no significant amounts of lead; however, kidney arsenic concentrations were 25 to 44 ppm. The source was a small pile of Paris Green (common name for cupric acetoarsenite) found in an old dump site in the pasture.

  14. 40 CFR 61.186 - Reporting requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... alternative arsenic trioxide production processes. Conclusions and recommendations of the studies shall...

  15. 40 CFR 61.186 - Reporting requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... alternative arsenic trioxide production processes. Conclusions and recommendations of the studies shall...

  16. 40 CFR 61.186 - Reporting requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... alternative arsenic trioxide production processes. Conclusions and recommendations of the studies shall...

  17. 40 CFR 61.186 - Reporting requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... alternative arsenic trioxide production processes. Conclusions and recommendations of the studies shall...

  18. 40 CFR 61.186 - Reporting requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... alternative arsenic trioxide production processes. Conclusions and recommendations of the studies shall...

  19. 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...

  20. Homicidal arsenic poisoning.

    PubMed

    Duncan, Andrew; Taylor, Andrew; Leese, Elizabeth; Allen, Sam; Morton, Jackie; McAdam, Julie

    2015-07-01

    The case of a 50-year-old man who died mysteriously after being admitted to hospital is reported. He had raised the possibility of being poisoned prior to his death. A Coroner's post-mortem did not reveal the cause of death but this was subsequently established by post-mortem trace element analysis of liver, urine, blood and hair all of which revealed very high arsenic concentrations.

  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. Arsenic speciation in edible mushrooms.

    PubMed

    Nearing, Michelle M; Koch, Iris; Reimer, Kenneth J

    2014-12-16

    The fruiting bodies, or mushrooms, of terrestrial fungi have been found to contain a high proportion of the nontoxic arsenic compound arsenobetaine (AB), but data gaps include a limited phylogenetic diversity of the fungi for which arsenic speciation is available, a focus on mushrooms with higher total arsenic concentrations, and the unknown formation and role of AB in mushrooms. To address these, the mushrooms of 46 different fungus species (73 samples) over a diverse range of phylogenetic groups were collected from Canadian grocery stores and background and arsenic-contaminated areas. Total arsenic was determined using ICP-MS, and arsenic speciation was determined using HPLC-ICP-MS and complementary X-ray absorption spectroscopy (XAS). The major arsenic compounds in mushrooms were found to be similar among phylogenetic groups, and AB was found to be the major compound in the Lycoperdaceae and Agaricaceae families but generally absent in log-growing mushrooms, suggesting the microbial community may influence arsenic speciation in mushrooms. The high proportion of AB in mushrooms with puffball or gilled morphologies may suggest that AB acts as an osmolyte in certain mushrooms to help maintain fruiting body structure. The presence of an As(III)-sulfur compound, for the first time in mushrooms, was identified in the XAS analysis. Except for Agaricus sp. (with predominantly AB), inorganic arsenic predominated in most of the store-bought mushrooms (albeit with low total arsenic concentrations). Should inorganic arsenic predominate in these mushrooms from contaminated areas, the risk to consumers under these circumstances should be considered.

  3. Bacteriocins as Potential Anticancer Agents

    PubMed Central

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies. PMID:26617524

  4. Bacteriocins as Potential Anticancer Agents.

    PubMed

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies.

  5. [Anticancer propaganda: myth or reality?].

    PubMed

    Demin, E V; Merabishvili, V M

    2014-01-01

    The authors raise a very important problem of anticancer propaganda aimed at the early detection of cancer to be solved nowadays by means of screening and constructive interaction between oncologists and the public. To increase the level of knowledge of the population in this area it is necessary to expand the range of its adequate awareness of tumor diseases. Only joint efforts can limit the destructive effect of cancer on people's minds, so that every person would be responsible for his own health, clearly understanding the advantages of early visit to a doctor. This once again highlights the need of educational work with the public, motivational nature of which allows strengthening the value of screening in the whole complex of measures to fight cancer.

  6. Unusual manifestations of arsenic intoxication.

    PubMed

    Zaloga, G P; Deal, J; Spurling, T; Richter, J; Chernow, B

    1985-05-01

    A patient with arsenic intoxication is reported, who presented with a variety of gastrointestinal and neurologic disturbances including unilateral facial nerve palsy and acute symptomatic pancreatitis, neither of which have been previously described as sequelae of arsenic poisoning. The patient also suffered hematologic, dermatologic, and cardiopulmonary complications. A review of the literature about this interesting problem is also presented.

  7. Acute arsenical poisoning in Dunedin.

    PubMed

    Gillies, A J; Taylor, A J

    1979-05-23

    Four cases of acute poisoning with arsenic are described. Although no new approach to therapy is proposed it is suggested from the data of arsenic recovery from the dialysate of one of the patients studied, that peritoneal dialysis is unlikely to be satisfactory.

  8. Arsenic Is A Genotoxic Carcinogen

    EPA Science Inventory

    Arsenic is a recognized human carcinogen; however, there is controversy over whether or not it should be considered a genotoxic carcinogen. Many possible modes of action have been proposed on how arsenic induces cancer, including inhibiting DNA repair, altering methylation patter...

  9. Arsenic Removal from Drinking Water

    EPA Science Inventory

    Web cast presentation covered six topics: 1), Arsenic Chemistry, 2), Technology Selection/Arsenic Demonstration Program, 3), Case Study 1, 4), Case Study 2,5), Case Study 3, and 6), Media Regeneration Project. The presentation consists of material presented at other training sess...

  10. TREATMENT TECHNOLOGIES FOR ARSENIC REMOVAL

    EPA Science Inventory

    The United States Environmental Protection Agency (US EPA) recently reduced the arsenic maximum contaminant level (MCL) from 0.050 mg/L to 0.010 mg/L. In order to increase arsenic outreach efforts, a summary of the new rule, related health risks, treatment technologies, and desig...

  11. ARSENIC - SUSCEPTIBILITY & IN UTERO EFFECTS

    EPA Science Inventory

    Exposure to inorganic arsenic remains a serious public health problem at many locations worldwide. If has often been noted that prevalences of signs and symptoms of chronic arsenic poisoning differ among various populations. For example, skin lesions or peripheral vascular dis...

  12. Testicular toxicity evaluation of arsenic-containing binary compound semiconductors, gallium arsenide and indium arsenide, in hamsters.

    PubMed

    Omura, M; Hirata, M; Tanaka, A; Zhao, M; Makita, Y; Inoue, N; Gotoh, K; Ishinishi, N

    1996-12-16

    The testicular toxicities of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were examined by repetitive intratracheal instillation using hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) were instilled twice a week a total of 16 times and InAs (7.7 mg/kg) was instilled a total of 14 times. GaAs caused testicular spermatid retention and epididymal sperm reduction, though the degrees were less severe than those in rats shown in our previous experiment. InAs and As2O3 did not show any testicular toxicities. Serum arsenic concentration in GaAs-treated hamsters was less than half of that in As2O3-treated hamsters in which no testicular toxicities were found. Serum molar concentration of gallium was 32-times higher than that of arsenic in GaAs-treated hamsters. Therefore gallium may play a main role in the testicular toxicity of GaAs in hamsters.

  13. Arsenic Mobility and Groundwater Extraction in Bangladesh

    NASA Astrophysics Data System (ADS)

    Harvey, Charles F.; Swartz, Christopher H.; Badruzzaman, A. B. M.; Keon-Blute, Nicole; Yu, Winston; Ali, M. Ashraf; Jay, Jenny; Beckie, Roger; Niedan, Volker; Brabander, Daniel; Oates, Peter M.; Ashfaque, Khandaker N.; Islam, Shafiqul; Hemond, Harold F.; Ahmed, M. Feroze

    2002-11-01

    High levels of arsenic in well water are causing widespread poisoning in Bangladesh. In a typical aquifer in southern Bangladesh, chemical data imply that arsenic mobilization is associated with recent inflow of carbon. High concentrations of radiocarbon-young methane indicate that young carbon has driven recent biogeochemical processes, and irrigation pumping is sufficient to have drawn water to the depth where dissolved arsenic is at a maximum. The results of field injection of molasses, nitrate, and low-arsenic water show that organic carbon or its degradation products may quickly mobilize arsenic, oxidants may lower arsenic concentrations, and sorption of arsenic is limited by saturation of aquifer materials.

  14. In situ chemical fixation of arsenic-contaminated soils: Anexperimental study

    SciTech Connect

    Yang, Li; Donahoe, Rona J.; Redwine, James C.

    2007-03-27

    This paper reports the results of an experimentalstudytesting a low-cost in situ chemical fixation method designed to reclaimarsenic-contaminated subsurface soils. Subsurface soils from severalindustrial sites in southeastern U.S. were contaminated with arsenicthrough heavy application of herbicide containing arsenic trioxide. Themean concentrations of environmentally available arsenic in soilscollected from the two study sites, FW and BH, are 325 mg/kg and 900mg/kg, respectively. The soils are sandy loams with varying mineralogicaland organic contents. The previous study [Yang L, Donahoe RJ. The form,distribution and mobility of arsenic in soils contaminated by arsenictrioxide, at sites in Southeast USA. Appl Geochem 2007;22:320 341]indicated that a large portion of the arsenic in both soils is associatedwith amorphous aluminum and iron oxyhydroxides and shows very slowrelease against leaching by synthetic precipitation. The soil's amorphousaluminum and iron oxyhydroxides content was found to have the mostsignificant effect on its ability to retain arsenic.Based on thisobservation, contaminated soils were reacted with different treatmentsolutions in an effort to promote the formation of insolublearsenic-bearing phases and thereby decrease the leachability of arsenic.Ferrous sulfate, potassium permanganate and calcium carbonate were usedas the reagents for the chemical fixation solutions evaluated in threesets of batch experiments: (1) FeSO4; (2) FeSO4 and KMnO4; (3) FeSO4,KMnO4 and CaCO3. The optimum treatment solutions for each soil wereidentified based on the mobility of arsenic during sequential leaching oftreated and untreated soils using the fluids described in EPA Method 1311[USEPA. Method 1311: toxicity characteristic leaching procedure. Testmethods for evaluating solid waste, physical/chemical methods. 3rd ed.Washington, DC: U.S. Environmental Protection Agency, Office of SolidWaste. U.S. Government Printing Office; 1992]toxic characteristicsleaching

  15. Total arsenic in rice milk.

    PubMed

    Shannon, Ron; Rodriguez, Jose M

    2014-01-01

    Rice milk and its by-products were tested for total arsenic concentration. Total arsenic concentration was determined using graphite-furnace atomic absorption spectrometry. The arsenic concentrations ranged from 2.7 ± 0.3 to 17.9 ± 0.5 µg L(-1). Rice milk and its by-products are not clearly defined as food, water or milk substitute. The US Environmental Protection Agency (EPA), the European Union (EU) and the World Health Organization (WHO) have set a level of 10 µg L(-1) for total arsenic concentrations in drinking water. The EU and the US regulatory agencies do not provide any guidelines on total arsenic concentrations in foods. This study provides us with a starting point to address this issue in the State of Mississippi, USA.

  16. Uncertainties drive arsenic rule delay

    SciTech Connect

    Pontius, F.W.

    1995-04-01

    The US Environmental Protection Agency (USEPA) is under court order to sign a proposed rule for arsenic by Nov. 30, 1995. The agency recently announced that it will not meet this deadline, citing the need to gather additional information. Development of a National Interim Primary Drinking Water Regulation for arsenic has been delayed several times over the past 10 years because of uncertainties regarding health issues and costs associated with compliance. The early history of development of the arsenic rule has been reviewed. Only recent developments are reviewed here. The current maximum contaminant level (MCL) for arsenic in drinking water is 0.05 mg/L. This MCL was set in 1975, based on the 1962 US Public Health Standards. The current Safe Drinking Water Act (SDWA) requires that the revised arsenic MCL be set as close to the MCL goal (MCLG) as is feasible using best technology, treatment techniques, or other means and taking cost into consideration.

  17. [Investigation of chronic arsenic poisoning caused by high arsenic coal pollution].

    PubMed

    Zhou, D X

    1993-05-01

    This article reports the results of an investigation on environmental arsenic pollution and chronic arsenic poisoning in a rural area. Exploitation of high arsenic coal caused drinking and irrigating water to be polluted by arsenic and burning of this coal caused severe environmental arsenic pollution including air, food, soil and drinking well water. 1548 villagers in 47 villages suffered from chronic arsenic poisoning who used this coal in daily life. The polluted air and food were mainly responsible, while the polluted drinking water and skin absorption played some part in poisoning. When arsenic level in coal is as high as 100mg/kg, we should consider the possibility of environmental arsenic pollution and chronic arsenic poisoning in exposed population. The high arsenic coal's distribution is very uneven. When controlling the disease, it is important to remember monitoring the quantity of arsenic coal outside the arsenic coal mining area. PMID:8243176

  18. THE ROLE OF PROTEIN BINDING OF TRIVALENT ARSENICALS IN ARSENIC CARCINOGENESIS AND TOXICITY

    EPA Science Inventory

    Three of the most plausible biological theories of arsenic carcinogenesis are protein binding, oxidative stress and altered DNA methylation. This review presents the role of trivalent arsenicals binding to proteins in arsenic carcinogenesis. Using vacuum filtration based receptor...

  19. *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. A comparative genomic approach focused on Ciona intestinaJis, an invertebrate chordate, was u...

  20. Plant antimicrobial peptides as potential anticancer agents.

    PubMed

    Guzmán-Rodríguez, Jaquelina Julia; Ochoa-Zarzosa, Alejandra; López-Gómez, Rodolfo; López-Meza, Joel E

    2015-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy.

  1. Anticancer Advances of Matrine and Its Derivatives.

    PubMed

    Yong, Jianping; Wu, Xiaoyuan; Lu, Canzhong

    2015-01-01

    As the second leading cause of death in the world, the total number caused by cancer in 2008 is 1.4 million. The great cancer incidence worldwide increases the search for new, safer and efficient anticancer agents (especially to find the new structures and more active anticancer drugs from the natural products) aiming the prevention or the cure of such illness. For a century, matrine (an alkaloid isolated from sophorae flavescens Ait.) has been widely studied in the field of cancer. This review briefly describes the progress of matrine, its derivatives and their anticancer activity.

  2. Plant Antimicrobial Peptides as Potential Anticancer Agents

    PubMed Central

    Guzmán-Rodríguez, Jaquelina Julia; López-Gómez, Rodolfo

    2015-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy. PMID:25815333

  3. Self-assembled flower-like antimony trioxide microstructures with high infrared reflectance performance

    SciTech Connect

    Ge, Shengsong; Yang, Xiaokun; Shao, Qian; Liu, Qingyun; Wang, Tiejun; Wang, Lingyun; Wang, Xiaojie

    2013-04-15

    A simple hydrothermal process was adopted to self-assembly prepare high infrared reflective antimony trioxide with three-dimensional flower-like microstructures. The morphologies of antimony trioxide microstructures were characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and high resolution transmission electron microscopy (HRTEM) respectively. It is also found that experimental parameters, such as NaOH concentration, surfactant concentration and volume ratio of ethanol–water played crucial roles in controlling the morphologies of Sb{sub 2}O{sub 3} microstructures. A possible growth mechanism of flower-like Sb{sub 2}O{sub 3} microstructure was proposed based on the experimental data. UV–vis–NIR spectra verified that the near infrared reflectivity of the obtained flower-like microstructures could averagely achieve as 92% with maximum reflectivity of 98%, obviously higher than that of other different morphologies of antimony trioxide microstructures. It is expected that the flower-like Sb{sub 2}O{sub 3} nanostructures have some applications in optical materials and heat insulation coatings. - Graphical abstract: Flower-like Sb{sub 2}O{sub 3} microstructures that composed of nanosheets with thickness of ca. 100 nm exhibit high reflectivity under UV–vis–NIR spectra. Highlights: ► Uniform flower-like microstructures were synthesized via simple hydrothermal reaction. ► The flower-like Sb{sub 2}O{sub 3} microstructures exhibited higher reflectivity than other morphologies under the UV–vis–NIR light. ► Influencing parameters on the Sb{sub 2}O{sub 3} morphologies have been discussed in detail. ► Possible mechanism leading to flower-like microstructures was proposed.

  4. Polymerization of aniline in the interlayer space of molybdenum trioxide and its electrochemical properties

    SciTech Connect

    Li Yanping; Xiang Yixian; Dong Xiaowen; Xu Jiaqiang; Ruan Fei; Pan Qingyi

    2009-08-15

    Molybdenum trioxide/polyaniline (MoO{sub 3}/PANI) composite was prepared first by ion-exchange reaction between aniline (ANI) and dodecylamine (DDA) which was intercalated precursor, and then was formed under the polymerization of ANI within the interlayer space of MoO{sub 3} at 120 deg. C for 3 d in air. According to powder X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, infrared spectroscopy and electrochemical testing, MoO{sub 3}/PANI composite has layered structure, and its interlayer spacing is 1.127 nm. Moreover, it has high thermal stability with the compound and completes its weight loss at 751.9 deg. C. Electrochemical investigation shows that MoO{sub 3} is the major active substance in the MoO{sub 3}/PANI electrode, and MoO{sub 3}/PANI electrode demonstrates better conductivity and electrochemical activity than pure MoO{sub 3} electrode, attributed to the promotion of Li{sup +} and/or electron transport. In addition, the alternating current impedance proves that if the resistance of MoO{sub 3}/PANI electrode reduces apparently, the electrochemical activity will increase correspondingly, the same as the relationship between the ohmic resistance and the electrical conductivity. - Graphical abstract: Aniline (ANI) monomer was intercalated into the interlayer space of molybdenum trioxide (MoO{sub 3}) and heat-treated at 120 deg. C for 3 d in air, and then polymerized to form layered structure of molybdenum trioxide/polyaniline (MoO{sub 3}/PANI) composite. Its interlayer spacing of MoO{sub 3}/PANI composite is 1.127 nm.

  5. Arsenic concentrations in Chinese coals.

    PubMed

    Wang, Mingshi; Zheng, Baoshan; Wang, Binbin; Li, Shehong; Wu, Daishe; Hu, Jun

    2006-03-15

    The arsenic concentrations in 297 coal samples were collected from the main coal-mines of 26 provinces in China were determined by molybdenum blue coloration method. These samples were collected from coals that vary widely in coal rank and coal-forming periods from the five main coal-bearing regions in China. Arsenic content in Chinese coals range between 0.24 to 71 mg/kg. The mean of the concentration of Arsenic is 6.4+/-0.5 mg/kg and the geometric mean is 4.0+/-8.5 mg/kg. The level of arsenic in China is higher in northeastern and southern provinces, but lower in northwestern provinces. The relationship between arsenic content and coal-forming period, coal rank is studied. It was observed that the arsenic contents decreases with coal rank in the order: Tertiary>Early Jurassic>Late Triassic>Late Jurassic>Middle Jurassic>Late Permian>Early Carboniferous>Middle Carboniferous>Late Carboniferous>Early Permian; It was also noted that the arsenic contents decrease in the order: Subbituminous>Anthracite>Bituminous. However, compared with the geological characteristics of coal forming region, coal rank and coal-forming period have little effect on the concentration of arsenic in Chinese coal. The average arsenic concentration of Chinese coal is lower than that of the whole world. The health problems in China derived from in coal (arsenism) are due largely to poor local life-style practices in cooking and home heating with coal rather than to high arsenic contents in the coal.

  6. Arsenic concentrations in Chinese coals.

    PubMed

    Wang, Mingshi; Zheng, Baoshan; Wang, Binbin; Li, Shehong; Wu, Daishe; Hu, Jun

    2006-03-15

    The arsenic concentrations in 297 coal samples were collected from the main coal-mines of 26 provinces in China were determined by molybdenum blue coloration method. These samples were collected from coals that vary widely in coal rank and coal-forming periods from the five main coal-bearing regions in China. Arsenic content in Chinese coals range between 0.24 to 71 mg/kg. The mean of the concentration of Arsenic is 6.4+/-0.5 mg/kg and the geometric mean is 4.0+/-8.5 mg/kg. The level of arsenic in China is higher in northeastern and southern provinces, but lower in northwestern provinces. The relationship between arsenic content and coal-forming period, coal rank is studied. It was observed that the arsenic contents decreases with coal rank in the order: Tertiary>Early Jurassic>Late Triassic>Late Jurassic>Middle Jurassic>Late Permian>Early Carboniferous>Middle Carboniferous>Late Carboniferous>Early Permian; It was also noted that the arsenic contents decrease in the order: Subbituminous>Anthracite>Bituminous. However, compared with the geological characteristics of coal forming region, coal rank and coal-forming period have little effect on the concentration of arsenic in Chinese coal. The average arsenic concentration of Chinese coal is lower than that of the whole world. The health problems in China derived from in coal (arsenism) are due largely to poor local life-style practices in cooking and home heating with coal rather than to high arsenic contents in the coal. PMID:16256172

  7. Polymeric micelles for GSH-triggered delivery of arsenic species to cancer cells.

    PubMed

    Zhang, Qi; Vakili, Mohammad Reza; Li, Xing-Fang; Lavasanifar, Afsaneh; Le, X Chris

    2014-08-01

    Arsenic trioxide (ATO), dissolved in water as arsenous acid or inorganic arsenite (As(III)), is an effective chemotherapeutic agent against acute promyelocytic leukemia (APL). It has been under investigation as a potential treatment for a variety of solid tumors although with much poorer efficacy than for APL. The toxicity of As(III) and its derivatives is a common concern that has limited its use. The objective of the current study was to develop a polymeric micelle drug delivery system for efficient and controlled delivery of trivalent arsenicals to solid tumor cells. A polymeric micelle-based drug delivery system can potentially extend the duration of drug circulation in blood, restrict access of encapsulated drug to normal tissues, achieve tumor targeted drug delivery, enhance drug accumulation in the tumor area, and trigger drug release at tumor sites if designed properly. These, in turn, can lead to an improved therapeutic index for the polymeric micellar formulation of arsenic species compared to their free form. Towards this goal, a biodegradable block copolymer with pendent thiol groups on the hydrophobic block, i.e., methoxy poly(ethylene oxide)-block-poly[α-(6-mecaptohexyl amino)carboxylate-ε-caprolactone] [PEO-b-P(CCLC6-SH)], was synthesized and used for conjugation of a trivalent arsenical, phenylarsine oxide (PAO), to free thiol groups on the polymer backbone. PAO-loaded micelles had refined size distribution with an average diameter of 150 nm as evidenced by dynamic light scattering (DLS) in water. Prepared polymeric micelles were characterized for the level of PAO conjugation using inductively coupled plasma mass spectrometry (ICP-MS). The results showed 65% of total free thiols were conjugated to PAO providing an arsenic/polymer loading content of ~2.5 wt%. In vitro release study suggests prolonged release of PAO from its polymeric micellar carrier, which was accelerated in the presence of glutathione (GSH). Cytotoxicity studies against MDA

  8. Levels of arsenic in Indian opium eaters.

    PubMed

    Narang, A P; Chawla, L S; Khurana, S B

    1987-11-01

    Intake of opium is very common in India. The contraband material is generally contaminated with arsenic. Most often opium eaters present with neuropathy and hepatomegaly. Arsenic was estimated in serum, urine, nails and hair of opium eaters with and without neuropathy. Arsenic was also estimated in various opium samples. Arsenic was significantly higher in serum, urine, nails and hair of opium addicts when compared to controls. The opium samples analysed showed varyingly high amounts of arsenic.

  9. Production of selenium-72 and arsenic-72

    DOEpatents

    Phillips, Dennis R.

    1994-01-01

    Methods and apparatus for producing selenium-72, separating it from its daughter isotope arsenic-72, and generating multiple portions of a solution containing arsenic-72 from a reusable parent substance comprised of selenium-72. The invention provides apparatus which can be located at a site where arsenic-72 is used, for purposes such as PET imaging, to produce arsenic-72 as needed, since the half-life of arsenic-72 is very short.

  10. Production of selenium-72 and arsenic-72

    DOEpatents

    Phillips, D.R.

    1994-12-06

    Methods and apparatus are described for producing selenium-72, separating it from its daughter isotope arsenic-72, and generating multiple portions of a solution containing arsenic-72 from a reusable parent substance comprised of selenium-72. The invention provides apparatus which can be located at a site where arsenic-72 is used, for purposes such as PET imaging, to produce arsenic-72 as needed, since the half-life of arsenic-72 is very short. 2 figures.

  11. Production of selenium-72 and arsenic-72

    DOEpatents

    Phillips, Dennis R.

    1995-01-01

    Methods and apparatus for producing selenium-72, separating it from its daughter isotope arsenic-72, and generating multiple portions of a solution containing arsenic-72 from a reusable parent substance comprised of selenium-72. The invention provides apparatus which can be located at a site where arsenic-72 is used, for purposes such as PET imaging, to produce arsenic-72 as needed, since the half-life of arsenic-72 is very short.

  12. 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

  13. Photoelectrochemical and physical properties of tungsten trioxide films obtained by aerosol pyrolysis

    SciTech Connect

    Sadale, S.B.; Chaqour, S.M.; Gorochov, O.; Neumann-Spallart, M.

    2008-06-03

    Aerosol pyrolysis (AP) was used for preparing semiconducting films of tungsten trioxide using peroxotungstic acid as a precursor. The films were characterized by SEM, XRD, and by their photoelectrochemical response. Porous, polycrystalline (monoclinic) films of thickness up to 3 {mu}m were prepared. An incident photon to current efficiency (IPCE) of 0.55 at 365 nm was obtained for films of 1 {mu}m thickness on conducting F:SnO{sub 2}/glass substrates under depletion conditions, in junctions with aqueous electrolytes. The spectral (photocurrent) response extended into the visible region (up to 470 nm) which is of importance for solar applications like photocatalysis.

  14. Obturating teeth with wide open apices using mineral trioxide aggregate: a case report.

    PubMed

    Levenstein, H

    2002-07-01

    The conventional approach in handling a tooth with a wide open apex requiring endodontic treatment is by means of a procedure called apexification. The objective of treatment is to introduce calcium hydroxide mixed with sterile water or local anaesthetic into the root canal to create a hard-tissue-like formation or an apical plug to prevent extrusion of filling materials during obturation of teeth with wide open apices. This procedure may take anything from 6 months to 2 years. In 1999 a new material called mineral trioxide aggregate (MTA) was introduced to the dental profession for clinical use which has the ability to create an apical plug within a few weeks.

  15. Photoelectrochemical water splitting at titanium dioxide nanotubes coated with tungsten trioxide

    SciTech Connect

    Park, Jong Hyeok; Park, O Ok; Kim, Sungwook

    2006-10-16

    The photocatalytic splitting of water into hydrogen and oxygen using solar light is a potentially clean and renewable source for hydrogen fuel. Titanium oxide nanotubes coated with tungsten oxide were prepared to harvest more solar light for the first time and characterized their water splitting efficiency. The tungsten trioxide coatings significantly enhanced the visible spectrum absorption of the titanium dioxide nanotube array, as well as their solar-spectrum induced photocurrents. For the sample, upon white light illumination at 150 mW/cm{sup 2}, hydrogen gas generated at the overall conversion efficiency of 0.87%.

  16. Furcal-perforation repair with mineral trioxide aggregate: Two years follow-up.

    PubMed

    da Silva, Emmanuel João Nogueira Leal; Andrade, Carlos Vieira; Tay, Lidia Yileng; Herrera, Daniel Rodrigo

    2012-01-01

    Furcal perforations are significant iatrogenic complications of endodontic treatment and could lead to endodontic failure. Mineral trioxide aggregate (MTA) has been regarded as an ideal material for perforation repair, retrograde filling, pulp capping, and apexification. This case report describes a furcal perforation in a maxillary first molar, which was repaired using MTA. The tooth was endodontically treated and coronally restored with resin composite. After 2 years, the absence of periradicular radiolucent lesions, pain, and swelling along with functional tooth stability indicated a successful outcome of sealing the perforation using MTA. PMID:23257493

  17. White mineral trioxide aggregate pulpotomies: Two case reports with long-term follow-up.

    PubMed

    Emine, Sen Tunc; Tuba, Ulusoy Ayca

    2011-10-01

    This case report describes the partial pulpotomy treatment of complicated crown fractures of two cases by using white mineral trioxide aggregate (WMTA) with long-term follow-up. In the cases presented here, to injured incisor teeth were open apices and the pulp exposure site was large, so it was decided to perform vital pulpotomy with WMTA. Long-term follow-up examinations revealed that the treatment preserved pulpal vitality with continued root development and apex formation. WMTA may be considered as an alternative option for the treatment of traumatized immature permanent teeth.

  18. Arsenic Mediated Disruption of Promyelocytic Leukemia Protein Nuclear Bodies Induces Ganciclovir Susceptibility in Epstein-Barr Positive Epithelial Cells

    PubMed Central

    Sides, Mark D.; Block, Gregory J.; Shan, Bin; Esteves, Kyle C.; Lin, Zhen; Flemington, Erik K.; Lasky, Joseph A.

    2011-01-01

    Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies. PMID:21605886

  19. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells.

    PubMed

    Sides, Mark D; Block, Gregory J; Shan, Bin; Esteves, Kyle C; Lin, Zhen; Flemington, Erik K; Lasky, Joseph A

    2011-07-20

    Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies. PMID:21605886

  20. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells

    SciTech Connect

    Sides, Mark D.; Block, Gregory J.; Shan, Bin; Esteves, Kyle C.; Lin, Zhen; Flemington, Erik K.; Lasky, Joseph A.

    2011-06-20

    Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.

  1. Anticancer Properties of Capsaicin Against Human Cancer.

    PubMed

    Clark, Ruth; Lee, Seong-Ho

    2016-03-01

    There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities. PMID:26976969

  2. Development of synthetic lethality anticancer therapeutics.

    PubMed

    Fang, Bingliang

    2014-10-01

    The concept of synthetic lethality (the creation of a lethal phenotype from the combined effects of mutations in two or more genes) has recently been exploited in various efforts to develop new genotype-selective anticancer therapeutics. These efforts include screening for novel anticancer agents, identifying novel therapeutic targets, characterizing mechanisms of resistance to targeted therapy, and improving efficacies through the rational design of combination therapy. This review discusses recent developments in synthetic lethality anticancer therapeutics, including poly ADP-ribose polymerase inhibitors for BRCA1- and BRCA2-mutant cancers, checkpoint inhibitors for p53 mutant cancers, and small molecule agents targeting RAS gene mutant cancers. Because cancers are caused by mutations in multiple genes and abnormalities in multiple signaling pathways, synthetic lethality for a specific tumor suppressor gene or oncogene is likely cell context-dependent. Delineation of the mechanisms underlying synthetic lethality and identification of treatment response biomarkers will be critical for the success of synthetic lethality anticancer therapy.

  3. Anticancer Properties of Capsaicin Against Human Cancer.

    PubMed

    Clark, Ruth; Lee, Seong-Ho

    2016-03-01

    There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities.

  4. Glutamic acid as anticancer agent: An overview.

    PubMed

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  5. Osteoresorptive arsenic intoxication.

    PubMed

    Dani, Sergio Ulhoa

    2013-04-01

    A 47-year-old woman consulted her dermatologist complaining whole body dermatitis, urticaria and irritating bullous eruptions on the plantar and side surfaces of her feet. She had had multiple hypopigmented spots on her skin since her early adulthood. The patient was treated with topical medication without significant improvement of symptoms. One year later she suffered a myocardial infarction, accompanied by refractory anaemia. At the age of 49, a breast cancer was diagnosed and shortly thereafter her last menstruation occurred. At age 50years, upon complaint of weight loss despite normal food intake, Hashimoto thyroiditis with latent hyperthyroidism, vitamin D insufficiency with secondary hyperparathyroidism, and poikilocytic anaemia with anisochromia, hypochromia, anisocytosis, elliptocytes, drepanocytes, dacryocytes, acanthocytes, echinocytes, schizocytes, stomatocytes and target cells were diagnosed. The osteodensitometric and laboratory examinations revealed osteoporosis with sustained elevation of urinary Dipyridinolin-crosslinks (u-Dpd), and urinary arsenic (u-As) of 500μg/l (equivalent to 0.5 parts per million-ppm, 2.5μg/mg creatinine/dl, u-As: Phosphate of 26μg/mmol; the estimated bone As:P and As/kg body weight were 500μg/g and 11.3mg/kg, respectively). Thalassemia, immunoglobinopathy and iron deficiency were excluded. Supplementation with oral vitamin D and calcium, and antiresorptive therapy with intravenous zolendronate normalised the u-Dpd, significantly decreased the urinary arsenic concentration, and cured the anemia and the urticaria. A diagnosis of osteoresorptive arsenic intoxication (ORAI) was established. PMID:23337042

  6. Arsenic Exposure and Prevalence of the Varicella Zoster Virus in the United States: NHANES (2003–2004 and 2009–2010)

    PubMed Central

    Cardenas, Andres; Smit, Ellen; Houseman, E. Andres; Kerkvliet, Nancy I.; Bethel, Jeffrey W.

    2015-01-01

    Background Arsenic is an immunotoxicant. Clinical reports observe the reactivation of varicella zoster virus (VZV) in people who have recovered from arsenic poisoning and in patients with acute promyelocytic leukemia that have been treated with arsenic trioxide. Objective We evaluated the association between arsenic and the seroprevalence of VZV IgG antibody in a representative sample of the U.S. population. Methods We analyzed data from 3,348 participants of the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and 2009–2010 pooled survey cycles. Participants were eligible if they were 6–49 years of age with information on both VZV IgG and urinary arsenic concentrations. We used two measures of total urinary arsenic (TUA): TUA1 was defined as the sum of arsenite, arsenate, monomethylarsonic acid, and dimethylarsinic acid, and TUA2 was defined as total urinary arsenic minus arsenobetaine and arsenocholine. Results The overall weighted seronegative prevalence of VZV was 2.2% for the pooled NHANES sample. The geometric means of TUA1 and TUA2 were 6.57 μg/L and 5.64 μg/L, respectively. After adjusting for age, sex, race, income, creatinine, and survey cycle, odds ratios for a negative VZV IgG result in association with 1-unit increases in natural log-transformed (ln)-TUA1 and ln-TUA2 were 1.87 (95% CI: 1.03, 3.44) and 1.40 (95% CI: 1.0, 1.97), respectively. Conclusions In this cross-sectional analysis, urinary arsenic was inversely associated with VZV IgG seroprevalence in the U.S. population. This finding is in accordance with clinical observations of zoster virus reactivation from high doses of arsenic. Additional studies are needed to confirm the association and evaluate causal mechanisms. Citation Cardenas A, Smit E, Houseman EA, Kerkvliet NI, Bethel JW, Kile ML. 2015. Arsenic exposure and prevalence of the varicella zoster virus in the United States: NHANES (2003–2004 and 2009–2010). Environ Health Perspect 123:590–596;

  7. Targeted anticancer therapy: overexpressed receptors and nanotechnology.

    PubMed

    Akhtar, Mohd Javed; Ahamed, Maqusood; Alhadlaq, Hisham A; Alrokayan, Salman A; Kumar, Sudhir

    2014-09-25

    Targeted delivery of anticancer drugs to cancer cells and tissues is a promising field due to its potential to spare unaffected cells and tissues, but it has been a major challenge to achieve success in these therapeutic approaches. Several innovative approaches to targeted drug delivery have been devised based on available knowledge in cancer biology and on technological advancements. To achieve the desired selectivity of drug delivery, nanotechnology has enabled researchers to design nanoparticles (NPs) to incorporate anticancer drugs and act as nanocarriers. Recently, many receptor molecules known to be overexpressed in cancer have been explored as docking sites for the targeting of anticancer drugs. In principle, anticancer drugs can be concentrated specifically in cancer cells and tissues by conjugating drug-containing nanocarriers with ligands against these receptors. Several mechanisms can be employed to induce triggered drug release in response to either endogenous trigger or exogenous trigger so that the anticancer drug is only released upon reaching and preferentially accumulating in the tumor tissue. This review focuses on overexpressed receptors exploited in targeting drugs to cancerous tissues and the tumor microenvironment. We briefly evaluate the structure and function of these receptor molecules, emphasizing the elegant mechanisms by which certain characteristics of cancer can be exploited in cancer treatment. After this discussion of receptors, we review their respective ligands and then the anticancer drugs delivered by nanotechnology in preclinical models of cancer. Ligand-functionalized nanocarriers have delivered significantly higher amounts of anticancer drugs in many in vitro and in vivo models of cancer compared to cancer models lacking such receptors or drug carrying nanocarriers devoid of ligand. This increased concentration of anticancer drug in the tumor site enabled by nanotechnology could have a major impact on the efficiency of cancer

  8. Microbial responses to environmental arsenic.

    PubMed

    Páez-Espino, David; Tamames, Javier; de Lorenzo, Víctor; Cánovas, David

    2009-02-01

    Microorganisms have evolved dynamic mechanisms for facing the toxicity of arsenic in the environment. In this sense, arsenic speciation and mobility is also affected by the microbial metabolism that participates in the biogeochemical cycle of the element. The ars operon constitutes the most ubiquitous and important scheme of arsenic tolerance in bacteria. This system mediates the extrusion of arsenite out of the cells. There are also other microbial activities that alter the chemical characteristics of arsenic: some strains are able to oxidize arsenite or reduce arsenate as part of their respiratory processes. These type of microorganisms require membrane associated proteins that transfer electrons from or to arsenic (AoxAB and ArrAB, respectively). Other enzymatic transformations, such as methylation-demethylation reactions, exchange inorganic arsenic into organic forms contributing to its complex environmental turnover. This short review highlights recent studies in ecology, biochemistry and molecular biology of these processes in bacteria, and also provides some examples of genetic engineering for enhanced arsenic accumulation based on phytochelatins or metallothionein-like proteins.

  9. Arsenic induced complete remission in a refractory T-ALL patient with a distinct T-cell clonal evolution without molecular complete remission: A case report

    PubMed Central

    WU, SUIJING; XU, LING; HUANG, XIN; GENG, SUXIA; XU, YAN; CHEN, SHAOHUA; YANG, LIJIAN; WU, XIULI; WENG, JANYU; DU, XIN; LI, YANGQIU

    2016-01-01

    Currently, arsenic trioxide therapy is widely used for the treatment of acute promyelocytic leukemia (APL), relapsed and refractory adult T-cell leukemia/lymphoma and myelodysplastic syndrome. Regarding the broad antitumor activity of arsenic, certain studies have been undertaken to test its efficacy in treating acute T-cell lymphoblastic leukemia (T-ALL) cell lines and patients; however, to the best of our knowledge, no reports document that arsenic is able to induce the remission of T-ALL patients. The present study reports the case of young male patient diagnosed with T-ALL, with no significant response to common chemotherapy regimens, who finally achieved complete remission without minimal residual disease (as detected by flow cytometry) due to arsenic treatment. This result is encouraging, and the present study has shown that malignant TCRαβ+ cell clones can be detected at the molecular level using reverse transcription-polymerase chain reaction (PCR) combined with the GeneScan technique. The result is mainly based on the T-cell receptor (TCR) Vβ1 clone (a 190-base pair PCR product that with the same complementarity determining region 3 length can be detected for all samples collected during various statuses) and on undetectable TCR Vγ subfamily members, at the time of disease diagnosis. It is important to analyze the dynamically changing TCR pool in leukemia patients during therapy. Although the molecular mechanism through which arsenic contributes to malignant clone elimination remains unclear in the case presented, the use of arsenic is expected to be effective for clinically treating refractory and relapsed T-ALL patients. PMID:27313752

  10. Serendipity in anticancer drug discovery.

    PubMed

    Hargrave-Thomas, Emily; Yu, Bo; Reynisson, Jóhannes

    2012-01-10

    It was found that the discovery of 5.8% (84/1437) of all drugs on the market involved serendipity. Of these drugs, 31 (2.2%) were discovered following an incident in the laboratory and 53 (3.7%) were discovered in a clinical setting. In addition, 263 (18.3%) of the pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in total, 24.1% (347/1437) of marketed drugs can be directly traced to serendipitous events confirming the importance of this elusive phenomenon. In the case of anticancer drugs, 35.2% (31/88) can be attributed to a serendipitous event, which is somewhat larger than for all drugs. The therapeutic field that has benefited the most from serendipity are central nervous system active drugs reflecting the difficulty in designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of the diseases of the mind. PMID:22247822

  11. Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water

    EPA Science Inventory

    Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated ars...

  12. Enhanced coagulation for arsenic removal

    SciTech Connect

    Cheng, R.C.; Liang, S.; Wang, H.C.; Beuhler, M.D. )

    1994-09-01

    The possible use of enhanced coagulation for arsenic removal was examined at the facilities of a California utility in 1992 and 1993. The tests were conducted at bench, pilot, and demonstration scales, with two source waters. Alum and ferric chloride, with cationic polymer, were investigated at various influence arsenic concentrations. The investigators concluded that for the source waters tested, enhanced coagulation could be effective for arsenic removal and that less ferric chloride than alum, on a weight basis, is needed to achieve the same removal.

  13. Correlation of electrochromic properties and oxidation states in nanocrystalline tungsten trioxide.

    PubMed

    Darmawi, S; Burkhardt, S; Leichtweiss, T; Weber, D A; Wenzel, S; Janek, J; Elm, M T; Klar, P J

    2015-06-28

    Although tungsten trioxide (WO3) has been extensively studied since its electrochromic properties were first discovered, the mechanism responsible for the coloration or bleaching effect is still disputed. New insights into the coloration mechanism of electrochromic, nanocrystalline WO3 are provided in this paper by studying thin WO3 films combining the electrochemical and spectroscopic techniques. By employing in situ UV-Vis transmission spectroscopy at a fixed spectral band pass during electrochemical experiments, such as cyclic voltammetry, a two-step insertion process for both protons and lithium ions is identified, of which one step exhibits a significantly higher coloration efficiency than the other. To obtain a better understanding of the insertion process AxWO3 (A = H, Li,…) thin films were studied at different stages of intercalation using UV-Vis and X-ray photoelectron spectroscopy. The results show that the first step of the intercalation process represents the reduction from initial W(6+) to W(5+) and the second step the reduction of W(5+) to W(4+). We found that the blue coloration of this nanocrystalline tungsten trioxide is mainly due to the presence of W(4+) rather than that of W(5+). PMID:26018838

  14. Use of Mineral Trioxide Aggregate in Surgical and Conventional Endodontics: A Report of Five Cases

    PubMed Central

    Goswami, Mridula

    2013-01-01

    ABSTRACT Facial trauma that results in fractured, displaced or lost teeth can have significant negative functional, esthetic and psychological effects on children. An acute dental trauma may imply impact to the hard dental tissues and damage to the pulp and periodontium, ultimately leading to partial or total pulp necrosis and/or root resorption. Apexification is a commonly used procedure for treating and preserving immature permanent teeth that have lost pulp vitality. Immature teeth undergoing apexification were earlier filled with calcium hydroxide paste for the purpose of disinfection and induction of an apical calcific barrier. However, certain drawbacks led to the use of mineral trioxide aggregate (MTA) to fill the apical end without the need for calcific barrier formation. This article demonstrates the use of MTA as an apical barrier material for root-end closure in the permanent teeth of five patients. How to cite this article: Gupta S, Goswami M. Use of Mineral Trioxide Aggregate in Surgical and Conventional Endodontics: A Report of Five Cases. Int J Clin Pediatr Dent 2013;6(2): 134-139. PMID:25206209

  15. Arsenic behavior in newly drilled wells

    USGS Publications Warehouse

    Kim, M.-J.; Nriagu, J.; Haack, S.

    2003-01-01

    In the present paper, inorganic arsenic species and chemical parameters in groundwater were determined to investigate the factors related to the distribution of arsenic species and their dissolution from rock into groundwater. For the study, groundwater and core samples were taken at different depths of two newly drilled wells in Huron and Lapeer Counties, Michigan. Results show that total arsenic concentrations in the core samples varied, ranging from 0.8 to 70.7 mg/kg. Iron concentration in rock was about 1800 times higher than that of arsenic, and there was no correlation between arsenic and iron occurrences in the rock samples. Arsenic concentrations in groundwater ranged from <1 to 171 ??g/l. The arsenic concentration in groundwater depended on the amount of arsenic in aquifer rocks, and as well decreased with increasing depth. Over 90% of arsenic existed in the form of As(III), implying that the groundwater systems were in the reduced condition. The results such as high ferrous ion, low redox potential and low dissolved oxygen supported the observed arsenic species distribution. There was no noticeable difference in the total arsenic concentration and arsenic species ratio between unfiltered and filtered (0.45 ??m) waters, indicating that the particulate form of arsenic was negligible in the groundwater samples. There were correlations between water sampling depth and chemical parameters, and between arsenic concentration and chemical parameters, however, the trends were not always consistent in both wells. ?? 2003 Elsevier Science Ltd. All rights reserved.

  16. Arsenic in water treatment.

    SciTech Connect

    Siegel, Malcolm Dean

    2004-12-01

    Sandia National Laboratories (SNL) is collaborating with the Awwa Research Foundation (AwwaRF) and WERC (A Consortium for Environmental Education and Technology Development) in a program for the development and testing of innovative technologies that have the potential to substantially reduce the costs associated with arsenic removal from drinking water. Sandia National Laboratories will administer contracts placed with AwwaRF and WERC to carry out bench scale studies and economic analyses/outreach activities, respectively. The elements of the AwwaRF program include (1) identification of new technologies, (2) proof-of-concept laboratory studies and, (3) a research program that will meet the other needs of small utilities by providing solutions to small utilities so that they may successfully meet the new arsenic MCL. WERC's activities will include development of an economic analysis tool for Pilot Scale Demonstrations and development of educational training and technical assistance tools. The objective of the Sandia Program is the field demonstration testing of innovative technologies. The primary deliverables of the Sandia program will be engineering analyses of candidate technologies; these will be contained in preliminary reports and final analysis reports. Projected scale-up costs will be generated using a cost model provided by WERC or another suitable model.

  17. The charge and discharge behavior of molybdenum trioxide electrodes in lithium perchlorate-propylene carbonate electrolyte. Technical report

    SciTech Connect

    Hunger, H.F.; Ellison, J.E.

    1980-07-01

    The anodic and cathodic behavior of molybdenum trioxide electrodes in various states of lithiation was investigated in 1M LiClO/sub 4/-PC electrolytes at room temperature. A comparison was made between the anodic and cathodic rate capabilities of the electrodes. From cycling experiments at various depths of discharge, cycle life data were obtained. Problems observed after deep discharges are discussed.

  18. 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.

  19. Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

    PubMed

    Li, S G; Xu, S Z; Niu, Q; Ding, Y S; Pang, L J; Ma, R L; Jing, M X; Wang, K; Ma, X M; Feng, G L; Liu, J M; Zhang, X F; Xiang, H L; Li, F

    2016-05-01

    This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p < 0.01, respectively) in ATO-treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p < 0.01, respectively). The groups treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p < 0.01). Mice treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

  20. Establishment and characterization of an arsenic-sensitive monoblastic leukaemia cell line (SigM5).

    PubMed

    Walter, R; Schoedon, G; Bächli, E; Betts, D R; Hossle, J P; Calandra, T; Joller-Jemelka, H I; Fehr, J; Schaffner, A

    2000-05-01

    Few human monoblastic cell lines have been characterized to date. We have established the SigM5 cell line from a patient with acute monoblastic leukaemia (FAB M5a). Original leukaemic cells had a karyotype of 47,XY,+8, whereas the cell line showed a stemline clone of 81,XX,Y,Y,1,4,6,7,+8,+8,9,10,10,11,13,16,19[cp], with a minor sideline also present. Cytochemical staining was strongly positive with alpha-naphthylbutyrate acetate esterase, particulate positive with Sudan black and weakly positive for myeloperoxidase. Cells were positive for CD13, CD15, CD18, CD23, CD33, CD38, CD45, CD68 and myeloperoxidase. CD14 expression was 3-15%. SigM5 constitutively secreted interleukin (IL)-2, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, ferritin, lysozyme, N-elastase and neopterin upon stimulation with interferon (IFN)-gamma. Cells expressed the proinflammatory mediator macrophage migration inhibitory factor (MIF). All NADPH oxidase subunits were constitutively present, but nitroblue tetrazolium reduction was only detectable upon activation with IFN-gamma. SigM5 monoblasts were sensitive to arsenic trioxide (As2O3) previously not described to induce apoptosis in monoblastic cells. Differing considerably in morphology, immunophenotype and sensitivity to arsenics from the widely used cell lines U937, HL-60 and THP-1, SigM5 is a new monoblastic cell line useful for studying leukaemogenesis, monocyte differentiation and tumour cell susceptibility to arsenic compounds.

  1. [Arsenic as an environmental problem].

    PubMed

    Jensen, K

    2000-12-01

    Chronic exposure to arsenic through drinking water is known in different continents. Arsenic compounds from disintegrating rock may be solubilized after reduction by organic material, and harmful concentrations of arsenic may be found in surface water as well as in water from drilled wells. Because of well drilling since the sixties in the Ganges delta numerous millions of people have been exposed to toxic amounts, and hundreds of thousands demonstrate signs of chronic poisoning. A changed water technology and chemical precipitation of arsenic in the drinking water can reduce the size of the problem, but the late sequelae i.e. malignant disease are incalculable. Indications for antidotal treatment of exposed individuals have not yet been outlined.

  2. Groundwater arsenic contamination throughout China.

    PubMed

    Rodríguez-Lado, Luis; Sun, Guifan; Berg, Michael; Zhang, Qiang; Xue, Hanbin; Zheng, Quanmei; Johnson, C Annette

    2013-08-23

    Arsenic-contaminated groundwater used for drinking in China is a health threat that was first recognized in the 1960s. However, because of the sheer size of the country, millions of groundwater wells remain to be tested in order to determine the magnitude of the problem. We developed a statistical risk model that classifies safe and unsafe areas with respect to geogenic arsenic contamination in China, using the threshold of 10 micrograms per liter, the World Health Organization guideline and current Chinese standard for drinking water. We estimate that 19.6 million people are at risk of being affected by the consumption of arsenic-contaminated groundwater. Although the results must be confirmed with additional field measurements, our risk model identifies numerous arsenic-affected areas and highlights the potential magnitude of this health threat in China.

  3. THE PATHWAY OF ARSENIC METABLISM

    EPA Science Inventory

    The Pathway of Arsenic Methylation

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

    Understanding ...

  4. Arsenic removal by ferric chloride

    SciTech Connect

    Hering, J.G.; Chen, P.Y.; Wilkie, J.A.; Elimelech, M.; Liang, S.

    1996-04-01

    Bench-scale studies were conducted in model freshwater systems to investigate how various parameters affected arsenic removal during coagulation with ferric chloride and arsenic adsorption onto preformed hydrous ferric oxide. Parameters included arsenic oxidation state and initial concentration, coagulant dosage or adsorbent concentration, pH, and the presence of co-occurring inorganic solutes. Comparison of coagulation and adsorption experiments and of experimental results with predictions based on surface complexation modeling demonstrated that adsorption is an important (though not the sole) mechanism governing arsenic removal during coagulation. Under comparable conditions, better removal was observed with arsenic(V) [As(V)] than with arsenic(III) [As(III)] in both coagulation and adsorption experiments. Below neutral pH values, As(III) removal-adsorption was significantly decreased in the presence of sulfate, whereas only a slight decrease in As(V) removal-adsorption was observed. At high pH, removal-adsorption of As(V) was increased in the presence of calcium. Removal of As(V) during coagulation with ferric chloride is both more efficient and less sensitive than that of As(III) to variations in source water composition.

  5. Arsenic Toxicity in Male Reproduction and Development.

    PubMed

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-12-01

    Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children's health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity. PMID:26973968

  6. Arsenic Toxicity in Male Reproduction and Development.

    PubMed

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-12-01

    Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children's health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity.

  7. Arsenic Toxicity to Juvenile Fish: Effects of Exposure Route, Arsenic Speciation, and Fish Species

    EPA Science Inventory

    Arsenic toxicity to juvenile rainbow trout and fathead minnows was evaluated in 28-day tests using both dietborne and waterborne exposures, both inorganic and organic arsenic species, and both a live diet and an arsenic-spiked pellet diet. Effects of inorganic arsenic on rainbow...

  8. Approaches to Increase Arsenic Awareness in Bangladesh: An Evaluation of an Arsenic Education Program

    ERIC Educational Resources Information Center

    George, Christine Marie; Factor-Litvak, Pam; Khan, Khalid; Islam, Tariqul; Singha, Ashit; Moon-Howard, Joyce; van Geen, Alexander; Graziano, Joseph H.

    2013-01-01

    The objective of this study was to design and evaluate a household-level arsenic education and well water arsenic testing intervention to increase arsenic awareness in Bangladesh. The authors randomly selected 1,000 study respondents located in 20 villages in Singair, Bangladesh. The main outcome was the change in knowledge of arsenic from…

  9. Arsenic carcinogenesis in the skin.

    PubMed

    Yu, Hsin-Su; Liao, Wei-Ting; Chai, Chee-Yin

    2006-09-01

    Chronic arsenic poisoning is a world public health issue. Long-term exposure to inorganic arsenic (As) from drinking water has been documented to induce cancers in lung, urinary bladder, kidney, liver and skin in a dose-response relationship. Oxidative stress, chromosomal abnormality and altered growth factors are possible modes of action in arsenic carcinogenesis. Arsenic tends to accumulate in the skin. Skin hyperpigmentation and hyperkeratosis have long been known to be the hallmark signs of chronic As exposure. There are significant associations between these dermatological lesions and risk of skin cancer. The most common arsenic-induced skin cancers are Bowen's disease (carcinoma in situ), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Arsenic-induced Bowen's disease (As-BD) is able to transform into invasive BCC and SCC. Individuals with As-BD are considered for more aggressive cancer screening in the lung and urinary bladder. As-BD provides an excellent model for studying the early stages of chemical carcinogenesis in human beings. Arsenic exposure is associated with G2/M cell cycle arrest and DNA aneuploidy in both cultured keratinocytes and As-BD lesions. These cellular abnormalities relate to the p53 dysfunction induced by arsenic. The characteristic clinical figures of arsenic-induced skin cancer are: (i) occurrence on sun-protected areas of the body; (ii) multiple and recrudescent lesions. Both As and UVB are able to induce skin cancer. Arsenic treatment enhances the cytotoxicity, mutagenicity and clastogenicity of UV in mammalian cells. Both As and UVB induce apoptosis in keratinocytes by caspase-9 and caspase-8 signaling, respectively. Combined UVB and As treatments resulted in the antiproliferative and proapoptotic effects by stimulating both caspase pathways in the keratinocytes. UVB irradiation inhibited mutant p53 and ki-67 expression, as well as increased in the number of apoptotic cells in As-BD lesions which resulted in an

  10. Effect of organic matter amendment, arsenic amendment and water management regime on rice grain arsenic species.

    PubMed

    Norton, Gareth J; Adomako, Eureka E; Deacon, Claire M; Carey, Anne-Marie; Price, Adam H; Meharg, Andrew A

    2013-06-01

    Arsenic accumulation in rice grain has been identified as a major problem in some regions of Asia. A study was conducted to investigate the effect of increased organic matter in the soil on the release of arsenic into soil pore water and accumulation of arsenic species within rice grain. It was observed that high concentrations of soil arsenic and organic matter caused a reduction in plant growth and delayed flowering time. Total grain arsenic accumulation was higher in the plants grown in high soil arsenic in combination with high organic matter, with an increase in the percentage of organic arsenic species observed. The results indicate that the application of organic matter should be done with caution in paddy soils which have high soil arsenic, as this may lead to an increase in accumulation of arsenic within rice grains. Results also confirm that flooding conditions substantially increase grain arsenic. PMID:23466730

  11. Phytoremediation of arsenic contaminated soil by arsenic accumulators: a three year study.

    PubMed

    Raj, Anshita; Singh, Nandita

    2015-03-01

    To investigate whether phytoremediation can remove arsenic from the contaminated area, a study was conducted for three consecutive years to determine the efficiency of Pteris vittata, Adiantum capillus veneris, Christella dentata and Phragmites karka, on arsenic removal from the arsenic contaminated soil. Arsenic concentrations in the soil samples were analysed after harvesting in 2009, 2010 and 2011 at an interval of 6 months. Frond arsenic concentrations were also estimated in all the successive harvests. Fronds resulted in the greatest amount of arsenic removal. Root arsenic concentrations were analysed in the last harvest. Approximately 70 % of arsenic was removed by P. vittata which was recorded as the highest among the four plant species. However, 60 % of arsenic was removed by A. capillus veneris, 55.1 % by C. dentata and 56.1 % by P. karka of arsenic was removed from the contaminated soil in 3 years. PMID:25666567

  12. Locating and estimating air emissions from sources of arsenic and arsenic compounds. Final report

    SciTech Connect

    1998-06-01

    This document describes the properties of arsenic and arsenic compounds as air pollutants, defines production and use patterns, identifies source categories of air emissions, and provides emission factors. Arsenic is emitted as an air pollutant from external combustion boilers, municipal and hazardous waste incineration, primary copper and zinc smelting, glass manufacturing, copper ore mining, and primary and secondary lead smelting. Emissions of arsenic from these activities are due to the presence of trace amounts of arsenic in fuels and materials being processed. In such cases, the emissions may be quite variable because the trace presence of arsenic is not constant. Arsenic emissions also occur from agricultural chemical production and application, and also from metal processing due to the use of arsenic in these activities. In addition to the arsenic source information, information is provided that specifies how individual sources of arsenic may be tested to quantify air emissions.

  13. Effect of organic matter amendment, arsenic amendment and water management regime on rice grain arsenic species.

    PubMed

    Norton, Gareth J; Adomako, Eureka E; Deacon, Claire M; Carey, Anne-Marie; Price, Adam H; Meharg, Andrew A

    2013-06-01

    Arsenic accumulation in rice grain has been identified as a major problem in some regions of Asia. A study was conducted to investigate the effect of increased organic matter in the soil on the release of arsenic into soil pore water and accumulation of arsenic species within rice grain. It was observed that high concentrations of soil arsenic and organic matter caused a reduction in plant growth and delayed flowering time. Total grain arsenic accumulation was higher in the plants grown in high soil arsenic in combination with high organic matter, with an increase in the percentage of organic arsenic species observed. The results indicate that the application of organic matter should be done with caution in paddy soils which have high soil arsenic, as this may lead to an increase in accumulation of arsenic within rice grains. Results also confirm that flooding conditions substantially increase grain arsenic.

  14. Analysis of six heavy metals in Ortho mineral trioxide aggregate and ProRoot mineral trioxide aggregate by inductively coupled plasma-optical emission spectrometry.

    PubMed

    Kum, Kee-Yeon; Zhu, Qiang; Safavi, Kamran; Gu, Yu; Bae, Kwang-Shik; Chang, Seok Woo

    2013-12-01

    Ortho mineral trioxide aggregate (MTA) is a mineral aggregate newly developed for perforation repair, root end filling and pulp capping. The aim of this study was to investigate the levels of cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni) and zinc (Zn) in Ortho MTA and ProRoot MTA. A total of 0.2 g of each MTA was digested using a mixture of hydrochloric and nitric acids and filtered. Six heavy metals in the resulting filtrates were analyzed by inductively coupled plasma-optical emission spectrometry (n = 5). The results were statistically analyzed using the Mann-Whitney U-test. The concentrations of Cd, Cu, Fe, Mn, Ni and Zn in Ortho MTA were 0.10, 7.73, 49.51, 2.58, 0.82 and 10.09 p.p.m., respectively. The concentrations of Cd, Cu, Fe, Mn, Ni and Zn in ProRoot MTA were 0.16, 9.38, 1438.11, 74.51, 18.98 and 4.05 p.p.m., respectively. In conclusion, Ortho MTA had lower levels of Cd, Cu, Fe, Mn and Ni than ProRoot MTA. PMID:24279659

  15. Removing arsenic from copper smelter gases

    NASA Astrophysics Data System (ADS)

    Dalewski, Frank

    1999-09-01

    The pyrometallurgical processing of nonferrous minerals found in association with sulfur and arsenic generates arsenic-bearing SO2 gases. Effective process gas cleaning presents technical problems due to the high volatility of the As2O3 compound and the elevated dew point of the sulfur-trioxidecontaining SO2 gas. Critical factors for gascleaning technology selection pertaining to technical feasibility, economic acceptability, and environmental compatibility are the arsenic-to-sulfur ratio in the feed material, the operating parameters of the pyrometallurgical and gas cooling process, the admissible arsenic concentration of the SO2 gas after arsenic elimination, and the most suitable form of the arsenic-bearing output material. Depending on these factors, the bulk of the arsenic can be eliminated from the process gas in concentrated form according to either the dry or wet method, after which final arsenic removal from the process gas to below the required admissible level must take place in a wet electrostatic precipitator.

  16. Production of selenium-72 and arsenic-72

    DOEpatents

    Phillips, Dennis R.

    1993-01-01

    Methods for producing selenium-72, separating it from its daughter isotope arsenic-72, and generating multiple portions of a solution containing arsenic-72 from a reusable parent substance comprised of selenium-72.

  17. Production of selenium-72 and arsenic-72

    DOEpatents

    Phillips, D.R.

    1993-04-20

    Methods are described for producing selenium-72, separating it from its daughter isotope arsenic-72, and generating multiple portions of a solution containing arsenic-72 from a reusable parent substance comprised of selenium-72.

  18. Arsenic in the aetiology of cancer.

    PubMed

    Tapio, Soile; Grosche, Bernd

    2006-06-01

    Arsenic, one of the most significant hazards in the environment affecting millions of people around the world, is associated with several diseases including cancers of skin, lung, urinary bladder, kidney and liver. Groundwater contamination by arsenic is the main route of exposure. Inhalation of airborne arsenic or arsenic-contaminated dust is a common health problem in many ore mines. This review deals with the questions raised in the epidemiological studies such as the dose-response relationship, putative confounders and synergistic effects, and methods evaluating arsenic exposure. Furthermore, it describes the metabolic pathways of arsenic, and its biological modes of action. The role of arsenic in the development of cancer is elucidated in the context of combined epidemiological and biological studies. However, further analyses by means of molecular epidemiology are needed to improve the understanding of cancer aetiology induced by arsenic.

  19. Arsenic Speciation in Groundwater: Role of Thioanions

    EPA Science Inventory

    The behavior of arsenic in groundwater environments is fundamentally linked to its speciation. Understanding arsenic speciation is important because chemical speciation impacts reactivity, bioavailability, toxicity, and transport and fate processes. In aerobic environments arsen...

  20. Anticancer activity of Carica papaya: a review.

    PubMed

    Nguyen, Thao T T; Shaw, Paul N; Parat, Marie-Odile; Hewavitharana, Amitha K

    2013-01-01

    Carica papaya is widely cultivated in tropical and subtropical countries and is used as food as well as traditional medicine to treat a range of diseases. Increasing anecdotal reports of its effects in cancer treatment and prevention, with many successful cases, have warranted that these pharmacological properties be scientifically validated. A bibliographic search was conducted using the key words "papaya", "anticancer", and "antitumor" along with cross-referencing. No clinical or animal cancer studies were identified and only seven in vitro cell-culture-based studies were reported; these indicate that C. papaya extracts may alter the growth of several types of cancer cell lines. However, many studies focused on specific compounds in papaya and reported bioactivity including anticancer effects. This review summarizes the results of extract-based or specific compound-based investigations and emphasizes the aspects that warrant future research to explore the bioactives in C. papaya for their anticancer activities.

  1. Development of anticancer agents: wizardry with osmium.

    PubMed

    Hanif, Muhammad; Babak, Maria V; Hartinger, Christian G

    2014-10-01

    Platinum compounds are one of the pillars of modern cancer chemotherapy. The apparent disadvantages of existing chemotherapeutics have led to the development of novel anticancer agents with alternative modes of action. Many complexes of the heavy metal osmium (Os) are potent growth inhibitors of human cancer cells and are active in vivo, often superior or comparable to cisplatin, as the benchmark metal-based anticancer agent, or clinically tested ruthenium (Ru) drug candidates. Depending on the choice of ligand system, osmium compounds exhibit diverse modes of action, including redox activation, DNA targeting or inhibition of protein kinases. In this review, we highlight recent advances in the development of osmium anticancer drug candidates and discuss their cellular mechanisms of action.

  2. Development of anticancer agents: wizardry with osmium.

    PubMed

    Hanif, Muhammad; Babak, Maria V; Hartinger, Christian G

    2014-10-01

    Platinum compounds are one of the pillars of modern cancer chemotherapy. The apparent disadvantages of existing chemotherapeutics have led to the development of novel anticancer agents with alternative modes of action. Many complexes of the heavy metal osmium (Os) are potent growth inhibitors of human cancer cells and are active in vivo, often superior or comparable to cisplatin, as the benchmark metal-based anticancer agent, or clinically tested ruthenium (Ru) drug candidates. Depending on the choice of ligand system, osmium compounds exhibit diverse modes of action, including redox activation, DNA targeting or inhibition of protein kinases. In this review, we highlight recent advances in the development of osmium anticancer drug candidates and discuss their cellular mechanisms of action. PMID:24955838

  3. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry).

    PubMed

    Zhao, Tiejun; Sun, Qiang; Marques, Maud; Witcher, Michael

    2015-01-01

    There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Phyllanthus emblica can account for some of the anticancer activity, but clearly other mechanisms are equally important. Herein, we provide a brief overview of the evidence supporting anticancer activity of Indian Gooseberry extracts, suggest possible mechanisms for these actions, and provide future directions that might be taken to translate these findings clinically.

  4. Acute arsenic poisoning in two siblings.

    PubMed

    Lai, Melisa W; Boyer, Edward W; Kleinman, Monica E; Rodig, Nancy M; Ewald, Michele Burns

    2005-07-01

    We report a case series of acute arsenic poisoning of 2 siblings, a 4-month-old male infant and his 2-year-old sister. Each child ingested solubilized inorganic arsenic from an outdated pesticide that was misidentified as spring water. The 4-month-old child ingested a dose of arsenic that was lethal despite extraordinary attempts at arsenic removal, including chelation therapy, extracorporeal membrane oxygenation, exchange transfusion, and hemodialysis. The 2-year-old fared well with conventional therapy.

  5. Nonsurgical Endodontic Retreatment of Advanced Inflammatory External Root Resorption Using Mineral Trioxide Aggregate Obturation

    PubMed Central

    Utneja, Shivani; Garg, Gaurav; Arora, Shipra; Talwar, Sangeeta

    2012-01-01

    Inflammatory external root resorption is one of the major complications after traumatic dental injury. In this case report, we describe treatment of a maxillary central incisor affected by severe, perforating external root resorption. An 18-year-old patient presented with a previously traumatized, root-filled maxillary central incisor associated with pain and sinus tract. Radiographic examination revealed periradicular lesion involving pathologic resorption of the apical region of the root and lateral root surface both mesially and distally. After removal of the root canal filling, the tooth was disinfected with intracanal triple antibiotic paste for 2 weeks. The antibiotic dressing was then removed, and the entire root canal was filled with mineral trioxide aggregate. The endodontic access cavity was restored with composite resin. After 18 months, significant osseous healing of the periradicular region and lateral periodontium had occurred with arrest of external root resorption, and no clinical symptoms were apparent. PMID:23304567

  6. Conservative Management of Unset Mineral Trioxide Aggregate Root-End Filling: A Case Report

    PubMed Central

    Parirokh, Masoud; Farzaneh, Sedigheh; Hallajmofrad, Ali Reza

    2016-01-01

    This case report presents conservative management of unset mineral trioxide aggregate (MTA) after being placed as a root-end filling material following periapical surgery. Periapical surgery was indicated for a maxillary lateral incisor of a 15-year-old male due to persistent exudate and a large periapical lesion. During surgery Angelus MTA was placed as root-end filling. The next session it was noticed that MTA had failed to completely set. In an orthograde approach, calcium-enriched mixture (CEM) cement was used to obturate the root canal space. The patient was followed up for 27 months and did not exhibit any clinical signs and symptoms. Radiographic images showed complete healing of the lesion. PMID:27471540

  7. Apexification with calcium hydroxide and mineral trioxide aggregate: Report of two cases

    PubMed Central

    Gawthaman, Murugesan; Vinodh, Selvaraj; Mathian, Veerabadhran Mahesh; Vijayaraghavan, Rangasamy; Karunakaran, Ramachandran

    2013-01-01

    The completion of root development and closure of the apex occurs up to 3 years after the eruption of the tooth. The treatment of pulpal injury during this period provides a significant challenge for the clinician. The importance of careful case assessment and accurate pulpal diagnosis in the treatment of immature teeth with pulpal injury cannot be overemphasized. The treatment of choice for necrotic teeth is apexification, which is induction of apical closure to produce more favorable conditions for conventional root canal filling. The most commonly advocated medicament is calcium hydroxide, although recently considerable interest has been expressed in the use of mineral trioxide aggregate (MTA). We report a case series wherein calcium hydroxide and MTA were used successfully for one step apexification in teeth with open apex. PMID:23956590

  8. Enhancement of the antimicrobial properties of orthorhombic molybdenum trioxide by thermal induced fracturing of the hydrates.

    PubMed

    Shafaei, Shahram; Van Opdenbosch, Daniel; Fey, Tobias; Koch, Marcus; Kraus, Tobias; Guggenbichler, Josef Peter; Zollfrank, Cordt

    2016-01-01

    The oxides of the transition metal molybdenum exhibit excellent antimicrobial properties. We present the preparation of molybdenum trioxide dihydrate (MoO3 × 2H2O) by an acidification method and demonstrate the thermal phase development and morphological evolution during and after calcination from 25 °C to 600 °C. The thermal dehydration of the material was found to proceed in two steps. Microbiological roll-on tests using Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were performed and exceptional antimicrobial activities were determined for anhydrous samples with orthorhombic lattice symmetry and a large specific surface area. The increase in the specific surface area is due to crack formation and to the loss of the hydrate water after calcination at 300 °C. The results support the proposed antimicrobial mechanism for transition metal oxides, which based on a local acidity increase as a consequence of the augmented specific surface area.

  9. Enhancement of the antimicrobial properties of orthorhombic molybdenum trioxide by thermal induced fracturing of the hydrates.

    PubMed

    Shafaei, Shahram; Van Opdenbosch, Daniel; Fey, Tobias; Koch, Marcus; Kraus, Tobias; Guggenbichler, Josef Peter; Zollfrank, Cordt

    2016-01-01

    The oxides of the transition metal molybdenum exhibit excellent antimicrobial properties. We present the preparation of molybdenum trioxide dihydrate (MoO3 × 2H2O) by an acidification method and demonstrate the thermal phase development and morphological evolution during and after calcination from 25 °C to 600 °C. The thermal dehydration of the material was found to proceed in two steps. Microbiological roll-on tests using Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were performed and exceptional antimicrobial activities were determined for anhydrous samples with orthorhombic lattice symmetry and a large specific surface area. The increase in the specific surface area is due to crack formation and to the loss of the hydrate water after calcination at 300 °C. The results support the proposed antimicrobial mechanism for transition metal oxides, which based on a local acidity increase as a consequence of the augmented specific surface area. PMID:26478404

  10. Chemical and morphological characteristics of mineral trioxide aggregate and Portland cements.

    PubMed

    Khan, Shahbaz; Kaleem, Muhammad; Fareed, Muhammad Amber; Habib, Amir; Iqbal, Kefi; Aslam, Ayesha; Ud Din, Shahab

    2016-01-01

    The purpose of this study was to investigate the chemical composition and particle morphology of white mineral trioxide aggregate (WMTA) and two white Portland cements (CEM 1 and CEM 2). Compositional analysis was performed by energy dispersive X-ray spectroscopy, X-ray fluorescence spectrometry and X-ray diffraction whereas, morphological characteristics were analyzed by scanning electron microscope and Laser scattering particle size distribution analyzer. The elemental composition of WMTA, CEM 1 and CEM 2 were similar except for the presence of higher amounts of bismuth in WMTA. Calcium oxide and silicon oxide constitute the major portion of the three materials whereas, tricalcium silicate was detected as the major mineral phase. The particle size distribution and morphology of WMTA was finer compared to CEM 1 and CEM 2. The three tested materials had relatively similar chemical composition and irregular particle morphologies.

  11. Tungsten Trioxide (WO3) Nanoparticles as a New Anode Material for Sodium-Ion Batteries.

    PubMed

    Santhosha, A L; Das, Shyamal K; Bhattacharyya, Aninda J

    2016-04-01

    Tungsten trioxide (WO3) is investigated for the first time as an anode material for sodium-ion batteries. Pristine WO3 displays a discharge potential plateau at 1 V and exhibits a 1st discharge cycle sodium storage capacity of 640 mAh g-1. Electronic wiring of WO3 with graphene oxide (GO, 1% by weight) led to a significant increase in the storage capacity and cyclability of WO3. As a result, the discharge capacity of 1% GO-WO3 is enhanced to 927 mAh g-1 in the 1st discharge cycle. The electrochemical intercalation of Na in to WO3 and (1%) GO-WO3 as obtained from galvanostatic charge/discharge cycling is also supported by cyclic voltammetry. PMID:27451776

  12. Analysis of mineral trioxide aggregate surface when set in the presence of fetal bovine serum.

    PubMed

    Tingey, Mark C; Bush, Peter; Levine, Ming Shih

    2008-01-01

    Understanding the chemical and physical characteristics of set mineral trioxide aggregate (MTA) surface can provide insight into its bioactivity. The purpose of this study was to describe the surface chemistry and morphology of gray and white MTA set in the presence of fetal bovine serum (FBS). Eight MTA blocks were prepared: four set in the presence of water and four in FBS. The surface morphologic characteristics were studied via scanning electron microscopy. The surface chemical composition of the set cement was investigated by energy dispersive x-ray spectroscopy and x-ray fluorescence. No difference was found between gray and white MTA when set in the same solution. However, MTA/FBS and MTA/water present differing surface morphology and chemical distributions. When set in FBS, MTA's surface had a homogenous distribution of chemicals and a relatively smooth globular appearance. MTA/water's surface was biphasic, containing large hexagonal crystalline plates composed of calcium embedded in a pool of globular crystals.

  13. Management of External Invasive Cervical Resorption Tooth with Mineral Trioxide Aggregate: A Case Report

    PubMed Central

    Ikhar, Anuja; Thakur, Nikita; Patel, Aditya; Bhede, Rohan; Patil, Pranav; Gupta, Surbhi

    2013-01-01

    Invasive cervical resorption is entirely uncommon entities and the etiology is poorly understood. A 19 year old patient presented with fractured upper left central incisor and sinus tract opening on the distobuccal aspect in cervical region. Radiographic examination shows irregular radiolucency over the coronal one-third and it extended externally towards the external invasive resorption. After sectional obturation, the defect was accessed surgically. The resorption area was chemomechanically debrided using irrigant solution. Fibre post placement using flowable composite resin and Mineral Trioxide Aggregate (MTA) was used to fill the resorptive defect, and the coronal access was temporarily sealed. Composite restoration was subsequently replaced with ceramic crown after 4 years. Radiographs at 1 and 4 years showed adequate repair of the resorption and endodontic success. Clinically and radiographically the tooth was asymptomatic, and no periodontal pocket was found after a 4-year followup. PMID:23476658

  14. Magnetic polymer nanospheres for anticancer drug targeting

    NASA Astrophysics Data System (ADS)

    Juríková, A.; Csach, K.; Koneracká, M.; Závišová, V.; Múčková, M.; Tomašovičová, N.; Lancz, G.; Kopčanský, P.; Timko, M.; Miškuf, J.

    2010-01-01

    Poly(D,L-lactide-co-glycolide) polymer (PLGA) nanospheres loaded with biocom-patible magnetic fluid as a magnetic carrier and anticancer drug Taxol were prepared by the modified nanoprecipitation method with size of 200-250 nm in diameter. The PLGA polymer was utilized as a capsulation material due to its biodegradability and biocompatibility. Taxol as an important anticancer drug was chosen for its significant role against a wide range of tumours. Thermal properties of the drug-polymer system were characterized using thermal analysis methods. It was determined the solubility of Taxol in PLGA nanospheres. Magnetic properties investigated using SQUID magnetometry showed superparamagnetism of the prepared magnetic polymer nanospheres.

  15. Studies with Myrtus communis L.: Anticancer properties.

    PubMed

    Ogur, Recai

    2014-01-01

    Myrtus communis (MC) L. is a well-known Mediterranean plant with important cultural significance in this region. In ancient times, MC was accepted as a symbol of immortality. Maybe due to this belief, it is used during cemetery visits in some regions. Although it is a well-known plant in cosmetics, and there is a lot of studies about its different medical properties, anticancer studies performed using its different extracts or oils are not so much, but increasing. We collected these anticancer property-related studies in this review. PMID:26401362

  16. Arsenic intoxication associated with tubulointerstitial nephritis.

    PubMed

    Prasad, G V; Rossi, N F

    1995-08-01

    Arsenic poisoning is an often unrecognized cause of renal insufficiency. We report a case of tubulointerstitial nephritis associated with an elevated urinary arsenic concentration. Removal of the putative source of arsenic resulted in symptomatic improvement, resolution of abnormal abdominal radiographs, and stabilization of renal function. This case emphasizes the importance of heavy metal screening in patients with multisystem complaints and tubulointerstitial nephritis.

  17. Arsenic Metabolism and Distribution in Developing Organisms

    EPA Science Inventory

    A growing body of evidence suggests that exposure to inorganic arsenic during early life has long term adverse effects. The extent of exposure to inorganic arsenic and its methylated metabolites in utero is determined not only by the rates of formation and transfer of arsenicals...

  18. SPECIATION OF ARSENIC IN EXPOSURE ASSESSMENT MATRICES

    EPA Science Inventory

    The speciaton of arsenic in water, food and urine are analytical capabilities which are an essential part in arsenic risk assessment. The cancer risk associated with arsenic has been the driving force in generating the analytical research in each of these matrices. This presentat...

  19. TYPES OF ARSENIC AND TREATMENT OPTIONS

    EPA Science Inventory

    Presentation will discuss the state-of-the-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...

  20. 21 CFR 556.60 - Arsenic.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Arsenic. 556.60 Section 556.60 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND... New Animal Drugs § 556.60 Arsenic. Tolerances for total residues of combined arsenic (calculated as...

  1. 21 CFR 556.60 - Arsenic.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Arsenic. 556.60 Section 556.60 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND... New Animal Drugs § 556.60 Arsenic. Tolerances for total residues of combined arsenic (calculated as...

  2. 21 CFR 556.60 - Arsenic.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Arsenic. 556.60 Section 556.60 Food and Drugs FOOD... New Animal Drugs § 556.60 Arsenic. (a) (b) Tolerances. The tolerances for total residue of combined arsenic (calculated as As) are: (1) Turkeys—(i) Muscle and eggs: 0.5 parts per million (ppm). (ii)...

  3. Linking Arsenic Metabolism and Toxic Effects

    EPA Science Inventory

    Although arsenic has been long recognized as a toxicant and a carcinogen, the molecular basis for few of its adverse effects are well understood. Like other metalloids, arsenic undergoes extensive metabolism involving oxidation state changes and formation of methyl-arsenic bonds ...

  4. GROUND WATER TREATMENT PROCESSES FOR ARSENIC REMOVAL

    EPA Science Inventory

    In 1975 EPA established a maximum contaminant level (MCL) for arsenic at 0.05 mg/L. In 1996, Congress amended the SDWA and these amendments required that EPA develop an arsenic research strategy and publish a proposal to revise the arsenic MCL by January 2000. The Agency proposed...

  5. Arsenic Exposure and Toxicology: A Historical Perspective

    EPA Science Inventory

    The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, in various forms, has also been used as a pesticide and a ch...

  6. Arsenic - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Arsenic URL of this page: https://medlineplus.gov/languages/arsenic.html Other topics A-Z A B C ... V W XYZ List of All Topics All Arsenic - Multiple Languages To use the sharing features on ...

  7. Comparison of two histopathologic methods for evaluating subcutaneous reaction to mineral trioxide aggregate

    PubMed Central

    Lotfi, Mehrdad; Moradzadeh, Monir; Aghbali, Amirala; Rahimi, Saeed; Saghiri, Mohammadali; Zand, Vahid; Mehdipour, Masoumeh; Ranjkesh, Bahram; Doosti, Sirvan

    2012-01-01

    Objectives: One of the most important factors for suitable materials for pulp therapy is biocompatibility. Two histopathologic methods of Cox and Federation Dentaire International (FDI) were used to evaluate inflammation. In Cox method, density of inflammatory cells, tissue reactions like fibrosis, vascular responses like congestion and fibrin extravasation have been used to evaluate inflammatory reactions. The aim of this study was to compare the accuracy of pathologists’ interpretations using two different methods. Study design: Three pathologists observed the degree of inflammation in 225 histopathologic sections. These sections showed inflammation in subcutaneous connective tissue of rats adjacent to polyethylene tubes, filled with white or gray mineral trioxide aggregate. Empty tubes served as controls. Samples were harvested after 7-, 15-, 30-, 60-, and 90-days. All pathologists examined the sections under a light microscope (Carl Zeiss, Oberkochen, Germany) at ×400 magnifications. Chi-Square test was used to evaluate the difference between inflammation grades when one pathologist used two methods. Cohen’s Kappa value was used to measure agreement of three pathologists to recognize the degrees of inflammations when using one of the methods. Results: There were no significant differences between the two methods when one of the pathologist used these methods to report the degree of inflammation (p=0.054). However, two other pathologists reported significant differences between two methods (p=0.005, p=0.001). In the FDI method, there was an acceptable agreement between first and second, and first and third pathologist in terms of the degree of inflammation, and intermediate agreement existed between the second and third pathologist. With the Cox method, no agreement among the pathologists could be found. Conclusion: The results of three pathologists in terms of rating inflammation with the FDI method showed better agreement than with the Cox method

  8. Synthesis of (-)-arctigenin derivatives and their anticancer activity.

    PubMed

    Gui-Rong, Chen; Li-Ping, Cai; De-Qiang, Dou; Ting-Guo, Kang; Hong-Fu, Li; Fu-Rui, Li; Ning, Jiang

    2012-01-01

    The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin, which was prepared from fructus arctii, showed obvious anticancer activity. The synthesis of four new (-)-arctigenin derivatives and their anticancer bioactivities were examined. The structures of the four new synthetic derivatives were elucidated.

  9. 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

  10. Arsenic intoxication, a hemorheologic view.

    PubMed

    Bollini, A; Huarte, M; Hernández, G; Bazzoni, G; Piehl, L; Mengarelli, G; de Celis, E Rubín; Rasia, M

    2010-01-01

    Arsenic (As) is a toxic semi-metal of wide distribution in nature. People living in regions where drinking water contains large quantities of arsenic, have an unusually high likelihood of developing blood-vessel diseases, but little is known about the mechanisms involved, i.e. the blood rheologic alterations that would contribute to the circulatory obstruction. Erythrocytes are the main target cells for arsenic compounds systemically absorbed and their cell membrane is the first place against the toxic. In this paper we have examined the in vitro effect of arsenic (As(V)) on the rheologic properties of human erythrocytes in relation with membrane fluidity and internal microviscosity. According to our present results, As(V) treatment produces oxidative degradation of membrane lipids and alteration of internal microviscosity. These red blood cells (RBCs) membrane and cytoplasmic structural damage consequently alters RBCs rheologic properties: an alteration of the RBCs discoid shape to stomatocytes, a diminution of erythrocyte deformability and an enhancement of osmotic fragility and cell aggregability. These effects impaired blood fluid behaviour that contribute to obstruct peripheral circulation and provides anemia, both clinic evidences typical of arsenic cronic intoxication.

  11. Groundwater arsenic in Chimaltenango, Guatemala.

    PubMed

    Lotter, Jason T; Lacey, Steven E; Lopez, Ramon; Socoy Set, Genaro; Khodadoust, Amid P; Erdal, Serap

    2014-09-01

    In the Municipality of Chimaltenango, Guatemala, we sampled groundwater for total inorganic arsenic. In total, 42 samples were collected from 27 (43.5%) of the 62 wells in the municipality, with sites chosen to achieve spatial representation throughout the municipality. Samples were collected from household faucets used for drinking water, and sent to the USA for analysis. The only site found to have a concentration above the 10 μg/L World Health Organization provisional guideline for arsenic in drinking water was Cerro Alto, where the average concentration was 47.5 μg/L. A health risk assessment based on the arsenic levels found in Cerro Alto showed an increase in noncarcinogenic and carcinogenic risks for residents as a result of consuming groundwater as their primary drinking water source. Using data from the US Geological Survey and our global positioning system data of the sample locations, we found Cerro Alto to be the only site sampled within the tertiary volcanic rock layer, a known source of naturally occurring arsenic. Recommendations were made to reduce the levels of arsenic found in the community's drinking water so that the health risks can be managed.

  12. Stress proteins induced by arsenic.

    PubMed

    Del Razo, L M; Quintanilla-Vega, B; Brambila-Colombres, E; Calderón-Aranda, E S; Manno, M; Albores, A

    2001-12-01

    The elevated expression of stress proteins is considered to be a universal response to adverse conditions, representing a potential mechanism of cellular defense against disease and a potential target for novel therapeutics. Exposure to arsenicals either in vitro or in vivo in a variety of model systems has been shown to cause the induction of a number of the major stress protein families such as heat shock proteins (Hsp). Among them are members with low molecular weight, such as metallotionein and ubiquitin, as well as ones with masses of 27, 32, 60, 70, 90, and 110 kDa. In most of the cases, the induction of stress proteins depends on the capacity of the arsenical to reach the target, its valence, and the type of exposure, arsenite being the biggest inducer of most Hsp in several organs and systems. Hsp induction is a rapid dose-dependent response (1-8 h) to the acute exposure to arsenite. Thus, the stress response appears to be useful to monitor the sublethal toxicity resulting from a single exposure to arsenite. The present paper offers a critical review of the capacity of arsenicals to modulate the expression and/or accumulation of stress proteins. The physiological consequences of the arsenic-induced stress and its usefulness in monitoring effects resulting from arsenic exposure in humans and other organisms are discussed.

  13. Arsenic, Anaerobes, and Autotrophy.

    NASA Astrophysics Data System (ADS)

    Oremland, R. S.

    2008-12-01

    That microbes have resistance to the toxic arsenic oxyanions arsenite [As(III)] and arsenate [As(V)] has been recognized for some time. More recently it was shown that certain prokaryotes can demonstrate As- dependent growth by conserving the energy gained from the aerobic oxidation of As(III) to As(V), or from the reduction of As(V) to As(III) under anaerobic conditions. During the course of our field studies of two alkaline, hypersaline soda lakes (Mono Lake and Searles Lake, CA) we have discovered several new anaerobic chemo- and photo-autotrophic bacteria that can center their energy gain around the redox reactions between As(III) and As(V). Alkalilimnicola ehrlichii, isolated from the water column of Mono Lake is a nitrate-respiring, As(III)-oxidizing chemoautotroph of the gamma-proteobacteria that has a highly flexible metabolism. It can function either as a facultative anaerobe or as a chemo-autotroph, or as a heterotroph (Hoeft et al., 2007). In contrast, strain MLMS-1 of the delta-proteobacteria was also isolated from Mono Lake, but to date is the first example of an obligate As(V)-respirer that is also an obligate chemo-autotroph, gaining its energy via the oxidation of sulfide to sulfate (Hoeft et al., 2004). Strain SLAS-1, isolated from salt-saturated Searles Lake is a member of the Halananerobiales, and can either grow as a heterotroph (lactate e-donor) or chemo- autotroph (sulfide e-donor) while respiring As(V). The fact that it can achieve this feat at salt-saturation (~ 340 g/L) makes it a true extremophile (Oremland et. al., 2005). Finally, strain PHS-1 isolated from a hot spring on Paoha island in Mono Lake is the first example of a photosynthetic bacterium of the gamma- proteobacteria able to link its growth to As(III)-dependent anoxygenic photosynthesis (Kulp et al., 2008). These novel microbes give us new insights into the evolution of arsenic-based metabolism and their role in the biogeochemical cycling of this toxic element. Hoeft, S.E., et

  14. Analysis of the transcriptional regulation of cancer-related genes by aberrant DNA methylation of the cis-regulation sites in the promoter region during hepatocyte carcinogenesis caused by arsenic

    PubMed Central

    Miao, Zhuang; Wu, Lin; Lu, Ming; Meng, Xianzhi; Gao, Bo; Qiao, Xin; Zhang, Weihui; Xue, Dongbo

    2015-01-01

    Liver is the major organ for arsenic methylation metabolism and may be the potential target of arsenic-induced cancer. In this study, normal human liver cell was treated with arsenic trioxide, and detected using DNA methylation microarray. Some oncogenes, tumor suppressor genes, transcription factors (TF), and tumor-associated genes (TAG) that have aberrant DNA methylation have been identified. However, simple functional studies of genes adjacent to aberrant methylation sites cannot well reflect the regulatory relationship between DNA methylation and gene transcription during the pathogenesis of arsenic-induced liver cancer, whereas a further analysis of the cis-regulatory elements and their trans-acting factors adjacent to DNA methylation can more precisely reflect the relationship between them. MYC and MAX (MYC associated factor X) were found to participating cell cycle through a bioinformatics analysis. Additionally, it was found that the hypomethylation of cis-regulatory sites in the MYC promoter region and the hypermethylation of cis-regulatory sites in the MAX promoter region result in the up-regulation of MYC mRNA expression and the down-regulation of MAX mRNA, which increased the hepatocyte carcinogenesis tendency. PMID:26046465

  15. Cell Death Signaling and Anticancer Therapy

    PubMed Central

    Galluzzi, Lorenzo; Vitale, Ilio; Vacchelli, Erika; Kroemer, Guido

    2011-01-01

    For a long time, it was commonly believed that efficient anticancer regimens would either trigger the apoptotic demise of tumor cells or induce a permanent arrest in the G1 phase of the cell cycle, i.e., senescence. The recent discovery that necrosis can occur in a regulated fashion and the increasingly more precise characterization of the underlying molecular mechanisms have raised great interest, as non-apoptotic pathways might be instrumental to circumvent the resistance of cancer cells to conventional, pro-apoptotic therapeutic regimens. Moreover, it has been shown that some anticancer regimens engage lethal signaling cascades that can ignite multiple oncosuppressive mechanisms, including apoptosis, necrosis, and senescence. Among these signaling pathways is mitotic catastrophe, whose role as a bona fide cell death mechanism has recently been reconsidered. Thus, anticancer regimens get ever more sophisticated, and often distinct strategies are combined to maximize efficacy and minimize side effects. In this review, we will discuss the importance of apoptosis, necrosis, and mitotic catastrophe in the response of tumor cells to the most common clinically employed and experimental anticancer agents. PMID:22655227

  16. Mineral resource of the month: arsenic

    USGS Publications Warehouse

    Brooks, William E.

    2008-01-01

    Arsenic has a long and varied history: Although it was not isolated as an element until the 13th century, it was known to the ancient Chinese, Egyptians and Greeks in compound form in the minerals arsenopyrite, realgar and orpiment. In the 1400s, “Scheele’s Green” was first used as an arsenic pigment in wallpaper, and leached arsenic from wallpaper may have contributed to Napoleon’s death in 1821. The 1940s play and later movie, Arsenic and Old Lace, dramatizes the metal’s more sinister role. Arsenic continues to be an important mineral commodity with many modern applications.

  17. Merkel cell carcinoma and chronic arsenicism.

    PubMed

    Lien, H C; Tsai, T F; Lee, Y Y; Hsiao, C H

    1999-10-01

    Arsenic is a well-documented human carcinogen. Bowen's disease, squamous cell carcinoma, and basal cell carcinoma are the most common skin cancers found in patients exposed to arsenic over the long term. Merkel cell carcinoma has been documented in Taiwanese patients who resided in an endemic area of black foot disease, another condition found in patients with chronic arsenicism. We collected all cases of Merkel cell carcinoma diagnosed at two medical centers in Taiwan (N = 11) to find a possible association between chronic arsenicism and Merkel cell carcinoma. In our study 6 of the 11 patients were residents of the endemic areas for chronic arsenicism.

  18. The studying of washing of arsenic and sulfur from coals having different ranges of arsenic contents

    USGS Publications Warehouse

    Wang, M.; Song, D.; Zheng, B.; Finkelman, R.B.; ,

    2008-01-01

    To study the effectiveness of washing in removal of arsenic and sulfur from coals with different ranges of arsenic concentration, coal was divided into three groups on the basis of arsenic content: 0-5.5 mg/kg, 5.5 mg/kg-8.00 mg/kg, and over 8.00 mg/kg. The result shows that the arsenic in coals with higher arsenic content occurs mainly in an inorganic state and can be relatively easily removed. Arsenic removal is very difficult and less complete when the arsenic content is lower than 5.5 mg/kg because most of this arsenic is in an organic state. There is no relationship between washing rate of total sulfur and arsenic content, but the relationship between the washing rate of total sulfur and percent of organic sulfur is very strong. ?? 2008 New York Academy of Sciences.

  19. The studying of washing of arsenic and sulfur from coals having different ranges of arsenic contents

    SciTech Connect

    Mingshi Wang; Dangyu Song; Baoshan Zheng; R.B. Finkelman

    2008-10-15

    To study the effectiveness of washing in removal of arsenic and sulfur from coals with different ranges of arsenic concentration, coal was divided into three groups on the basis of arsenic content: 0-5.5 mg/kg, 5.5 mg/kg-8.00 mg/kg, and over 8.00 mg/kg. The result shows that the arsenic in coals with higher arsenic content occurs mainly in an inorganic state and can be relatively easily removed. Arsenic removal is very difficult and less complete when the arsenic content is lower than 5.5 mg/kg because most of this arsenic is in an organic state. There is no relationship between washing rate of total sulfur and arsenic content, but the relationship between the washing rate of total sulfur and percent of organic sulfur is very strong.

  20. Arsenic contamination in food-chain: transfer of arsenic into food materials through groundwater irrigation.

    PubMed

    Huq, S M Imamul; Joardar, J C; Parvin, S; Correll, Ray; Naidu, Ravi

    2006-09-01

    Arsenic contamination in groundwater in Bangladesh has become an additional concern vis-à-vis its use for irrigation purposes. Even if arsenic-safe drinking-water is assured, the question of irrigating soils with arsenic-laden groundwater will continue for years to come. Immediate attention should be given to assess the possibility of accumulating arsenic in soils through irrigation-water and its subsequent entry into the food-chain through various food crops and fodders. With this possibility in mind, arsenic content of 2,500 water, soil and vegetable samples from arsenic-affected and arsenic-unaffected areas were analyzed during 1999-2004. Other sources of foods and fodders were also analyzed. Irrigating a rice field with groundwater containing 0.55 mg/L of arsenic with a water requirement of 1,000 mm results in an estimated addition of 5.5 kg of arsenic per ha per annum. Concentration of arsenic as high as 80 mg per kg of soil was found in an area receiving arsenic-contaminated irrigation. A comparison of results from affected and unaffected areas revealed that some commonly-grown vegetables, which would usually be suitable as good sources of nourishment, accumulate substantially-elevated amounts of arsenic. For example, more than 150 mg/kg of arsenic has been found to be accumulated in arum (kochu) vegetable. Implications of arsenic ingested in vegetables and other food materials are discussed in the paper. PMID:17366772