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Sample records for exposure arsenic induced

  1. Environmental Arsenic Exposure and Microbiota in Induced Sputum

    Directory of Open Access Journals (Sweden)

    Allison G. White

    2014-02-01

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

  2. Arsenic exposure induces the Warburg effect in cultured human cells

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    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T., E-mail: klimecki@pharmacy.arizona.edu

    2013-08-15

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect.

  3. Arsenic exposure induces the Warburg effect in cultured human cells

    International Nuclear Information System (INIS)

    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T.

    2013-01-01

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect

  4. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats

    International Nuclear Information System (INIS)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

    2017-01-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. - Highlights: • Arsenic exposure has been associated with a number of adverse health effects. • The molecular mechanisms involved in arsenic-induced cardiotoxicity remain unclear. • Differential proteins were identified in arsenic-exposed rat heart by proteomics. • Arsenic induces heart toxicity through the Akt/p38 MAPK signaling pathway. - Label-free quantitative proteomic analysis of rat heart reveals putative mechanisms and biomarkers for arsenic-induced cardiotoxicity.

  5. Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB.

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    Bao-Fei Sun

    Full Text Available High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g. was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF and phosphorylated cAMP-response element binding protein (pCREB in the CA1 and dentate gyrus areas (DG of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus.

  6. Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism

    Science.gov (United States)

    Tyler, Christina R.; Solomon, Benjamin R.; Ulibarri, Adam L.; Allan, Andrea M.

    2014-01-01

    Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic–pituitary–adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism. PMID:24952232

  7. Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan

    International Nuclear Information System (INIS)

    Chen, C.-J.; Hsu, L.-I; Wang, C.-H.

    2005-01-01

    Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis are for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic included blood levels of reactive oxidants and anti-oxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress

  8. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats

    DEFF Research Database (Denmark)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen

    2017-01-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative...... proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33...... proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb...

  9. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

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    Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  10. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats.

    Science.gov (United States)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

    2017-10-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Arsenic induced apoptosis in rat liver following repeated 60 days exposure

    International Nuclear Information System (INIS)

    Bashir, Somia; Sharma, Yukti; Irshad, M.; Nag, T.C.; Tiwari, Monica; Kabra, M.; Dogra, T.D.

    2006-01-01

    Background: Accumulation of the wide spread environmental toxin arsenic in liver results in hepatotoxcity. Exposure to arsenite and other arsenicals has been previously shown to induce apoptosis in certain tumor cell lines at low (1-3 μM) concentration. Aim: The present study was focused to elucidate the role of free radicals in arsenic toxicity and to investigate the nature of in vivo sodium arsenite induced cell death in liver. Methods: Male wistar rats were exposed to arsenite at three different doses of 0.05, 2.5 and 5 mg/l for 60 days. Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant activity in liver. Histopathological examination of liver was carried out by light and transmission electron microscopy. Analysis of DNA fragmentation by gel electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy-nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to qualify and quantify apoptosis. Results: A significant increase in cytochrome-P450 and lipid peroxidation accompanied with a significant alteration in the activity of many of the antioxidants was observed, all suggestive of arsenic induced oxidative stress. Histopathological examination under light and transmission electron microscope suggested a combination of ongoing necrosis and apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern. Conclusion: Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis

  12. Perturbations in immune responses induced by concurrent subchronic exposure to arsenic and endosulfan

    International Nuclear Information System (INIS)

    Aggarwal, Manoj; Naraharisetti, Suresh Babu; Dandapat, S.; Degen, G.H.; Malik, J.K.

    2008-01-01

    The metalloid arsenic and the chlorinated insecticide endosulfan are common environmental contaminants. Humans, animals, and birds are exposed to these chemicals through water and food. Although health effects due to either arsenic or endosulfan exposure are documented, the toxicological impact of co-exposure to these environmental pollutants is unpredictable and unknown. The present study was undertaken to assess whether concurrent exposure to arsenic and endosulfan induces significant alterations in immunological functions. Day-old chicks were exposed to 3.7 ppm of arsenic via drinking water and to 30 ppm of endosulfan-mixed feed either individually or concurrently for up to 60 days. All the chicks were vaccinated with Ranikhet disease virus (F-strain; RD-F) on days 1 and 30. During the course of study and at term, parameters of cellular and humoral immunity were determined. None of the treatments altered the absolute body weight or body weight gain, except arsenic significantly reduced weight gain on day 60. Absolute, but not the relative, weights of spleen, thymus and bursa of Fabricius were significantly reduced in all the treatment groups. The metalloid and insecticide combination significantly depressed the ability of peripheral blood and splenic lymphocytes to proliferate in response to antigen RD-F and mitogen Con A. The delayed type hypersensitivity response to 2,4-dinitro-1-chlorobenzene or to PHA-P was also significantly decreased. Nitric oxide production by RD-F or lipopolysaccharide-stimulated peripheral blood and splenic mononuclear cells was significantly suppressed following concurrent exposure to arsenic and endosulfan. Furthermore, the combined exposure also decreased the antibody response to RD-F. The suppression of cellular and humoral immune responses was also evident following administration of individual compounds, and it was not exacerbated following concurrent exposure. To our knowledge, this is the first report describing the suppression

  13. Environmental Source of Arsenic Exposure

    OpenAIRE

    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 ...

  14. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

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    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  15. Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB

    OpenAIRE

    Sun, Bao-Fei; Wang, Qing-Qing; Yu, Zi-Jiang; Yu, Yan; Xiao, Chao-Lun; Kang, Chao-Sheng; Ge, Guo; Linghu, Yan; Zhu, Jun-De; Li, Yu-Mei; Li, Qiang-Ming; Luo, Shi-Peng; Yang, Dang; Li, Lin; Zhang, Wen-Yan

    2015-01-01

    High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM) of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g.) was administered daily for 12 weeks. We found that arsenic at dos...

  16. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

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    Chia-Yu Chang

    2015-01-01

    Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

  17. Health Effects of Chronic Arsenic Exposure

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    Young-Seoub Hong

    2014-09-01

    Full Text Available Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments.

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

    International Nuclear Information System (INIS)

    Pei, Qiuling; Ma, Ning; Zhang, Jing; Xu, Wenchao; Li, Yong; Ma, Zhifeng; Li, Yunyun; Tian, Fengjie; Zhang, Wenping; Mu, Jinjun; Li, Yuanfei; Wang, Dongxing; Liu, Haifang; Yang, Mimi; Ma, Caifeng; Yun, Fen

    2013-01-01

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

  19. Risk of Erectile Dysfunction Induced by Arsenic Exposure through Well Water Consumption in Taiwan

    Science.gov (United States)

    Hsieh, Fang-I; Hwang, Ti-Sheng; Hsieh, Yi-Chen; Lo, Hsiu-Chiung; Su, Chien-Tien; Hsu, Hui-Shing; Chiou, Hung-Yi; Chen, Chien-Jen

    2008-01-01

    Background Erectile dysfunction (ED) has a profound impact on the quality of life of many men. Many risk factors are associated with ED, such as aging, sex hormone levels, hypertension, cardiovascular diseases, and diabetes mellitus. Arsenic exposure could damage peripheral vessels and increase the risk of cardiovascular disease. However, the relationship between arsenic exposure and ED has seldom been evaluated. Objectives In this study we aimed to investigate whether exposure to arsenic enhances the risk of ED. Methods We recruited 177 males ≥ 50 years of age through health examinations conducted in three hospitals in Taiwan. We used a questionnaire (International Index of Erectile Function-5) to measure the level of erectile function. Sex hormones, including total testosterone and sex hormone–binding globulin, were determined by radioimmunoassay. We used another standardized questionnaire to collect background and behavioral information (e.g., cigarette smoking; alcohol, tea, or coffee drinking; and physical activity). Results The prevalence of ED was greater in the arsenic-endemic area (83.3%) than in the non–arsenic-endemic area (66.7%). Subjects with arsenic exposure > 50 ppb had a significantly higher risk of developing ED than those with exposure ≤ 50 ppb, after adjusting for age, cigarette smoking, diabetes mellitus, hypertension, and cardiovascular disease [odds ratio (OR) = 3.4]. Results also showed that the risk of developing severe ED was drastically enhanced by arsenic exposure (OR = 7.5), after adjusting for free testosterone and traditional risk factors of ED. Conclusions Results suggested that chronic arsenic exposure has a negative impact on erectile function. PMID:18414639

  20. Environmental source of arsenic exposure.

    Science.gov (United States)

    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.

  1. Environmental Source of Arsenic Exposure

    Directory of Open Access Journals (Sweden)

    Jin-Yong Chung

    2014-09-01

    Full Text Available 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.

  2. Resveratrol, a Natural Antioxidant, Has a Protective Effect on Liver Injury Induced by Inorganic Arsenic Exposure

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    Zhigang Zhang

    2014-01-01

    Full Text Available Resveratrol (Rev can ameliorate cytotoxic chemotherapy-induced toxicity and oxidative stress. Arsenic trioxide (As2O3 is a known cytotoxic environmental toxicant and a potent chemotherapeutic agent. However, the mechanisms by which resveratrol protects the liver against the cytotoxic effects of As2O3 are not known. Therefore, in the present study we investigated the mechanisms involved in the action of resveratrol using a cat model in which hepatotoxicity was induced by means of As2O3 treatment. We found that pretreatment with resveratrol, administered using a clinically comparable dose regimen, reversed changes in As2O3-induced morphological and liver parameters and resulted in a significant improvement in hepatic function. Resveratrol treatment also improved the activities of antioxidant enzymes and attenuated As2O3-induced increases in reactive oxygen species and malondialdehyde production. In addition, resveratrol attenuated the As2O3-induced reduction in the ratio of reduced glutathione to oxidized glutathione and the retention of arsenic in liver tissue. These findings provide a better understanding of the mechanisms whereby resveratrol modulates As2O3-induced changes in liver function and tissue morphology. They also provide a stronger rationale for the clinical utilization of resveratrol for the reduction of As2O3-induced hepatotoxicity.

  3. Dietary Arsenic Exposure in Bangladesh

    OpenAIRE

    Kile, Molly L.; Houseman, E. Andres; Breton, Carrie V.; Smith, Thomas; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Christiani, David C.

    2007-01-01

    Background Millions of people in Bangladesh are at risk of chronic arsenic toxicity from drinking contaminated groundwater, but little is known about diet as an additional source of As exposure. Methods We employed a duplicate diet survey to quantify daily As intake in 47 women residing in Pabna, Bangladesh. All samples were analyzed for total As, and a subset of 35 samples were measured for inorganic arsenic (iAs) using inductively coupled plasma mass spectrometry equipped with a dynamic rea...

  4. Arsenic-induced skin lesions among Atacameño people in Northern Chile despite good nutrition and centuries of exposure.

    Science.gov (United States)

    Smith, A H; Arroyo, A P; Mazumder, D N; Kosnett, M J; Hernandez, A L; Beeris, M; Smith, M M; Moore, L E

    2000-07-01

    It has been suggested that the indigenous Atacameño people in Northern Chile might be protected from the health effects of arsenic in drinking water because of many centuries of exposure. Here we report on the first intensive investigation of arsenic-induced skin lesions in this population. We selected 11 families (44 participants) from the village of Chiu Chiu, which is supplied with water containing between 750 and 800 microg/L inorganic arsenic. For comparison, 8 families (31 participants) were also selected from a village where the water contains approximately 10 microg/L inorganic arsenic. After being transported to the nearest city for blind assessment, participants were examined by four physicians with experience in studying arsenic-induced lesions. Four of the six men from the exposed village, who had been drinking the contaminated water for more than 20 years, were diagnosed with skin lesions due to arsenic, but none of the women had definite lesions. A 13-year-old girl had definite skin pigmentation changes due to arsenic, and a 19-year-old boy had both pigmentation changes and keratoses on the palms of his hands and the soles of his feet. Family interviews identified a wide range of fruits and vegetables consumed daily by the affected participants, as well as the weekly intake of red meat and chicken. However, the prevalence of skin lesions among men and children in the small population studied was similar to that reported with corresponding arsenic drinking water concentrations in both Taiwan and West Bengal, India--populations in which extensive malnutrition has been thought to increase susceptibility.

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

    Directory of Open Access Journals (Sweden)

    Robin B. Harris

    2012-03-01

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

    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 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 2 O 3

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

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    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

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

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Fabrizio Bianchi

    2013-04-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2011-08-15

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

  12. Environmental arsenic exposure, selenium and sputum alpha-1 antitrypsin

    DEFF Research Database (Denmark)

    Burgess, Jefferey L; Kurzius-Spencer, Margaret; Poplin, Gerald S

    2014-01-01

    Exposure to arsenic in drinking water is associated with increased respiratory disease. Alpha-1 antitrypsin (AAT) protects the lung against tissue destruction. The objective of this study was to determine whether arsenic exposure is associated with changes in airway AAT concentration and whether...... this relationship is modified by selenium. A total of 55 subjects were evaluated in Ajo and Tucson, Arizona. Tap water and first morning void urine were analyzed for arsenic species, induced sputum for AAT and toenails for selenium and arsenic. Household tap-water arsenic, toenail arsenic and urinary inorganic...... arsenic and metabolites were significantly higher in Ajo (20.6±3.5 μg/l, 0.54±0.77 μg/g and 27.7±21.2 μg/l, respectively) than in Tucson (3.9±2.5 μg/l, 0.16±0.20 μg/g and 13.0±13.8 μg/l, respectively). In multivariable models, urinary monomethylarsonic acid (MMA) was negatively, and toenail selenium...

  13. Studying arsenic trioxide-induced apoptosis of Colo-16 cells with ...

    African Journals Online (AJOL)

    Jane

    2011-10-05

    Oct 5, 2011 ... induced apoptosis at the single cell level. Key words: Two-photon laser scanning microscopy, confocal laser scanning microscopy, human skin squamous carcinoma cells (Colo-16 cells), arsenic trioxide, apoptosis. INTRODUCTION. Although arsenic is poisonous and chronic arsenic exposure from ...

  14. Unfolded Protein Response Signaling and MAP Kinase Pathways Underlie Pathogenesis of Arsenic-induced Cutaneous Inflammation

    OpenAIRE

    Li, Changzhao; Xu, Jianmin; Li, Fugui; Chaudhary, Sandeep C.; Weng, Zhiping; Wen, Jianming; Elmets, Craig A.; Ahsan, Habibul; Athar, Mohammad

    2011-01-01

    Arsenic exposure through drinking water is a major global public health problem and is associated with an enhanced risk of various cancers including skin cancer. In human skin, arsenic induces precancerous melanosis and keratosis, which may progress to basal cell and squamous cell carcinoma. However, the mechanism by which these pathophysiological alterations occur remains elusive. In this study, we showed that sub-chronic arsenic exposure to SKH-1 mice induced unfolded protein response (UPR)...

  15. [Study of relationship between arsenic methylation and skin lesion in a population with long-term high arsenic exposure].

    Science.gov (United States)

    Su, Liqin; Cheng, Yibin; Lin, Shaobin; Wu, Chuanye

    2007-05-01

    To investigate the difference of arsenic metabolism in populations with long-term high arsenic exposure and explore the relationship between arsenic metabolism diversity and skin lesion. 327 residents in an arsenic polluted village were voluntarily enrolled in this study. Questionnaire survey and medical examination were carried out to learn basic information and detect skin lesions. Urinary inorganic and methylated arsenic were speciated by high performance liquid chromatography combined with hydride-generation atomic fluorescence spectrometry. Total arsenic concentration in hair was determined with DDC-Ag method. Hair arsenic content of studied polutions was generally high, but no significant difference were found among the studied four groups. MMA and DMA concentration in urine increased with studied polution age, and were positively related with skin lesion grade. The relative proportion of MMA in serious skin lesion group was significantly higher than in other 3 groups, while DMA/MMA ratio was significantly lower than control and mild group. The relative proportion of MMA was positively related with skin lesion grade, DMA/ MMA ratio was negatively related with skin lesion grade. Males could have higher arsenic cumulation and lower methylation capacity than those of females. The population of above 40 years old may have higher methylation capacity than those of adults below 40yeas old. Smokers and drinkers seemed lower methylation capacity than those of non-smokers and non-drinkers respectively. The methylation of arsenic could affect by several factors, including age gender, smoking and drinking. Arsenic methylation copacity mey be associated with skin lesion induced by arsenic exposure.

  16. EFFECTS OF ARSENIC EXPOSURE IN HUMAN HEALTH

    Directory of Open Access Journals (Sweden)

    Aline Sueli de Lima Rodrigues

    2008-10-01

    Full Text Available In recent years, ingestion of inorganic arsenic from drinking water has emerged as an important public health concern. It enters drinking water supplies from natural deposits in the earth or from agricultural and industrial practices, mainly the mining. The health consequences of chronic arsenic exposure include increased risk for various forms of cancer and numerous pathologic effects, such as cutaneous effects (hyperpigmentation and hyperkeratoses, gastrointestinal effects, vascular effects, diabetes mellitus, and peripheral neuropathy. This way, this study presents through a critical revision of the literature, the more relevant current aspects on the immunological consequences, carcinogenic and resulting genetics of the human intoxication for arsenic. They were identified and analyzed 50 works published on the subject among the years of 1979 and 2008, being used as main sources LILACS-BIREME MEDLINE/Index Medicus, SciELO and PubMed. The specific Arsênio e saúde humana effects of the intoxication for arsenic about the human health are not still completely elucidated. Thus, is possible that this element affects functions still unknown, becoming important the scientificexploration on the subject.

  17. Role of complex organic arsenicals in food in aggregate exposure to arsenic

    Science.gov (United States)

    For much of the world’s population, food is the major source of exposure to arsenic. Exposure to this non-essential metalloid at relatively low levels has been linked to a wide range of adverse health effects. Thus, evaluating foods as sources of exposure to arsenic is important ...

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Xuefeng, E-mail: xuefengr@buffalo.edu [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Gaile, Daniel P. [Department of Biostatistics, School of Public Health and Health Professions, the State University of New York, Buffalo, NY 14214 (United States); Gong, Zhihong [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Qiu, Wenting [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Ge, Yichen [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Olson, James R. [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195 (United States); Wu, Hongmei, E-mail: hongmeiwwu@hotmail.com [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China)

    2015-03-15

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

  20. Environmental exposure to arsenic and chromium in an industrial area

    OpenAIRE

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

    2017-01-01

    Arsenic and chromium are widespread environmental contaminants that affect global health due to their toxicity and carcinogenicity. To date, few studies have investigated exposure to arsenic and chromium in a population residing in a high-risk environmental area. The aim of this study is to evaluate the exposure to arsenic and chromium in the general population with no occupational exposure to these metals, resident in the industrial area of Taranto, Southern Italy, through biological monitor...

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

    International Nuclear Information System (INIS)

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

    2007-01-01

    Exposure to inorganic arsenic in utero in C3H mice produces hepatocellular carcinoma in male offspring when they reach adulthood. To help define the molecular events associated with the fetal onset of arsenic hepatocarcinogenesis, pregnant C3H mice were given drinking water containing 0 (control) or 85 ppm arsenic from day 8 to 18 of gestation. At the end of the arsenic exposure period, male fetal livers were removed and RNA isolated for microarray analysis using 22K oligo chips. Arsenic exposure in utero produced significant (p < 0.001) alterations in expression of 187 genes, with approximately 25% of aberrantly expressed genes related to either estrogen signaling or steroid metabolism. Real-time RT-PCR on selected genes confirmed these changes. Various genes controlled by estrogen, including X-inactive-specific transcript, anterior gradient-2, trefoil factor-1, CRP-ductin, ghrelin, and small proline-rich protein-2A, were dramatically over-expressed. Estrogen-regulated genes including cytokeratin 1-19 and Cyp2a4 were over-expressed, although Cyp3a25 was suppressed. Several genes involved with steroid metabolism also showed remarkable expression changes, including increased expression of 17β-hydroxysteroid dehydrogenase-7 (HSD17β7; involved in estradiol production) and decreased expression of HSD17β5 (involved in testosterone production). The expression of key genes important in methionine metabolism, such as methionine adenosyltransferase-1a, betaine-homocysteine methyltransferase and thioether S-methyltransferase, were suppressed. Thus, exposure of mouse fetus to inorganic arsenic during a critical period in development significantly alters the expression of various genes encoding estrogen signaling and steroid or methionine metabolism. These alterations could disrupt genetic programming at the very early life stage, which could impact tumor formation much later in adulthood

  2. A review of the epidemiologic literature on the role of environmental arsenic exposure and cardiovascular diseases

    International Nuclear Information System (INIS)

    Wang, C.-H.; Hsiao, C.K.; Chen, C.-L.; Hsu, L.-I; Chiou, H.-Y.; Chen, S.-Y.; Hsueh, Y.-M.; Wu, M.-M.; Chen, C.-J.

    2007-01-01

    Cardiovascular disease is the leading cause of mortality worldwide. Arsenic is a ubiquitous metalloid in the crust of the earth. Chronic arsenic poisoning is becoming an emerging epidemic in Asia. Epidemiological studies have shown that chronic arsenic poisoning through ingestion of arsenic-contaminated water is associated with various cardiovascular diseases in dose-response relationships. These cardiovascular disorders include carotid atherosclerosis detected by ultrasonography, impaired microcirculation, prolonged QT interval and increased QT dispersion in electrocardiography, and clinical outcomes such as hypertension, blackfoot disease (a unique peripheral vascular disease endemic in southwestern Taiwan), coronary artery disease and cerebral infarction. Chronic arsenic poisoning is an independent risk factor for cardiovascular disease. The adverse cardiovascular effects of long-term arsenic exposure may be persistent and/or irreversible. Arsenic-induced cardiovascular diseases in human population may result from the interaction among genetic, environment and nutritional factors. The major adverse cardiovascular effect of chronic arsenic poisoning has been established qualitatively and quantitatively in the high arsenic exposure areas, but the low-dose effect of arsenic on cardiovascular diseases remains to be explored. Cardiovascular death is the major cause of mortality worldwide, and a small increased risk may imply a large quantity of excess mortality

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

    Science.gov (United States)

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

    2017-05-01

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

  4. Biological monitoring of arsenic exposure of gallium arsenide- and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, H.; Takahashi, K.; Mashiko, M.; Yamamura, Y. (St. Marianna Univ. School of Medicine, Kawasaki (Japan))

    1989-11-01

    In an attempt to establish a method for biological monitoring of inorganic arsenic exposure, the chemical species of arsenic were measured in the urine and hair of gallium arsenide (GaAs) plant and copper smelter workers. Determination of urinary inorganic arsenic concentration proved sensitive enough to monitor the low-level inorganic arsenic exposure of the GaAs plant workers. The urinary inorganic arsenic concentration in the copper smelter workers was far higher than that of a control group and was associated with high urinary concentrations of the inorganic arsenic metabolites, methylarsonic acid (MAA) and dimethylarsinic acid (DMAA). The results established a method for exposure level-dependent biological monitoring of inorganic arsenic exposure. Low-level exposures could be monitored only by determining urinary inorganic arsenic concentration. High-level exposures clearly produced an increased urinary inorganic arsenic concentration, with an increased sum of urinary concentrations of inorganic arsenic and its metabolites (inorganic arsenic + MAA + DMAA). The determination of urinary arsenobetaine proved to determine specifically the seafood-derived arsenic, allowing this arsenic to be distinguished clearly from the arsenic from occupational exposure. Monitoring arsenic exposure by determining the arsenic in the hair appeared to be of value only when used for environmental monitoring of arsenic contamination rather than for biological monitoring.

  5. Napoleon Bonaparte's exposure to arsenic during 1816.

    Science.gov (United States)

    Leslie, A C; Smith, H

    1978-12-11

    Analysis of hair from Napoleon showed that he was exposed to considerable amounts of arsenic during 1816. The distribution pattern of the arsenic in the hair is similar to that found after the daily ingestion of excessive amounts of arsenic.

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

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  8. Specific histone modification responds to arsenic-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Lu [Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou (China); Li, Jun [Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou (China); Zhan, Zhengbao; Chen, Liping; Li, Daochuan; Bai, Qing; Gao, Chen; Li, Jie; Zeng, Xiaowen; He, Zhini; Wang, Shan; Xiao, Yongmei [Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou (China); Chen, Wen, E-mail: chenwen@mail.sysu.edu.cn [Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou (China); Zhang, Aihua, E-mail: aihuagzykd@163.com [Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou (China)

    2016-07-01

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

  9. Specific histone modification responds to arsenic-induced oxidative stress

    International Nuclear Information System (INIS)

    Ma, Lu; Li, Jun; Zhan, Zhengbao; Chen, Liping; Li, Daochuan; Bai, Qing; Gao, Chen; Li, Jie; Zeng, Xiaowen; He, Zhini; Wang, Shan; Xiao, Yongmei; Chen, Wen; Zhang, Aihua

    2016-01-01

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

  10. Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism

    International Nuclear Information System (INIS)

    Cheng, Tain-Junn; Chuu, Jiunn-Jye; Chang, Chia-Yu; Tsai, Wan-Chen; Chen, Kuan-Jung; Guo, How-Ran

    2011-01-01

    Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor β (LXRβ) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXRβ activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXRβ and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element. - Highlights: → Arsenic causes cardiovascular and cerebrovascular diseases through atherosclerosis. → Arsenic may promote atherosclerosis with transient increase in HSP 70 and hs

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

    Science.gov (United States)

    Ahmed, Mubashir; Fatmi, Zafar; Ali, Arif

    2014-01-01

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

  12. MDI Biological Laboratory Arsenic Summit: Approaches to Limiting Human Exposure to Arsenic

    OpenAIRE

    Stanton, Bruce A.

    2015-01-01

    This report is the outcome of the meeting: “Environmental and Human Health Consequences of Arsenic”, held at the MDI Biological Laboratory in Salisbury Cove, Maine, August 13–15, 2014. Human exposure to arsenic represents a significant health problem worldwide that requires immediate attention according to the World Health Organization (WHO). One billion people are exposed to arsenic in food and more than 200 million people ingest arsenic via drinking water at concentrations greater than inte...

  13. GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth

    Directory of Open Access Journals (Sweden)

    Emily F. Winterbottom

    2015-06-01

    Full Text Available Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health.

  14. Neurotoxicity induced by arsenic in Gallus Gallus: Regulation of oxidative stress and heat shock protein response.

    Science.gov (United States)

    Zhao, Panpan; Guo, Ying; Zhang, Wen; Chai, Hongliang; Xing, Houjuan; Xing, Mingwei

    2017-01-01

    Arsenic, a naturally occurring heavy metal pollutant, is one of the functioning risk factors for neurological toxicity in humans. However, little is known about the effects of arsenic on the nervous system of Gallus Gallus. To investigate whether arsenic induce neurotoxicity and influence the oxidative stress and heat shock proteins (Hsps) response in chickens, seventy-two 1-day-old male Hy-line chickens were treated with different doses of arsenic trioxide (As 2 O 3 ). The histological changes, antioxidant enzyme activity, and the expressions of Hsps were detected. Results showed slightly histology changes were obvious in the brain tissues exposure to arsenic. The activities of Glutathione peroxidase (GSH-Px) and catalase (CAT) were decreased compared to the control, whereas the malondialdehyde (MDA) content was increased gradually along with increase in diet-arsenic. The mRNA levels of Hsps and protein expressions of Hsp60 and Hsp70 were up-regulated. These results suggested that sub-chronic exposure to arsenic induced neurotoxicity in chickens. Arsenic exposure disturbed the balance of oxidants and antioxidants. Increased heat shock response tried to protect chicken brain tissues from tissues damage caused by oxidative stress. The mechanisms of neurotoxicity induced by arsenic include oxidative stress and heat shock protein response in chicken brain tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Ameliorative effects of selenium on arsenic-induced cytotoxicity in PC12 cells via modulating autophagy/apoptosis.

    Science.gov (United States)

    Rahman, Md Mostafizur; Uson-Lopez, Rachael A; Sikder, Md Tajuddin; Tan, Gongxun; Hosokawa, Toshiyuki; Saito, Takeshi; Kurasaki, Masaaki

    2018-04-01

    Arsenic is well known toxicant responsible for human diseases including cancers. On the other hand, selenium is an essential trace element with significant chemopreventive effects, anticancer potentials and antioxidant properties. Although previous studies have reported antagonism/synergism between arsenic and selenium in biological systems, the biomolecular mechanism/s is still inconclusive. Therefore, to elucidate the molecular phenomena in cellular level, we hypothesized that co-exposure of selenium with arsenic may have suppressive effects on arsenic-induced cytotoxicity. We found that selenium in co-exposure with arsenic increases cell viability, and suppresses oxidative stress induced by arsenic in PC12 cells. Consequently, DNA fragmentation due to arsenic exposure was also reduced by arsenic and selenium co-exposure. Furthermore, western blot analyses revealed that simultaneous exposure of both metals significantly inhibited autophagy which further suppressed apoptosis through positively regulation of key proteins; p-mTOR, p-Akt, p-Foxo1A, p62, and expression of ubiquitin, Bax, Bcl2, NFкB, and caspases 3 and 9, although those are negatively regulated by arsenic. In addition, reverse transcriptase PCR analysis confirmed the involvement of caspase cascade in cell death process induced by arsenic and subsequent inhibition by co-exposure of selenium with arsenic. The cellular accumulation study of arsenic in presence/absence of selenium via inductively coupled plasma mass spectrometry confirmed that selenium effectively retarded the uptake of arsenic in PC12 cells. Finally, these findings imply that selenium is capable to modulate arsenic-induced intrinsic apoptosis pathway via enhancement of mTOR/Akt autophagy signaling pathway through employing antioxidant potentials and through inhibiting the cellular accumulation of arsenic in PC12 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. CHURCHILL COUNTY, NEVADA ARSENIC STUDY: WATER CONSUMPTION AND EXPOSURE BIOMARKERS

    Science.gov (United States)

    The US Environmental Protection Agency is required to reevaluate the Maximum Contaminant Level (MCL) for arsenic in 2006. To provide data for reducing uncertainties in assessing health risks associated with exposure to low levels (<200 g/l) of arsenic, a large scale biomarker st...

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

    International Nuclear Information System (INIS)

    Pu, Y.-S.; Yang, S.-M.; Huang, Y.-K.; Chung, C.-J.; Huang, Steven K.; Chiu, Allen Wen-Hsiang; Yang, M.-H.; Chen, C.-J.; Hsueh, Y.-M.

    2007-01-01

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

  18. The potential biological mechanisms of arsenic-induced diabetes mellitus

    International Nuclear Information System (INIS)

    Tseng, C.-H.

    2004-01-01

    arsenic exposure, oxidative stress is increased and the expression of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) is upregulated. Both of these two cytokines have been well known for their effect on the induction of insulin resistance. Arsenite at physiologically relevant concentration also shows inhibitory effect on the expression of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor important for activating insulin action. Oxidative stress has been suggested as a major pathogenic link to both insulin resistance and β cell dysfunction through mechanisms involving activation of nuclear factor-κB (NF-κB), which is also activated by low levels of arsenic. Although without supportive data, superoxide production induced by arsenic exposure can theoretically impair insulin secretion by interaction with uncoupling protein 2 (UCP2), and oxidative stress can also cause amyloid formation in the pancreas, which could progressively destroy the insulin-secreting β cells. Individual susceptibility with respect to genetics, nutritional status, health status, detoxification capability, interactions with other trace elements, and the existence of other well-recognized risk factors of diabetes mellitus can influence the toxicity of arsenic on organs involved in glucose metabolism and determine the progression of insulin resistance and impaired insulin secretion to a status of persistent hyperglycemia or diabetes mellitus. In conclusions, insulin resistance and β cell dysfunction can be induced by chronic arsenic exposure. These defects may be responsible for arsenic-induced diabetes mellitus, but investigations are required to test this hypothesis

  19. Chronic exposure to low concentration of arsenic is immunotoxic to fish: Role of head kidney macrophages as biomarkers of arsenic toxicity to Clarias batrachus

    International Nuclear Information System (INIS)

    Datta, Soma; Ghosh, Debabrata; Saha, Dhira Rani; Bhattacharaya, Shelley; Mazumder, Shibnath

    2009-01-01

    The present study was aimed at elucidating the effect of chronic low-level arsenic exposure on the head kidney (HK) of Clarias batrachus and at determining the changes in head kidney macrophage (HKM) activity in response to arsenic exposure. Chronic exposure (30 days) to arsenic (As 2 O 3 , 0.50 μM) led to significant increase in arsenic content in the HK accompanied by reduction in both HKM number and head kidney somatic index (HKSI). Arsenic induced HK hypertrophy, reduction in melano-macrophage population and increased hemosiderin accumulation. Transmission electron microscopy of 30 days exposed HKM revealed prominent endoplasmic reticulum, chromatin condensation and loss in structural integrity of nuclear membrane. Head kidney macrophages from exposed fish demonstrated significant levels of superoxide anions but on infection with Aeromonas hydrophila were unable to clear the intracellular bacteria and died. Exposure-challenge experiments with A. hydrophila revealed that chronic exposure to micromolar concentration of arsenic interfered with the phagocytic potential of HKM, helped in intracellular survival of the ingested bacteria inside the HKM inducing significant HKM cytotoxicity. The immunosuppressive effect of arsenic was further evident from the ability of A. hydrophila to colonize and disseminate efficiently in exposed fish. Enzyme linked immunosorbent assay indicated that chronic exposure to arsenic suppressed the production of pro-inflammatory 'IL-1β like' factors from HKM. It is concluded that arsenic even at very low concentration is immunotoxic to fish and the changes observed in HKM may provide a useful early biomarker of low-level xenobiotic exposure

  20. Chronic exposure to low concentration of arsenic is immunotoxic to fish: Role of head kidney macrophages as biomarkers of arsenic toxicity to Clarias batrachus

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Soma; Ghosh, Debabrata [Immunobiology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India); Saha, Dhira Rani [Microscopy Laboratory, National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, C.I.T. Road, Beliaghata, Kolkata 700 010 (India); Bhattacharaya, Shelley [Environmental Toxicology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India); Mazumder, Shibnath [Immunobiology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India)], E-mail: shibnath1@yahoo.co.in

    2009-04-09

    The present study was aimed at elucidating the effect of chronic low-level arsenic exposure on the head kidney (HK) of Clarias batrachus and at determining the changes in head kidney macrophage (HKM) activity in response to arsenic exposure. Chronic exposure (30 days) to arsenic (As{sub 2}O{sub 3}, 0.50 {mu}M) led to significant increase in arsenic content in the HK accompanied by reduction in both HKM number and head kidney somatic index (HKSI). Arsenic induced HK hypertrophy, reduction in melano-macrophage population and increased hemosiderin accumulation. Transmission electron microscopy of 30 days exposed HKM revealed prominent endoplasmic reticulum, chromatin condensation and loss in structural integrity of nuclear membrane. Head kidney macrophages from exposed fish demonstrated significant levels of superoxide anions but on infection with Aeromonas hydrophila were unable to clear the intracellular bacteria and died. Exposure-challenge experiments with A. hydrophila revealed that chronic exposure to micromolar concentration of arsenic interfered with the phagocytic potential of HKM, helped in intracellular survival of the ingested bacteria inside the HKM inducing significant HKM cytotoxicity. The immunosuppressive effect of arsenic was further evident from the ability of A. hydrophila to colonize and disseminate efficiently in exposed fish. Enzyme linked immunosorbent assay indicated that chronic exposure to arsenic suppressed the production of pro-inflammatory 'IL-1{beta} like' factors from HKM. It is concluded that arsenic even at very low concentration is immunotoxic to fish and the changes observed in HKM may provide a useful early biomarker of low-level xenobiotic exposure.

  1. Assessment of arsenic exposures and controls in gallium arsenide production.

    Science.gov (United States)

    Sheehy, J W; Jones, J H

    1993-02-01

    The electronics industry is expanding the use of gallium arsenide in the production of optoelectronic devices and integrated circuits. Workers in the electronics industry using gallium arsenide are exposed to hazardous substances such as arsenic, arsine, and various acids. Arsenic requires stringent controls to minimize exposures (the current OSHA PEL for arsenic is 10 micrograms/m3 and the NIOSH REL is 2 micrograms/m3 ceiling). Inorganic arsenic is strongly implicated in respiratory tract and skin cancer. For these reasons, NIOSH researchers conducted a study of control systems for facilities using gallium arsenide. Seven walk-through surveys were performed to identify locations for detailed study which appeared to have effective controls; three facilities were chosen for in-depth evaluation. The controls were evaluated by industrial hygiene sampling. Including personal breathing zone and area air sampling for arsenic and arsine; wipe samples for arsenic also were collected. Work practices and the use of personal protective equipment were documented. This paper reports on the controls and the arsenic exposure results from the evaluation of the following gallium arsenide processes: Liquid Encapsulated Czochralski (LEC) and Horizontal Bridgeman (HB) crystal growing, LEC cleaning operations, ingot grinding/wafer sawing, and epitaxy. Results at one plant showed that in all processes except epitaxy, average arsenic exposures were at or above the OSHA action level of 5 micrograms/m3. While cleaning the LEC crystal pullers, the average potential arsenic exposure of the cleaning operators was 100 times the OSHA PEL. At the other two plants, personal exposures for arsenic were well controlled in LEC, LEC cleaning, grinding/sawing, and epitaxy operations.

  2. Cancer excess after arsenic exposure from contaminated milk powder

    DEFF Research Database (Denmark)

    Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki

    2011-01-01

    Long-term exposure to inorganic arsenic is related to increased risk of cancer in the lung, skin, bladder, and, possibly, other sites. However, little is known about the consequences of developmental exposures in regard to cancer risk. During early summer in 1955, mass arsenic poisoning of infant...... occurred in the western part of Japan because of contaminated milk powder. Okayama Prefecture was most severely affected. We examined whether the affected birth cohorts in this prefecture experienced increased cancer mortality....

  3. Protective effect of nitric oxide against arsenic-induced oxidative ...

    African Journals Online (AJOL)

    The effects of NO on alleviating arsenic-induced oxidative damage in tall fescue leaves were investigated. Arsenic (25 M) treatment induced significantly accumulation of reactive oxygen species (ROS) and led to serious lipid peroxidation in tall fescue leaves and the application of 100 M SNP before arsenic stress resulted ...

  4. Assessment of human dietary exposure to arsenic through rice.

    Science.gov (United States)

    Davis, Matthew A; Signes-Pastor, Antonio J; Argos, Maria; Slaughter, Francis; Pendergrast, Claire; Punshon, Tracy; Gossai, Anala; Ahsan, Habibul; Karagas, Margaret R

    2017-05-15

    Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. This review summarizes epidemiologic studies that examined the association between rice consumption and biomarkers of arsenic exposure. After reviewing the literature we identified 20 studies, among them included 18 observational and 2 human experimental studies that reported on associations between rice consumption and an arsenic biomarker. Among individuals not exposed to contaminated water, rice is a source of i-As exposure - rice consumption has been consistently related to arsenic biomarkers, and the relationship has been clearly demonstrated in experimental studies. Early-life i-As exposure is of particular concern due to its association with lifelong adverse health outcomes. Maternal rice consumption during pregnancy also has been associated with infant toenail total arsenic concentrations indicating that dietary exposure during pregnancy results in fetal exposure. Thus, the collective evidence indicates that rice is an independent source of arsenic exposure in populations around the world and highlights the importance of investigating its affect on health. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Protective effect of nitric oxide against arsenic-induced oxidative ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-03-15

    Mar 15, 2010 ... 1Department of Soil and Water Science, College of Resources and Environment, ... alleviated arsenic-induced electrolyte leakage and malondiadehyde (MDA) content in ..... gene construct for environmental arsenic detection.

  6. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism

    International Nuclear Information System (INIS)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark; Stachler, Elyse N.; Bibby, Kyle J.; Stolz, Donna B.; Shiva, Sruti; Wang, Zeneng; Hazen, Stanley L.; Barchowsky, Aaron; Stolz, John F.

    2015-01-01

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. - Highlights: • Arsenic exposure induces changes in host and host nitrogen metabolism that cause progresive change in the microbiome. • A polyphasic approach reveals changes

  7. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark [Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282 (United States); Stachler, Elyse N.; Bibby, Kyle J. [Department of Civil and Environmental Engineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA 15261 (United States); Stolz, Donna B. [Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 (United States); Shiva, Sruti [Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh 15261 (United States); Vascular Medicine Institute, University of Pittsburgh, Pittsburgh 15261 (United States); Wang, Zeneng; Hazen, Stanley L. [Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195 (United States); Barchowsky, Aaron, E-mail: aab20@pitt.edu [Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh 15261 (United States); Vascular Medicine Institute, University of Pittsburgh, Pittsburgh 15261 (United States); Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15219 (United States); Stolz, John F. [Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282 (United States)

    2015-12-15

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. - Highlights: • Arsenic exposure induces changes in host and host nitrogen metabolism that cause progresive change in the microbiome. • A polyphasic approach reveals changes

  8. Arsenic exposure to smelter workers. Clinical and neurophysiological studies

    Energy Technology Data Exchange (ETDEWEB)

    Blom, S.; Lagerkvist, B.; Linderholm, H.

    1985-08-01

    Forty-seven copper smelter workers, exposed to airborne arsenic for 8-40 years, were examined clinically with electromyography, and the motor and sensory conduction velocities in their arms and legs were determined. Fifty age-matched industrial workers not exposed to arsenic formed a reference group. The level of arsenic in the air at the smeltery was estimated to be below 500 micrograms/mT before 1975 and approximately 50 micrograms/mT thereafter. Urine analyses of arsenic showed a mean value of 71 micrograms/l (1 mumol/l) in the exposed group; this value is lower than that found in earlier studies reporting clinically detectable neuropathy. A slightly reduced nerve conduction velocity in two or more peripheral nerves was more common among the arsenic workers than the referents, and a statistically significant correlation between cumulative exposure to arsenic and reduced nerve conduction velocity in three peripheral motor nerves was found. This occurrence was interpreted as a sign of slight subclinical neuropathy. In conclusion the risk of clinically significant neuropathy is small when exposure is kept below 50 micrograms/mT in workroom air. The subclinical findings may be of interest in relation to the prevention of early adverse health effects from arsenic exposure.

  9. MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dwivedi, Nidhi; Mehta, Ashish; Yadav, Abhishek [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India); Binukumar, B.K.; Gill, Kiran Dip [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012 (India); Flora, Swaran J.S., E-mail: sjsflora@hotmail.com [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India)

    2011-11-15

    Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potential and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl{sub 2} ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria. -- Research highlights: Black-Right-Pointing-Pointer Arsenic impairs mitochondrial energy metabolism leading to neuronal apoptosis. Black-Right-Pointing-Pointer Arsenic differentially affects mitochondrial complexes, I - III and IV being more sensitive than complex II. Black-Right-Pointing-Pointer Arsenic-induced apoptosis initiates through ROS generation or impaired [Ca{sup 2+}]i homeostasis. Black-Right-Pointing-Pointer MiADMSA reverses arsenic toxicity via intracellular arsenic- chelation, antioxidant

  10. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Science.gov (United States)

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  11. Inorganic arsenic exposure and type 2 diabetes mellitus in Mexico

    International Nuclear Information System (INIS)

    Coronado-Gonzalez, Jose Antonio; Razo, Luz Maria del; Garcia-Vargas, Gonzalo; Sanmiguel-Salazar, Francisca; Escobedo-de la Pena, Jorge

    2007-01-01

    Inorganic arsenic exposure in drinking water has been recently related to diabetes mellitus. To evaluate this relationship the authors conducted in 2003, a case-control study in an arseniasis-endemic region from Coahuila, a northern state of Mexico with a high incidence of diabetes. The present analysis includes 200 cases and 200 controls. Cases were obtained from a previous cross-sectional study conducted in that region. Diagnosis of diabetes was established following the American Diabetes Association criteria, with two fasting glucose values ≥126 mg/100 ml (≥7.0 mmol/l) or a history of diabetes treated with insulin or oral hypoglycemic agents. The next subject studied, subsequent to the identification of a case in the cross-sectional study was taken as control. Inorganic arsenic exposure was measured through total arsenic concentrations in urine, measured by hydride-generation atomic absorption spectrophotometry. Subjects with intermediate total arsenic concentration in urine (63.5-104 μg/g creatinine) had two-fold higher risk of having diabetes (odds ratio=2.16; 95% confidence interval: 1.23, 3.79), but the risk was almost three times greater in subjects with higher concentrations of total arsenic in urine (odds ratio=2.84; 95% confidence interval: 1.64, 4.92). This data provides additional evidence that inorganic arsenic exposure may be diabetogenic

  12. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

    International Nuclear Information System (INIS)

    Herbert, Katharine J.; Holloway, Adele; Cook, Anthony L.; Chin, Suyin P.; Snow, Elizabeth T.

    2014-01-01

    Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

  13. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, Katharine J. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Holloway, Adele [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Cook, Anthony L. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Chin, Suyin P. [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Snow, Elizabeth T., E-mail: elizabeth.snow@utas.edu.au [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia)

    2014-11-15

    Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

  14. Pomegranate protects against arsenic-induced p53-dependent ROS-mediated inflammation and apoptosis in liver cells.

    Science.gov (United States)

    Choudhury, Sreetama; Ghosh, Sayan; Mukherjee, Sudeshna; Gupta, Payal; Bhattacharya, Saurav; Adhikary, Arghya; Chattopadhyay, Sreya

    2016-12-01

    Molecular mechanisms involved in arsenic-induced toxicity are complex and elusive. Liver is one of the most favored organs for arsenic toxicity as methylation of arsenic occurs mostly in the liver. In this study, we have selected a range of environmentally relevant doses of arsenic to examine the basis of arsenic toxicity and the role of pomegranate fruit extract (PFE) in combating it. Male Swiss albino mice exposed to different doses of arsenic presented marked hepatic injury as evident from histological and electron microscopic studies. Increased activities of enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase corroborated extensive liver damage. It was further noted that arsenic exposure initiated reactive oxygen species (ROS)-dependent apoptosis in the hepatocytes involving loss of mitochondrial membrane potential. Arsenic significantly increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB), coupled with increase in phosphorylated Iκ-B, possibly as adaptive cellular survival strategies. Arsenic-induced oxidative DNA damage to liver cells culminated in p53 activation and increased expression of p53 targets like miR-34a and Bax. Pomegranate polyphenols are known to possess remarkable antioxidant properties and are capable of protecting normal cells from various stimuli-induced oxidative stress and toxicities. We explored the protective role of PFE in ameliorating arsenic-induced hepatic damage. PFE was shown to reduce ROS generation in hepatocytes, thereby reducing arsenic-induced Nrf2 activation. PFE also inhibited arsenic-induced NF-κB-inflammatory pathway. Data revealed that PFE reversed arsenic-induced hepatotoxicity and apoptosis by modulating the ROS/Nrf2/p53-miR-34a axis. For the first time, we have mapped the possible signaling pathways associated with arsenic-induced hepatotoxicity and its rescue by pomegranate polyphenols. Copyright

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

    International Nuclear Information System (INIS)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy; Pillai, Ayyappan Harikrishna; Harikumar, Sankaran Kutty; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

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

  17. A Case control study of cardiovascular disease and arsenic exposure in Inner Mongolia, China

    Science.gov (United States)

    Background: Millions of people are at risk from the adverse effects of waterborne arsenic. Although the cardiovascular effects of high exposures to arsenic have been well documented, few individual level prospective studies have assessed cardiovascular risk at moderate exposures....

  18. Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study

    Science.gov (United States)

    Howard, Barbara V.; Umans, Jason G.; Gribble, Matthew O.; Best, Lyle G.; Francesconi, Kevin A.; Goessler, Walter; Lee, Elisa; Guallar, Eliseo; Navas-Acien, Ana

    2015-01-01

    OBJECTIVE Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study. RESEARCH DESIGN AND METHODS A total of 1,694 diabetes-free participants aged 45–75 years were recruited in 1989–1991 and followed through 1998–1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥126 mg/dL, 2-h glucose ≥200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications. RESULTS Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63–0.93) and 0.82 (0.73–0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations. CONCLUSIONS Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism. PMID:25583752

  19. Arsenic-induced alteration in intracellular calcium homeostasis induces head kidney macrophage apoptosis involving the activation of calpain-2 and ERK in Clarias batrachus

    International Nuclear Information System (INIS)

    Banerjee, Chaitali; Goswami, Ramansu; Datta, Soma; Rajagopal, R.; Mazumder, Shibnath

    2011-01-01

    We had earlier shown that exposure to arsenic (0.50 μM) caused caspase-3 mediated head kidney macrophage (HKM) apoptosis involving the p38-JNK pathway in Clarias batrachus. Here we examined the roles of calcium (Ca 2+ ) and extra-cellular signal-regulated protein kinase (ERK), the other member of MAPK-pathway on arsenic-induced HKM apoptosis. Arsenic-induced HKM apoptosis involved increased expression of ERK and calpain-2. Nifedipine, verapamil and EGTA pre-treatment inhibited the activation of calpain-2, ERK and reduced arsenic-induced HKM apoptosis as evidenced from reduced caspase-3 activity, Annexin V-FITC-propidium iodide and Hoechst 33342 staining. Pre-incubation with ERK inhibitor U 0126 inhibited the activation of calpain-2 and interfered with arsenic-induced HKM apoptosis. Additionally, pre-incubation with calpain-2 inhibitor also interfered with the activation of ERK and inhibited arsenic-induced HKM apoptosis. The NADPH oxidase inhibitor apocynin and diphenyleneiodonium chloride also inhibited ERK activation indicating activation of ERK in arsenic-exposed HKM also depends on signals from NADPH oxidase pathway. Our study demonstrates the critical role of Ca 2+ homeostasis on arsenic-induced HKM apoptosis. We suggest that arsenic-induced alteration in intracellular Ca 2+ levels initiates pro-apoptotic ERK and calpain-2; the two pathways influence each other positively and induce caspase-3 mediated HKM apoptosis. Besides, our study also indicates the role of ROS in the activation of ERK pathway in arsenic-induced HKM apoptosis in C. batrachus. - Highlights: → Altered Ca 2+ homeostasis leads to arsenic-induced HKM apoptosis. → Calpain-2 plays a critical role in the process. → ERK is pro-apoptotic in arsenic-induced HKM apoptosis. → Arsenic-induced HKM apoptosis involves cross talk between calpain-2 and ERK.

  20. Inhibition of insulin-dependent glucose uptake by trivalent arsenicals: possible mechanism of arsenic-induced diabetes

    International Nuclear Information System (INIS)

    Walton, Felecia S.; Harmon, Anne W.; Paul, David S.; Drobna, Zuzana; Patel, Yashomati M.; Styblo, Miroslav

    2004-01-01

    Chronic exposures to inorganic arsenic (iAs) have been associated with increased incidence of noninsulin (type-2)-dependent diabetes mellitus. Although mechanisms by which iAs induces diabetes have not been identified, the clinical symptoms of the disease indicate that iAs or its metabolites interfere with insulin-stimulated signal transduction pathway or with critical steps in glucose metabolism. We have examined effects of iAs and methylated arsenicals that contain trivalent or pentavalent arsenic on glucose uptake by 3T3-L1 adipocytes. Treatment with inorganic and methylated pentavalent arsenicals (up to 1 mM) had little or no effect on either basal or insulin-stimulated glucose uptake. In contrast, trivalent arsenicals, arsenite (iAs III ), methylarsine oxide (MAs III O), and iododimethylarsine (DMAs III O) inhibited insulin-stimulated glucose uptake in a concentration-dependent manner. Subtoxic concentrations of iAs III (20 μM), MAs III O (1 μM), or DMAs III I (2 μM) decreased insulin-stimulated glucose uptake by 35-45%. Basal glucose uptake was significantly inhibited only by cytotoxic concentrations of iAs III or MAs III O. Examination of the components of the insulin-stimulated signal transduction pathway showed that all trivalent arsenicals suppressed expression and possibly phosphorylation of protein kinase B (PKB/Akt). The concentration of an insulin-responsive glucose transporter (GLUT4) was significantly lower in the membrane region of 3T3-L1 adipocytes treated with trivalent arsenicals as compared with untreated cells. These results suggest that trivalent arsenicals inhibit insulin-stimulated glucose uptake by interfering with the PKB/Akt-dependent mobilization of GLUT4 transporters in adipocytes. This mechanism may be, in part, responsible for the development of type-2 diabetes in individuals chronically exposed to iAs

  1. High fat diet aggravates arsenic induced oxidative stress in rat heart and liver.

    Science.gov (United States)

    Dutta, Mousumi; Ghosh, Debosree; Ghosh, Arnab Kumar; Bose, Gargi; Chattopadhyay, Aindrila; Rudra, Smita; Dey, Monalisa; Bandyopadhyay, Arkita; Pattari, Sanjib K; Mallick, Sanjaya; Bandyopadhyay, Debasish

    2014-04-01

    Arsenic is a well known global groundwater contaminant. Exposure of human body to arsenic causes various hazardous effects via oxidative stress. Nutrition is an important susceptible factor which can affect arsenic toxicity by several plausible mechanisms. Development of modern civilization led to alteration in the lifestyle as well as food habits of the people both in urban and rural areas which led to increased use of junk food containing high level of fat. The present study was aimed at investigating the effect of high fat diet on heart and liver tissues of rats when they were co-treated with arsenic. This study was established by elucidating heart weight to body weight ratio as well as analysis of the various functional markers, oxidative stress biomarkers and also the activity of the antioxidant enzymes. Histological analysis confirmed the biochemical investigations. From this study it can be concluded that high fat diet increased arsenic induced oxidative stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-05

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights

  3. Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice

    International Nuclear Information System (INIS)

    Patterson, Rachel; Vega, Libia; Trouba, Kevin; Bortner, Carl; Germolec, Dori

    2004-01-01

    Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity

  4. Induction of glutathione synthesis in human hepatocytes by acute and chronic arsenic exposure: Differential roles of mitogen-activated protein kinases

    International Nuclear Information System (INIS)

    Hou, Yongyong; Wang, Yi; Wang, Huihui; Xu, Yuanyuan

    2014-01-01

    Highlights: • Arsenic exposure increased intracellular levels of glutathione. • Mitogen-activated protein kinases were involved in glutathione homeostasis. • ERK contributed to glutathione synthesis during acute arsenic exposure. • Glutathione synthesis was regulated by p38 at least in part independent of NRF2 during chronic arsenic exposure. - Abstract: Glutathione (GSH) is a vital component of antioxidant defense which protects cells from toxic insults. Previously we found intracellular GSH was involved in cell resistance against arsenic-induced cytotoxicity. However, molecular mechanisms of GSH homeostasis during arsenic exposure are largely undefined. Here, we investigated roles of mitogen-activated protein kinases (MAPKs) in GSH synthesis pathway with two arsenic exposure strategies by using Chang human hepatocytes. In one strategy, acute arsenic exposure (20 μM, 24 h) was applied, as MAPK signaling is generally considered to be transient. In the other one, chronic arsenic exposure (500 nM, 20 weeks) was applied, which mimicked the general human exposure to arsenic. We found that acute arsenic exposure activated extracellular signal-regulated 1/2 kinases (ERK1/2) and c-Jun N-terminal kinase (JNK) in parallel with increased transcription and nuclear translocation of factor-erythroid 2-related factor 2 (NRF2) and enhanced expression of γ-glutamyl cysteine ligase catalytic subunit (GCLC), resulting in elevated intracellular GSH levels. Specific ERK inhibitor abolished arsenic-induced NRF2 nuclear translocation and GSH synthesis. During chronic arsenic exposure which induced a malignant cellular phenotype, continuous p38 activation and NRF2 nuclear translocation were observed with enhanced GSH synthesis. Specific p38 inhibitor attenuated arsenic-enhanced GSH synthesis without changing NRF2 nuclear translocation. Taken together, our results indicate MAPK pathways play an important role in cellular GSH homeostasis in response to arsenic. However, the

  5. Possible mechanisms for arsenic-induced proliferative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A. [Dartmouth College and Medical School, Hanover, NH (United States)] [and others

    1996-12-31

    Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

  6. Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats.

    Science.gov (United States)

    Yadav, Rajesh S; Chandravanshi, Lalit P; Shukla, Rajendra K; Sankhwar, Madhu L; Ansari, Reyaz W; Shukla, Pradeep K; Pant, Aditya B; Khanna, Vinay K

    2011-12-01

    Our recent studies have shown that curcumin protects arsenic induced neurotoxicity by modulating oxidative stress, neurotransmitter levels and dopaminergic system in rats. As chronic exposure to arsenic has been associated with cognitive deficits in humans, the present study has been carried out to implore the neuroprotective potential of curcumin in arsenic induced cholinergic dysfunctions in rats. Rats treated with arsenic (sodium arsenite, 20mg/kg body weight, p.o., 28 days) exhibited a significant decrease in the learning activity, assessed by passive avoidance response associated with decreased binding of (3)H-QNB, known to label muscarinic-cholinergic receptors in hippocampus (54%) and frontal cortex (27%) as compared to controls. Decrease in the activity of acetylcholinesterase in hippocampus (46%) and frontal cortex (33%), staining of Nissl body, immunoreactivity of choline acetyltransferase (ChAT) and expression of ChAT protein in hippocampal region was also observed in arsenic treated rats as compared to controls. Simultaneous treatment with arsenic and curcumin (100mg/kg body weight, p.o., 28 days) increased learning and memory performance associated with increased binding of (3)H-QNB in hippocampus (54%), frontal cortex (25%) and activity of acetylcholinesterase in hippocampus (41%) and frontal cortex (29%) as compared to arsenic treated rats. Increase in the expression of ChAT protein, immunoreactivity of ChAT and staining of Nissl body in hippocampal region was also observed in rats simultaneously treated with arsenic and curcumin as compared to those treated with arsenic alone. The results of the present study suggest that curcumin significantly modulates arsenic induced cholinergic dysfunctions in brain and also exhibits neuroprotective efficacy of curcumin. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure.

    Science.gov (United States)

    Park, Robert M; Stayner, Leslie T; Petersen, Martin R; Finley-Couch, Melissa; Hornung, Richard; Rice, Carol

    2012-05-01

    Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940-2002), a revised cadmium (Cd) exposure matrix and improved work history information. Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure-response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m(3) Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20-25 years. These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 μg/m(3) Cd.

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

    International Nuclear Information System (INIS)

    Cárdenas-González, M.; Osorio-Yáñez, C.; Gaspar-Ramírez, O.; Pavković, M.; Ochoa-Martínez, A.; López-Ventura, D.

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, M. [Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA (United States); Osorio-Yáñez, C. [Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (United States); Gaspar-Ramírez, O. [Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Unidad Noreste (CIATEJ), Nuevo Leon (Mexico); Pavković, M. [Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA (United States); Renal Division, Department of Medicine, Brigham and Women' s Hospital, Boston, MA (United States); Ochoa-Martínez, A. [Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí (Mexico); López-Ventura, D. [Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), México City (Mexico); and others

    2016-10-15

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

  10. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  11. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    International Nuclear Information System (INIS)

    Zhang, Zhuo; Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok; Kim, Donghern; Shi, Xianglin

    2015-01-01

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H 2 O 2 ) and superoxide dismutase 2 (SOD2, antioxidant against O 2 ·− ) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The

  12. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

    Directory of Open Access Journals (Sweden)

    Ling-I Hsu

    2015-01-01

    Full Text Available Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1, reactive oxygen species (ROS related metabolic genes (NQO1, EPHX1, and HO-1, and DNA repair genes (XRCC1, XPD, hOGG1, and ATM together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR and 95% confidence interval (CI using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.. However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated.

  13. The die is cast: arsenic exposure in early life and disease susceptibility.

    Science.gov (United States)

    Thomas, David J

    2013-12-16

    Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for the development and progression of disease in both species. Mode of action and dosimetric studies in the mouse may help assess the role of age at exposure as a factor in susceptibility to the toxic and carcinogenic effects of arsenic in humans.

  14. Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure

    International Nuclear Information System (INIS)

    Jo, William Jaime; Ren, Xuefeng; Chu, Feixia; Aleshin, Maria; Wintz, Henri; Burlingame, Alma; Smith, Martyn Thomas; Vulpe, Chris Dillon; Zhang Luoping

    2009-01-01

    Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (As III ). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to As III through the modulation of chromatin state. We further explored the role of MYST1 and H4K16 acetylation in arsenic toxicity and carcinogenesis in human bladder epithelial cells. The expression of MYST1 was knocked down in UROtsa cells, a model of bladder epithelium that has been used to study arsenic-induced carcinogenesis. Silencing of MYST1 reduced acetylation of H4K16 and induced sensitivity to As III and to its more toxic metabolite monomethylarsonous acid (MMA III ) at doses relevant to high environmental human exposures. In addition, both As III and MMA III treatments decreased global H4K16 acetylation levels in a dose- and time-dependent manner. This indicates that acetylated H4K16 is required for resistance to arsenic and that a reduction in its levels as a consequence of arsenic exposure may contribute to toxicity in UROtsa cells. Based on these findings, we propose a novel role for the MYST1 gene in human sensitivity to arsenic.

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Assessment of Nutritional Status of Infants Living in Arsenic-Contaminated Areas in Bangladesh and Its Association with Arsenic Exposure

    Science.gov (United States)

    Milton, Abul Hasnat; Attia, John; Alauddin, Mohammad; McEvoy, Mark; McElduff, Patrick; Hussain, Sumaira; Akhter, Ayesha; Akter, Shahnaz; Islam, M. Munirul; Ahmed, AM Shamsir; Iyengar, Vasu; Islam, Md Rafiqul

    2018-01-01

    Data is scarce on early life exposure to arsenic and its association with malnutrition during infancy. This study followed the nutritional status of a cohort of 120 infants from birth to 9 months of age in an arsenic contaminated area in Bangladesh. Anthropometric data was collected at 3, 6 and 9 months of the infant’s age for nutritional assessment whereas arsenic exposure level was assessed via tube well drinking water arsenic concentration at the initiation of the study. Weight and height measurements were converted to Z-scores of weight for age (WAZ-underweight), height for age (HAZ-stunting), weight for height (WHZ-wasting) for children by comparing with WHO growth standard. Arsenic exposure levels were categorized as <50 μg/L and ≥50 μg/L. Stunting rates (<−2 SD) were 10% at 3 months and 44% at both 6 and 9 months. Wasting rates (<−2 SD) were 23.3% at 3 months and underweight rates (<−2 SD) were 25% and 10% at 3 and 6 months of age, respectively. There was a significant association of stunting with household drinking water arsenic exposure ≥50 μg/L at age of 9 months (p = 0.009). Except for stunting at 9 months of age, we did not find any significant changes in other nutritional indices over time or with levels of household arsenic exposure in this study. Our study suggests no association between household arsenic exposure and under-nutrition during infancy; with limiting factors being small sample size and short follow-up. Difference in stunting at 9 months by arsenic exposure at ≥50 μg/L might be a statistical incongruity. Further longitudinal studies are warranted to establish any association. PMID:29301293

  17. IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC-INDUCED BLADDER CANCER

    Science.gov (United States)

    Exposure to arsenic causes cancer by inducing a variety of responses that affect the expression of genes associated with numerous biological pathways leading to altered cell growth and proliferation, signaling, apoptosis and oxidative stress response. Affymetrix GeneChip® arrays ...

  18. [Studies on markers of exposure and early effect in areas with arsenic pollution: methods and results of the project SEpiAs. Epidemiological studies on population exposed to low-to-moderate arsenic concentration in drinking water].

    Science.gov (United States)

    Bustaffa, Elisa; Bianchi, Fabrizio

    2014-01-01

    Arsenic and its inorganic compounds are classified as human carcinogens. Several epidemiological studies conducted in areas of the world characterized by high arsenic concentration in drinking water, even up to 3,000 μg/l, report associations between arsenic exposure and skin, bladder, lung, liver and kidney cancer as well as cardiovascular diseases, diabetes and reproductive and developmental effects. Since general population is not exposed to these high arsenic concentrations in the last years attention focused on adverse health effects that low-to-moderate arsenic concentrations (0-150 μg/l) in drinking water could induce. The World Health Organization recommends a maximum limit of 10 μg/l for arsenic in drinking water. Almost all epidemiological studies conducted on populations exposed to low-to-moderate arsenic concentrations in drinking water are limited due to problems arising from both individual exposure assessment and low subjects number. The aim of the present review is to collect literature-based evidences regarding adverse health effects associated with exposure to low-to-moderate arsenic concentrations in drinking water (10-150 μg/l) in order to obtain a comprehensive picture of the health outcomes that such exposure can have on general population.

  19. Arsenic exposure, urinary arsenic speciation, and peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan

    International Nuclear Information System (INIS)

    Tseng, C.-H.; Huang, Y.-K.; Huang, Y.-L.; Chung, C.-J.; Yang, M.-H.; Chen, C.-J.; Hsueh, Y.-M.

    2005-01-01

    Long-term exposure to ingested inorganic arsenic is associated with peripheral vascular disease (PVD) in the blackfoot disease (BFD)-hyperendemic area in Taiwan. This study further examined the interaction between arsenic exposure and urinary arsenic speciation on the risk of PVD. A total of 479 (220 men and 259 women) adults residing in the BFD-hyperendemic area were studied. Doppler ultrasound was used to diagnose PVD. Arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE). Urinary levels of total arsenic, inorganic arsenite (As III ) and arsenate (As V ), monomethylarsonic acid (MMA V ), and dimethylarsinic acid (DMA V ) were determined. Primary methylation index [PMI = MMA V /(As III + As V )] and secondary methylation index (SMI = DMA V /MMA V ) were calculated. The association between PVD and urinary arsenic parameters was evaluated with consideration of the interaction with CAE and the confounding effects of age, sex, body mass index, total cholesterol, triglycerides, cigarette smoking, and alcohol consumption. Results showed that aging was associated with a diminishing capacity to methylate inorganic arsenic and women possessed a more efficient arsenic methylation capacity than men did. PVD risk increased with a higher CAE and a lower capacity to methylate arsenic to DMA V . The multivariate-adjusted odds ratios for CAE of 0, 0.1-15.4, and >15.4 mg/L x year were 1.00, 3.41 (0.74-15.78), and 4.62 (0.96-22.21), respectively (P 6.93, PMI > 1.77 and SMI > 6.93, PMI > 1.77 and SMI ≤ 6.93, and PMI ≤ 1.77 and SMI ≤ 6.93 were 1.00, 2.93 (0.90-9.52), 2.85 (1.05-7.73), and 3.60 (1.12-11.56), respectively (P V have a higher risk of developing PVD in the BFD-hyperendemic area in Taiwan

  20. Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap, a Hippo signaling-related protein

    International Nuclear Information System (INIS)

    Li, Changzhao; Srivastava, Ritesh K.; Elmets, Craig A.; Afaq, Farrukh; Athar, Mohammad

    2013-01-01

    Highlights: •Arsenic activates canonical Hippo signaling pathway and up-regulates αCatenin in the skin. •Arsenic activates transcriptional activity of Yap by its nuclear translocation. •Yap is involved in the disruption of tight/adherens junctions in arsenic-exposed animals. -- Abstract: Arsenic exposure in humans causes a number of toxic manifestations in the skin including cutaneous neoplasm. However, the mechanism of these alterations remains elusive. Here, we provide novel observations that arsenic induced Hippo signaling pathway in the murine skin. This pathway plays crucial roles in determining organ size during the embryonic development and if aberrantly activated in adults, contributes to the pathogenesis of epithelial neoplasm. Arsenic treatment enhanced phosphorylation-dependent activation of LATS1 kinase and other Hippo signaling regulatory proteins Sav1 and MOB1. Phospho-LATS kinase is known to catalyze the inactivation of a transcriptional co-activator, Yap. However, in arsenic-treated epidermis, we did not observed its inactivation. Thus, as expected, unphosphorylated-Yap was translocated to the nucleus in arsenic-treated epidermis. Yap by binding to the transcription factors TEADs induces transcription of its target genes. Consistently, an up-regulation of Yap-dependent target genes Cyr61, Gli2, Ankrd1 and Ctgf was observed in the skin of arsenic-treated mice. Phosphorylated Yap is important in regulating tight and adherens junctions through its binding to αCatenin. We found disruption of these junctions in the arsenic-treated mouse skin despite an increase in αCatenin. These data provide evidence that arsenic-induced canonical Hippo signaling pathway and Yap-mediated disruption of tight and adherens junctions are independently regulated. These effects together may contribute to the carcinogenic effects of arsenic in the skin

  1. The die is cast - Arsenic exposure in early life and disease susceptibility

    Science.gov (United States)

    Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

  2. Serum Acetyl Cholinesterase as a Biomarker of Arsenic Induced Neurotoxicity in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2005-04-01

    Full Text Available 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

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

    International Nuclear Information System (INIS)

    Meza, M.M.; Kopplin, M.J.; Burgess, J.L.; Gandolfi, A.J.

    2004-01-01

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

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

    Science.gov (United States)

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

    2004-10-01

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

  5. Behavioural and physical effects of arsenic exposure in fish are aggravated by aquatic algae.

    Science.gov (United States)

    Magellan, Kit; Barral-Fraga, Laura; Rovira, Marona; Srean, Pao; Urrea, Gemma; García-Berthou, Emili; Guasch, Helena

    2014-11-01

    Arsenic contamination has global impacts and freshwaters are major arsenic repositories. Arsenic toxicity depends on numerous interacting factors which makes effects difficult to estimate. The use of aquatic algae is often advocated for bioremediation of arsenic contaminated waters as they absorb arsenate and transform it into arsenite and methylated chemical species. Fish are another key constituent of aquatic ecosystems. Contamination in natural systems is often too low to cause mortality but sufficient to interfere with normal functioning. Alteration of complex, naturally occurring fish behaviours such as foraging and aggression are ecologically relevant indicators of toxicity and ideal for assessing sublethal impacts. We examined the effects of arsenic exposure in the invasive mosquitofish, Gambusia holbrooki, in a laboratory experiment incorporating some of the complexity of natural systems by including the interacting effects of aquatic algae. Our aims were to quantify the effects of arsenic on some complex behaviours and physical parameters in mosquitofish, and to assess whether the detoxifying mechanisms of algae would ameliorate any effects of arsenic exposure. Aggression increased significantly with arsenic whereas operculum movement decreased non-significantly and neither food capture efficiency nor consumption were notably affected. Bioaccumulation increased with arsenic and unexpectedly so did fish biomass. Possibly increased aggression facilitated food resource defence allowing fish to gain weight. The presence of algae aggravated the effects of arsenic exposure. For increase in fish biomass, algae acted antagonistically with arsenic, resulting in a disadvantageous reduction in weight gained. For bioaccumulation the effects were even more severe, as algae operated additively with arsenic to increase arsenic uptake and/or assimilation. Aggression was also highest in the presence of both algae and arsenic. Bioremediation of arsenic contaminated waters

  6. Blood arsenic as a biomarker of arsenic exposure: Results from a prospective study

    International Nuclear Information System (INIS)

    Hall, Marni; Chen Yu; Ahsan, Habibul; Slavkovich, Vesna; Geen, Alexander van; Parvez, Faruque; Graziano, Joseph

    2006-01-01

    Exposure to arsenic (As)-contaminated drinking water affects millions of people worldwide. Arsenic exposure is associated with skin lesions, skin, lung, kidney and liver cancers, neurologic and cardiovascular effects. Past studies involving biomarkers of As exposure have typically examined urinary As (UAs) (adjusted for urinary creatinine), hair or toenail As, but not blood As (BAs) since blood concentrations are exceedingly low and are not detectable by conventional atomic absorption spectrophotometric techniques. In a case-cohort analysis of 303 newly diagnosed cases of skin lesions, and 849 subcohort members randomly selected from 8092 participants in the health effects of as longitudinal study (HEALS) in Araihazar, Bangladesh, we measured blood, urine and water As concentrations, and examined their associations with each other, and with the risk for skin lesions. BAs concentrations were highly correlated with creatinine-adjusted UAs concentrations (r = 0.85) and with water As (WAs) (r = 0.75). We observed consistent dose-response relationships between the risk of skin lesions and all the measures of As exposure. Rate ratios (RRs) for skin lesions by quintile of As exposure, adjusted for age and gender, revealed that the two highest quintiles were significantly related to an increased risk of skin lesions for each measure of exposure: BAs, UAs, WAs and a time-weighted water As variable. This prospective study confirms the increased risk of skin lesions in relation to As concentrations in blood, urine and water and also establishes that BAs is a useful biomarker of As exposure in this study population

  7. Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lei; Hitron, John Andrew [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Wise, James T.F. [Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Son, Young-Ok; Roy, Ram Vinod [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern; Dai, Jin [Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Zhang, Zhuo [Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Xu, Mei; Luo, Jia [Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin, E-mail: xshi5@uky.edu [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

    2015-10-15

    Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development. - Highlights: • Arsenic is able to induce Cox-2 expression in colorectal cancer cells. • Ethanol, a diet nutritional factor, could enhance arsenic-induced Cox-2. • The up-regulation of Cox-2 via both NFAT and NF-κB activities.

  8. Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells

    International Nuclear Information System (INIS)

    Wang, Lei; Hitron, John Andrew; Wise, James T.F.; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Xu, Mei; Luo, Jia; Shi, Xianglin

    2015-01-01

    Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development. - Highlights: • Arsenic is able to induce Cox-2 expression in colorectal cancer cells. • Ethanol, a diet nutritional factor, could enhance arsenic-induced Cox-2. • The up-regulation of Cox-2 via both NFAT and NF-κB activities.

  9. Site-specific data confirm arsenic exposure predicted by the U.S. Environmental Protection Agency.

    Science.gov (United States)

    Walker, S; Griffin, S

    1998-03-01

    The EPA uses an exposure assessment model to estimate daily intake to chemicals of potential concern. At the Anaconda Superfund site in Montana, the EPA exposure assessment model was used to predict total and speciated urinary arsenic concentrations. Predicted concentrations were then compared to concentrations measured in children living near the site. When site-specific information on concentrations of arsenic in soil, interior dust, and diet, site-specific ingestion rates, and arsenic absorption rates were used, measured and predicted urinary arsenic concentrations were in reasonable agreement. The central tendency exposure assessment model successfully described the measured urinary arsenic concentration for the majority of children at the site. The reasonable maximum exposure assessment model successfully identified the uppermost exposed population. While the agreement between measured and predicted urinary arsenic is good, it is not exact. The variables that were identified which influenced agreement included soil and dust sample collection methodology, daily urinary volume, soil ingestion rate, and the ability to define the exposure unit. The concentration of arsenic in food affected agreement between measured and predicted total urinary arsenic, but was not considered when comparing measured and predicted speciated urinary arsenic. Speciated urinary arsenic is the recommended biomarker for recent inorganic arsenic exposure. By using site-specific data in the exposure assessment model, predicted risks from exposure to arsenic were less than predicted risks would have been if the EPA's default values had been used in the exposure assessment model. This difference resulted in reduced magnitude and cost of remediation while still protecting human health.

  10. Arsenic: bioaccessibility from seaweed and rice, dietary exposure calculations and risk assessment.

    Science.gov (United States)

    Brandon, Esther F A; Janssen, Paul J C M; de Wit-Bos, Lianne

    2014-01-01

    Arsenic is a metalloid that occurs in food and the environment in different chemical forms. Inorganic arsenic is classified as a class I carcinogen. The inorganic arsenic intake from food and drinking water varies depending on the geographic arsenic background. Non-dietary exposure to arsenic is likely to be of minor importance for the general population within the European Union. In Europe, arsenic in drinking water is on average low, but food products (e.g. rice and seaweed) are imported from all over the world including from regions with naturally high arsenic levels. Therefore, specific populations living in Europe could also have a high exposure to inorganic arsenic due to their consumption pattern. Current risk assessment is based on exposure via drinking water. For a good estimation of the risks of arsenic in food, it is important to investigate if the bioavailability of inorganic arsenic from food is different from drinking water. The present study further explores the issue of European dietary exposure to inorganic arsenic via rice and seaweed and its associated health risks. The bioavailability of inorganic arsenic was measured in in vitro digestion experiments. The data indicate that the bioavailability of inorganic arsenic is similar for rice and seaweed compared with drinking water. The calculated dietary intake for specific European Union populations varied between 0.44 and 4.51 µg kg⁻¹ bw day⁻¹. The margins of exposure between the inorganic intake levels and the BMDL0.5 values as derived by JECFA are low. Decreasing the intake of inorganic arsenic via Hijiki seaweed could be achieved by setting legal limits similar to those set for rice by the Codex Alimentarius Commission in July 2014.

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

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, L.R.; Farmer, J.G. (Memphis State Univ., TN (United States) Univ. of Edinburgh (United Kingdom))

    1991-01-01

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

  12. Site-specific data confirm arsenic exposure predicted by the U.S. Environmental Protection Agency.

    OpenAIRE

    Walker, S; Griffin, S

    1998-01-01

    The EPA uses an exposure assessment model to estimate daily intake to chemicals of potential concern. At the Anaconda Superfund site in Montana, the EPA exposure assessment model was used to predict total and speciated urinary arsenic concentrations. Predicted concentrations were then compared to concentrations measured in children living near the site. When site-specific information on concentrations of arsenic in soil, interior dust, and diet, site-specific ingestion rates, and arsenic abso...

  13. Molecular basis for arsenic-Induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction

    International Nuclear Information System (INIS)

    Kumagai, Yoshito; Pi Jingbo

    2004-01-01

    Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed

  14. Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

    Energy Technology Data Exchange (ETDEWEB)

    Ngalame, Ntube N.O., E-mail: ngalamenn@niehs.nih.gov; Makia, Ngome L., E-mail: makianl@niehs.nih.gov; Waalkes, Michael P., E-mail: waalkes@niehs.nih.gov; Tokar, Erik J., E-mail: tokare@mail.nih.gov

    2016-12-01

    Inorganic arsenic, an environmental contaminant and a human carcinogen is associated with prostate cancer. Emerging evidence suggests that cancer stem cells (CSCs) are the driving force of carcinogenesis. Chronic arsenic exposure malignantly transforms the human normal prostate stem/progenitor cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs), through unknown mechanisms. MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. In prior work, miR-143 was markedly downregulated in As-CSCs, suggesting a role in arsenic-induced malignant transformation. In the present study, we investigated whether loss of miR-143 expression is important in arsenic-induced transformation of prostate SCs. Restoration of miR-143 in As-CSCs was achieved by lentivirus-mediated miR-143 overexpression. Cells were assessed bi-weekly for up to 30 weeks to examine mitigation of cancer phenotype. Secreted matrix metalloproteinase (MMP) activity was increased by arsenic-induced malignant transformation, but miR-143 restoration decreased secreted MMP-2 and MMP-9 enzyme activities compared with scramble controls. Increased cell proliferation and apoptotic resistance, two hallmarks of cancer, were decreased upon miR-143 restoration. Increased apoptosis was associated with decreased BCL2 and BCL-XL expression. miR-143 restoration dysregulated the expression of SC/CSC self-renewal genes including NOTCH-1, BMI-1, OCT4 and ABCG2. The anticancer effects of miR-143 overexpression appeared to be mediated by targeting and inhibiting LIMK1 protein, and the phosphorylation of cofilin, a LIMK1 substrate. These findings clearly show that miR-143 restoration mitigated multiple cancer characteristics in the As-CSCs, suggesting a potential role in arsenic-induced transformation of prostate SCs. Thus, miR-143 is a potential biomarker and therapeutic target for arsenic-induced prostate cancer. - Highlights: • Chronic arsenic exposure

  15. Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

    International Nuclear Information System (INIS)

    Ngalame, Ntube N.O.; Makia, Ngome L.; Waalkes, Michael P.; Tokar, Erik J.

    2016-01-01

    Inorganic arsenic, an environmental contaminant and a human carcinogen is associated with prostate cancer. Emerging evidence suggests that cancer stem cells (CSCs) are the driving force of carcinogenesis. Chronic arsenic exposure malignantly transforms the human normal prostate stem/progenitor cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs), through unknown mechanisms. MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. In prior work, miR-143 was markedly downregulated in As-CSCs, suggesting a role in arsenic-induced malignant transformation. In the present study, we investigated whether loss of miR-143 expression is important in arsenic-induced transformation of prostate SCs. Restoration of miR-143 in As-CSCs was achieved by lentivirus-mediated miR-143 overexpression. Cells were assessed bi-weekly for up to 30 weeks to examine mitigation of cancer phenotype. Secreted matrix metalloproteinase (MMP) activity was increased by arsenic-induced malignant transformation, but miR-143 restoration decreased secreted MMP-2 and MMP-9 enzyme activities compared with scramble controls. Increased cell proliferation and apoptotic resistance, two hallmarks of cancer, were decreased upon miR-143 restoration. Increased apoptosis was associated with decreased BCL2 and BCL-XL expression. miR-143 restoration dysregulated the expression of SC/CSC self-renewal genes including NOTCH-1, BMI-1, OCT4 and ABCG2. The anticancer effects of miR-143 overexpression appeared to be mediated by targeting and inhibiting LIMK1 protein, and the phosphorylation of cofilin, a LIMK1 substrate. These findings clearly show that miR-143 restoration mitigated multiple cancer characteristics in the As-CSCs, suggesting a potential role in arsenic-induced transformation of prostate SCs. Thus, miR-143 is a potential biomarker and therapeutic target for arsenic-induced prostate cancer. - Highlights: • Chronic arsenic exposure

  16. Arsenic may be involved in fluoride-induced bone toxicity through PTH/PKA/AP1 signaling pathway.

    Science.gov (United States)

    Zeng, Qi-bing; Xu, Yu-yan; Yu, Xian; Yang, Jun; Hong, Feng; Zhang, Ai-hua

    2014-01-01

    Chronic exposure to combined fluoride and arsenic continues to be a major public health problem worldwide, affecting thousands of people. In recent years, more and more researchers began to focus on the interaction between the fluorine and the arsenic. In this study, the selected investigation site was located in China. The study group was selected from people living in fluoride-arsenic polluted areas due to burning coal. The total number of participants was 196; including the fluoride-arsenic anomaly group (130) and the fluoride-arsenic normal group (63). By observing the changes in gene and protein expression of PTH/PKA/AP1 signaling pathway, the results show that fluoride can increase the expression levels of PTH, PKA, and AP1, but arsenic can only affect the expression of AP1; fluoride and arsenic have an interaction on the expression of AP1. Further study found that fluoride and arsenic can affect the mRNA expression level of c-fos gene (AP1 family members), and have an interaction on the expression of c-fos, but not c-jun. The results indicate that PTH/PKA/AP1 signaling pathway may play an important role in bone toxicity of fluoride. Arsenic can affect the expression of c-fos, thereby affecting the expression of transcription factor AP1, indirectly involved in fluoride-induced bone toxicity. Copyright © 2013. Published by Elsevier B.V.

  17. Study on the toxic effects induced by different arsenicals in primary cultured rat astroglia

    International Nuclear Information System (INIS)

    Jin Yaping; Sun Guifan; Li Xin; Li Gexin; Lu Chunwei; Qu Long

    2004-01-01

    Arsenic toxicity is a global health problem affecting millions of people. The objectives of this study were to determine if the toxic effects on primary cultured rat astroglia would be induced by different arsenicals. Based on alamarBlue assay and the single cell gel electrophoresis (SCGE, comet assay), the cell viability and DNA damage in the cells exposed to different arsenicals were evaluated. Treatment of astroglia with methylated arsenicals, that is, pentavalent monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV), resulted in no obvious changes in cell viability and DNA damage at micromolar concentrations. However, treatment of astroglia with inorganic arsenicals, that is, arsenite and arsenate, caused decreased cell viability and increased DNA damage at micromolar levels, and showing a dose-related decrease in mean alamarBlue reduced rate and a dose-related increase in mean comet length. Our study is therefore highly suggestive for a link between inorganic exposure and cellular toxicity or DNA damage. Based on the results of this study, the toxic effects induced by arsenite were stronger than those induced by arsenate

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

    Science.gov (United States)

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

    2017-11-01

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  20. Cardiovascular disease and arsenic exposure in Inner Mongolia, China: a case control study

    Science.gov (United States)

    BACKGROUND: Millions of people are at risk from the adverse effects of arsenic exposure through drinking water. Increasingly, non-cancer effects such as cardiovascular disease have been associated with drinking water arsenic exposures. However, most studies have been conducted in...

  1. High soil and groundwater arsenic levels induce high body arsenic loads, health risk and potential anemia for inhabitants of northeastern Iran.

    Science.gov (United States)

    Taheri, Masumeh; Mehrzad, Jalil; Mahmudy Gharaie, Mohamad Hosein; Afshari, Reza; Dadsetan, Ahmad; Hami, Shakiba

    2016-04-01

    Arsenic bioavailability in rock, soil and water resources is notoriously hazardous. Geogenic arsenic enters the body and adversely affects many biochemical processes in animals and humans, posing risk to public health. Chelpu is located in NE Iran, where realgar, orpiment and pyrite mineralization is the source of arsenic in the macroenvironment. Using cluster random sampling strategy eight rocks, 23 soils, 12 drinking water resources, 36 human urine and hair samples and 15 adult sheep urine and wool samples in several large-scale herds in the area were randomly taken for quantification of arsenic in rock/soil/water, wool/hair/urine. Arsenic levels in rock/soil/water and wool/hair/urine were measured using inductively coupled plasma spectroscopy and atomic absorption spectrophotometry, respectively. While arsenic levels in rocks, soils and water resources hazardously ranged 9.40-25,873.3 mg kg(-1), 7.10-1448.80 mg kg(-1) and 12-606 μg L(-1), respectively, arsenic concentrations in humans' hair and urine and sheep's wool and urine varied from 0.37-1.37 μg g(-1) and 9-271.4 μg L(-1) and 0.3-3.11 μg g(-1) and 29.1-1015 μg L(-1), respectively. Local sheep and human were widely sick and slightly anemic. Hematological examination of the inhabitants revealed that geogenic arsenic could harm blood cells, potentially resulting in many other hematoimmunological disorders including cancer. The findings warn widespread exposure of animals and human in this agroecologically and geopolitically important region (i.e., its proximity with Afghanistan, Pakistan and Turkmenistan) and give a clue on how arsenic could induce infectious and non-infectious diseases in highly exposed human/animals.

  2. Toxicological effects of arsenic exposure in a freshwater teleost fish ...

    African Journals Online (AJOL)

    High concentration of arsenic in groundwater in the north-eastern states of India has become a major cause of concern. Inorganic arsenic of geological origin is found in groundwater used as drinking-water in several parts of the world. Arsenic is used in various industries and agriculture and excessive arsenic finds its way ...

  3. α-Lipoic Acid Mitigates Arsenic-Induced Hematological Abnormalities in Adult Male Rats

    Directory of Open Access Journals (Sweden)

    Sonali Ghosh

    2017-05-01

    Full Text Available Background: Arsenic toxicity is a major global health problem and exposure via contaminated drinking water has been associated with hematological and other systemic disorders. The present investigation has been conducted in adult male rats to evaluate the protective ability of α-lipoic acid (ALA against such hematological disorders. Methods: Twenty-four adult male Wister rats (b.wt.130±10g were grouped and accordingly group I (control received the normal diet, group II (treated was given arsenic orally for 28 consecutive days as arsenic trioxide (3 mg/kgbw/rat/day whereas group III (supplemented received the same dose of arsenic along with ALA (25 mg/kgbw/rat/day as oral supplement. Hematological profile, plasma oxidant/antioxidant status, and erythrocyte morphology were assessed. Statistical analysis was done by one-way ANOVA using SPSS software (version 16.0. Results: Arsenic exposure caused reduction of erythrocyte (P=0.021, leucocyte (P<0.001, and hemoglobin (P=0.031 associated with echinocytic transformation as evidenced by light and scanning electron microscopic studies. The other significantly altered parameters include increased mean corpuscular volume (P=0.041 and lymphocytopenia (P<0.001 with insignificant neutropenia and eosinophilia. Altered serum oxidative balance as evidenced by decreased TAS (P<0.001 and increased TOS (P<0.001 with OSI (P<0.001 was also noted. The dietary supplementation of ALA has a beneficial effect against the observed (P<0.05 arsenic toxicities. It brings about the protection by restoring the hematological redox and inflammatory status near normal in treated rats. Arsenic-induced morphological alteration of erythrocytes was also partially attenuated by ALA supplementation. Conclusion: It is concluded that arsenicosis is associated with hematological alterations and ALA co-supplementation can partially alleviate these changes in an experimental male rat model.

  4. Association between arsenic exposure and plasma cholinesterase activity: a population based study in Bangladesh

    Directory of Open Access Journals (Sweden)

    Karim Md Rezaul

    2010-07-01

    Full Text Available Abstract Background Arsenic is a potent pollutant that has caused an environmental catastrophe in certain parts of the world including Bangladesh where millions of people are presently at risk due to drinking water contaminated by arsenic. Chronic arsenic exposure has been scientifically shown as a cause for liver damage, cancers, neurological disorders and several other ailments. The relationship between plasma cholinesterase (PChE activity and arsenic exposure has not yet been clearly documented. However, decreased PChE activity has been found in patients suffering liver dysfunction, heart attack, cancer metastasis and neurotoxicity. Therefore, in this study, we evaluated the PChE activity in individuals exposed to arsenic via drinking water in Bangladesh. Methods A total of 141 Bangladeshi residents living in arsenic endemic areas with the mean arsenic exposure of 14.10 ± 3.27 years were selected as study subjects and split into tertile groups based on three water arsenic concentrations: low ( 265 μg/L. Study subjects were further sub-divided into two groups (≤50 μg/L and > 50 μg/L based on the recommended upper limit of water arsenic concentration (50 μg/L in Bangladesh. Blood samples were collected from the study subjects by venipuncture and arsenic concentrations in drinking water, hair and nail samples were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS. PChE activity was assayed by spectrophotometer. Results Arsenic concentrations in hair and nails were positively correlated with the arsenic levels in drinking water. Significant decreases in PChE activity were observed with increasing concentrations of arsenic in water, hair and nails. The average levels of PChE activity in low, medium and high arsenic exposure groups were also significantly different between each group. Lower levels of PChE activity were also observed in the > 50 μg/L group compared to the ≤50 μg/L group. Moreover, PChE activity was

  5. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    International Nuclear Information System (INIS)

    Tan, Min; Schmidt, Robin H.; Beier, Juliane I.; Watson, Walter H.; Zhong, Hai; States, J. Christopher; Arteel, Gavin E.

    2011-01-01

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a ‘2-hit’ paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet (± arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: ► Characterizes a mouse model of arsenic enhanced NAFLD. ► Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. ► This effect is associated with increased inflammation.

  6. Postnatal arsenic exposure and attention impairment in school children.

    Science.gov (United States)

    Rodríguez-Barranco, Miguel; Gil, Fernando; Hernández, Antonio F; Alguacil, Juan; Lorca, Andres; Mendoza, Ramón; Gómez, Inmaculada; Molina-Villalba, Isabel; González-Alzaga, Beatriz; Aguilar-Garduño, Clemente; Rohlman, Diane S; Lacasaña, Marina

    2016-01-01

    Over the last few decades there has been an increased concern about the health risks from exposure to metallic trace elements, including arsenic, because of their potential neurotoxic effects on the developing brain. This study assessed whether urinary arsenic (UA) levels are associated with attention performance and Attention-Deficit/Hyperactivity Disorder (ADHD) in children living in an area with high industrial and mining activities in Southwestern Spain. A cross-sectional study was conducted on 261 children aged 6-9 years. Arsenic levels were determined in urine samples. Attention was measured by using 4 independent tools: a) tests from the Behavioral Assessment and Research System (BARS) designed to measure attention function: Simple Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT); b) AULA Test, a virtual reality (VR)-based test that evaluates children's response to several stimuli in an environment simulating a classroom; c) Child Behavior Checklist (CBCL), administered to parents; and d) Teacher's Report Form (TRF), administered to teachers. Multivariate linear and logistic regression models, adjusted for potential confounders, were used to estimate the magnitude of the association between UA levels and attention performance scores. Higher UA levels were associated with an increased latency of response in RTT (β = 12.3; 95% confidence interval (CI): 3.5-21.1) and SAT (β = 3.6; 95% CI: .4-6.8) as well as with worse performance on selective and focalized attention in the AULA test (β for impulsivity = .6; 95% CI: .1-1.1; β for inattention = .5; 95% CI: .03-1.0). A dose-response relationship was observed between UA levels and inattention and impulsivity scores. In contrast, results from the CBCL and TRF tests failed to show a significant association with UA levels. In conclusion, UA levels were associated with impaired attention/cognitive function, even at levels considered safe. These results provide

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

  9. Distribution and speciation of arsenic by transplacental and early life exposure to inorganic arsenic in offspring rats.

    Science.gov (United States)

    Xi, Shuhua; Jin, Yaping; Lv, Xiuqiang; Sun, Guifan

    2010-04-01

    The amount of arsenic compounds was determined in the liver and brain of pups and in breast milk in the pup's stomach in relation to the route of exposure: transplacental, breast milk, or drinking water. Forty-eight pregnant rats were randomly divided into four groups, each group was given free access to drinking water that contained 0, 10, 50, and 100 mg/L NaAsO(2) from gestation day 6 (GD 6) until postnatal day 42 (PND 42). Once pups were weaned, they started to drink the same arsenic-containing water as the dams. Contents of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsenic acid (TMA) in livers and brains of the pups on PND 0, 15, 28, and 42 and breast milk taken from the pup's stomach on PND 0 and 15 were detected using the hydride generation atomic absorption spectroscopy method. Concentrations of iAs, MMA, and DMA in the breast milk, the brain, and the liver of the pups increased with the concentration of arsenic in drinking water on PND 0, 15, 28, and 42. Compared to the liver or brain, breast milk had the lowest arsenic concentrations. There was a significant decrease in the levels of arsenic species on PND 15 compared to PND 0, 28, or 42. It was confirmed that arsenic species can pass through the placental barrier from dams to offspring and across the blood-brain barrier in the pups, and breast milk from dams exposed to arsenic in drinking water contains less arsenic than the liver and brain of pups.

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

    Science.gov (United States)

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

  11. Human health risks and socio-economic perspectives of arsenic exposure in Bangladesh: A scoping review.

    Science.gov (United States)

    Rahman, M Azizur; Rahman, A; Khan, M Zaved Kaiser; Renzaho, Andre M N

    2018-04-15

    Arsenic contamination of drinking water, which can occur naturally or because of human activities such as mining, is the single most important public health issue in Bangladesh. Fifty out of the 64 districts in the country have arsenic concentration of groundwater exceeding 50µgL -1 , the Bangladeshi threshold, affecting 35-77 million people or 21-48% of the total population. Chronic arsenic exposure through drinking water and other dietary sources is an important public health issue worldwide affecting hundreds of millions of people. Consequently, arsenic poisoning has attracted the attention of researchers and has been profiled extensively in the literature. Most of the literature has focused on characterising arsenic poisoning and factors associated with it. However, studies examining the socio-economic aspects of chronic exposure of arsenic through either drinking water or foods remain underexplored. The objectives of this paper are (i) to review arsenic exposure pathways to humans; (ii) to summarise public health impacts of chronic arsenic exposure; and (iii) to examine socio-economic implications and consequences of arsenicosis with a focus on Bangladesh. This scoping review evaluates the contributions of different exposure pathways by analysing arsenic concentrations in dietary and non-dietary sources. The socio-economic consequences of arsenicosis disease in Bangladesh are discussed in this review by considering food habits, nutritional status, socio-economic conditions, and socio-cultural behaviours of the people of the country. The pathways of arsenic exposure in Bangladesh include drinking water, various plant foods and non-dietary sources such as soil. Arsenic affected people are often abandoned by the society, lose their jobs and get divorced and are forced to live a sub-standard life. The fragile public health system in Bangladesh has been burdened by the management of thousands of arsenicosis victims in Bangladesh. Copyright © 2017 Elsevier Inc

  12. Characterizing arsenic in preserved hair for assessing exposure potential and discriminating poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Kempson, Ivan M.; Henry, Dermot; Francis, James; (Museum Vic.); (U. South Australia); (UWO)

    2009-05-21

    Advanced analytical techniques have been used to characterize arsenic in taxidermy specimens. Arsenic was examined to aid in discriminating its use as a preservative from that incorporated by ingestion and hence indicate poisoning (in the case of historical figures). The results are relevant to museum curators, occupational and environmental exposure concerns, toxicological and anthropological investigations. Hair samples were obtained from six taxidermy specimens preserved with arsenic in the late 1800s and early 1900s to investigate the arsenic incorporation. The presence of arsenic poses a potential hazard in museum and private collections. For one sample, arsenic was confirmed to be present on the hair with time-of-flight secondary ion mass spectrometry and then measured with neutron activation analysis to comprise 176 {mu}g g{sup -1}. The hair cross section was analysed with synchrotron micro-X-ray fluorescence to investigate the transverse distribution of topically applied arsenic. It was found that the arsenic had significantly penetrated all hair samples. Association with melanin clusters and the medulla was observed. Lead and mercury were also identified in one sample. X-ray absorption near-edge spectroscopy of the As K-edge indicated that an arsenate species predominantly existed in all samples; however, analysis was hindered by very rapid photoreduction of the arsenic. It would be difficult to discriminate arsenic consumption from topically applied arsenic based on the physical transverse distribution. Longitudinal distributions and chemical speciation may still allow differentiation.

  13. Association between occupational exposure to arsenic and neurological, respiratory and renal effects

    International Nuclear Information System (INIS)

    Halatek, Tadeusz; Sinczuk-Walczak, Halina; Rabieh, Sasan; Wasowicz, Wojciech

    2009-01-01

    Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n = 16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and β 2 -microglobulin (β 2 M) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m 3 ). The contents of lead did not exceed the TLV (0.05 mg/m 3 ). Low CC16 levels in serum (12.1 μg/l) of workers with SNS and VEP symptoms and highest level As-U (x a 39.0 μg/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum β 2 M and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system.

  14. The Association of Arsenic Exposure and Arsenic Metabolism with the Metabolic Syndrome and its Individual Components: Prospective Evidence from the Strong Heart Family Study.

    Science.gov (United States)

    Spratlen, Miranda J; Grau-Perez, Maria; Best, Lyle G; Yracheta, Joseph; Lazo, Mariana; Vaidya, Dhananjay; Balakrishnan, Poojitha; Gamble, Mary V; Francesconi, Kevin A; Goessler, Walter; Cole, Shelley A; Umans, Jason G; Howard, Barbara V; Navas-Acien, Ana

    2018-03-15

    Inorganic arsenic exposure is ubiquitous and both exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. The association between arsenic exposure and arsenic metabolism with metabolic syndrome and its individual components, however, is relatively unknown. We used poisson regression with robust variance to evaluate the association between baseline arsenic exposure (urine arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident metabolic syndrome and its individual components (elevated waist circumference, elevated triglycerides, reduced HDL, hypertension, elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort in American Indian communities (baseline visits in 1998-1999 and 2001-2003, follow-up visits in 2001-2003 and 2006-2009). 32% of participants developed metabolic syndrome over follow-up. An IQR increase in arsenic exposure was associated with 1.19 (95% CI: 1.01, 1.41) greater risk for elevated fasting plasma glucose but not with other individual components or overall metabolic syndrome. Arsenic metabolism, specifically lower MMA% and higher DMA% was associated with higher risk of overall metabolic syndrome and elevated waist circumference, but not with any other component. These findings support there is a contrasting and independent association between arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.

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

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chao-Yuan [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Chu, Jan-Show [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Yang, Hsiu-Yuan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical Universtiy-Shuang Ho Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China)

    2012-08-01

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

  16. Redox proteomics changes in the fungal pathogen Trichosporon asahii on arsenic exposure: identification of protein responses to metal-induced oxidative stress in an environmentally-sampled isolate.

    Directory of Open Access Journals (Sweden)

    Sidra Ilyas

    Full Text Available Trichosporon asahii is a yeast pathogen implicated in opportunistic infections. Cultures of an isolate collected from industrial wastewater were exposed for 2 days to 100 mg/L sodium arsenite (NaAsO2 and cadmium (CdCl2. Both metals reduced glutathione transferase (GST activity but had no effect on superoxide dismutase or catalase. NaAsO2 exposure increased glutathione reductase activity while CdCl2 had no effect. Protein thiols were labeled with 5-iodoacetamido fluorescein followed by one dimensional electrophoresis which revealed extensive protein thiol oxidation in response to CdCl2 treatment but thiol reduction in response to NaAsO2. Two dimensional electrophoresis analyses showed that the intensity of some protein spots was enhanced on treatment as judged by SameSpots image analysis software. In addition, some spots showed decreased IAF fluorescence suggesting thiol oxidation. Selected spots were excised and tryptic digested for identification by MALDI-TOF/TOF MS. Twenty unique T. asahii proteins were identified of which the following proteins were up-regulated in response to NaAsO2: 3-isopropylmalate dehydrogenase, phospholipase B, alanine-glyoxylate aminotransferase, ATP synthase alpha chain, 20S proteasome beta-type subunit Pre3p and the hypothetical proteins A1Q1_08001, A1Q2_03020, A1Q1_06950, A1Q1_06913. In addition, the following showed decreased thiol-associated fluorescence consistent with thiol oxidation; aconitase; aldehyde reductase I; phosphoglycerate kinase; translation elongation factor 2; heat shock protein 70 and hypothetical protein A1Q2_04745. Some proteins showed both increase in abundance coupled with decrease in IAF fluorescence; 3-hydroxyisobutyryl-CoA hydrolase; homoserine dehydrogenase Hom6 and hypothetical proteins A1Q2_03020 and A1Q1_00754. Targets implicated in redox response included 10 unique metabolic enzymes, heat shock proteins, a component of the 20S proteasome and translation elongation factor 2. These data

  17. Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.

    Science.gov (United States)

    Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin

    2016-11-01

    Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd

  18. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    International Nuclear Information System (INIS)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91 st day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E max of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  19. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

    2014-10-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Gordon, E-mail: gordon.gong@ttuhsc.edu [F. Marie Hall Institute for Rural and Community Health, Texas Tech University Health Sciences Center, Lubbock, TX (United States); Basom, Janet [F. Marie Hall Institute for Rural and Community Health, Texas Tech University Health Sciences Center, Lubbock, TX (United States); Department of Family and Community Medicine, Texas Tech University Health Sciences Center, Lubbock, TX (United States); Mattevada, Sravan [Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX (United States); Onger, Frederick [Department of Family and Community Medicine, Texas Tech University Health Sciences Center, Lubbock, TX (United States)

    2015-04-15

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

  2. Arsenic transformation predisposes human skin keratinocytes to UV-induced DNA damage yet enhances their survival apparently by diminishing oxidant response

    International Nuclear Information System (INIS)

    Sun Yang; Kojima, Chikara; Chignell, Colin; Mason, Ronald; Waalkes, Michael P.

    2011-01-01

    Inorganic arsenic and UV, both human skin carcinogens, may act together as skin co-carcinogens. We find human skin keratinocytes (HaCaT cells) are malignantly transformed by low-level arsenite (100 nM, 30 weeks; termed As-TM cells) and with transformation concurrently undergo full adaptation to arsenic toxicity involving reduced apoptosis and oxidative stress response to high arsenite concentrations. Oxidative DNA damage (ODD) is a possible mechanism in arsenic carcinogenesis and a hallmark of UV-induced skin cancer. In the current work, inorganic arsenite exposure (100 nM) did not induce ODD during the 30 weeks required for malignant transformation. Although acute UV-treatment (UVA, 25 J/cm 2 ) increased ODD in passage-matched control cells, once transformed by arsenic to As-TM cells, acute UV actually further increased ODD (> 50%). Despite enhanced ODD, As-TM cells were resistant to UV-induced apoptosis. The response of apoptotic factors and oxidative stress genes was strongly mitigated in As-TM cells after UV exposure including increased Bcl2/Bax ratio and reduced Caspase-3, Nrf2, and Keap1 expression. Several Nrf2-related genes (HO-1, GCLs, SOD) showed diminished responses in As-TM cells after UV exposure consistent with reduced oxidant stress response. UV-exposed As-TM cells showed increased expression of cyclin D1 (proliferation gene) and decreased p16 (tumor suppressor). UV exposure enhanced the malignant phenotype of As-TM cells. Thus, the co-carcinogenicity between UV and arsenic in skin cancer might involve adaptation to chronic arsenic exposure generally mitigating the oxidative stress response, allowing apoptotic by-pass after UV and enhanced cell survival even in the face of increased UV-induced oxidative stress and increased ODD. - Highlights: → Arsenic transformation adapted to UV-induced apoptosis. → Arsenic transformation diminished oxidant response. → Arsenic transformation enhanced UV-induced DNA damage.

  3. Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2013-01-01

    Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal lif...

  4. Reduced cellular DNA repair capacity after environmentally relevant arsenic exposure. Influence of Ogg1 deficiency

    International Nuclear Information System (INIS)

    Bach, Jordi; Peremartí, Jana; Annangi, Balasubramnayam; Marcos, Ricard; Hernández, Alba

    2015-01-01

    Highlights: • Repair ability under long-term exposure to arsenic was tested using the comet assay. • Effects were measured under Ogg1 wild-type and deficient backgrounds. • Exposed cells repair less efficiency the DNA damage induced by SA, KBrO 3 , MMA III or UVC radiation. • Oxidative damage and Ogg1 deficient background exacerbate repair deficiencies. • Overexpression of the arsenic metabolizing enzyme As3mt acts as adaptive mechanism. - Abstract: Inorganic arsenic (i-As) is a genotoxic and carcinogenic environmental contaminant known to affect millions of people worldwide. Our previous work demonstrated that chronic sub-toxic i-As concentrations were able to induce biologically significant levels of genotoxic and oxidative DNA damage that were strongly influenced by the Ogg1 genotype. In order to study the nature of the observed levels of damage and the observed differences between MEF Ogg1 +/+ and Ogg1 −/− genetic backgrounds, the genotoxic and oxidative DNA repair kinetics of 18-weeks exposed MEF cells were evaluated by the comet assay. Results indicate that MEF Ogg1 +/+ and Ogg1 −/− cells chronically exposed to i-As repair the DNA damage induced by arsenite, potassium bromide and UVC radiation less efficiently than control cells, being that observation clearly more pronounced in MEF Ogg1 −/− cells. Consequently, exposed cells accumulate a higher percentage of unrepaired DNA damage at the end of the repair period. As an attempt to eliminate i-As associated toxicity, chronically exposed MEF Ogg1 −/− cells overexpress the arsenic metabolizing enzyme As3mt. This adaptive response confers cells a significant resistance to i-As-induced cell death, but at expenses of accumulating high levels of DNA damage due to their repair impairment. Overall, the work presented here evidences that i-As chronic exposure disrupts the normal cellular repair function, and that oxidative DNA damage—and Ogg1 deficiency—exacerbates this phenomenon. The

  5. Reduced cellular DNA repair capacity after environmentally relevant arsenic exposure. Influence of Ogg1 deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Bach, Jordi; Peremartí, Jana; Annangi, Balasubramnayam [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona (Spain); Marcos, Ricard, E-mail: ricard.marcos@uab.es [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona (Spain); CIBER Epidemiología y Salud Pública, ISCIII, Madrid (Spain); Hernández, Alba, E-mail: alba.hernandez@uab.es [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona (Spain); CIBER Epidemiología y Salud Pública, ISCIII, Madrid (Spain)

    2015-09-15

    Highlights: • Repair ability under long-term exposure to arsenic was tested using the comet assay. • Effects were measured under Ogg1 wild-type and deficient backgrounds. • Exposed cells repair less efficiency the DNA damage induced by SA, KBrO{sub 3}, MMA{sup III} or UVC radiation. • Oxidative damage and Ogg1 deficient background exacerbate repair deficiencies. • Overexpression of the arsenic metabolizing enzyme As3mt acts as adaptive mechanism. - Abstract: Inorganic arsenic (i-As) is a genotoxic and carcinogenic environmental contaminant known to affect millions of people worldwide. Our previous work demonstrated that chronic sub-toxic i-As concentrations were able to induce biologically significant levels of genotoxic and oxidative DNA damage that were strongly influenced by the Ogg1 genotype. In order to study the nature of the observed levels of damage and the observed differences between MEF Ogg1{sup +/+} and Ogg1{sup −/−} genetic backgrounds, the genotoxic and oxidative DNA repair kinetics of 18-weeks exposed MEF cells were evaluated by the comet assay. Results indicate that MEF Ogg1{sup +/+} and Ogg1{sup −/−} cells chronically exposed to i-As repair the DNA damage induced by arsenite, potassium bromide and UVC radiation less efficiently than control cells, being that observation clearly more pronounced in MEF Ogg1{sup −/−} cells. Consequently, exposed cells accumulate a higher percentage of unrepaired DNA damage at the end of the repair period. As an attempt to eliminate i-As associated toxicity, chronically exposed MEF Ogg1{sup −/−} cells overexpress the arsenic metabolizing enzyme As3mt. This adaptive response confers cells a significant resistance to i-As-induced cell death, but at expenses of accumulating high levels of DNA damage due to their repair impairment. Overall, the work presented here evidences that i-As chronic exposure disrupts the normal cellular repair function, and that oxidative DNA damage—and Ogg1 deficiency

  6. Arsenic exposure triggers a shift in microRNA expression.

    Science.gov (United States)

    Sturchio, Elena; Colombo, Teresa; Boccia, Priscilla; Carucci, Nicoletta; Meconi, Claudia; Minoia, Claudio; Macino, Giuseppe

    2014-02-15

    Exposure to inorganic Arsenic (iAs) through drinking water is a major public health problem affecting most countries. iAs has been classified by the International Agency for Research on Cancer as Group 1: "Carcinogenic to humans". Although numerous studies have shown the related adverse effects of iAs, sensitive appropriate biomarkers for studies of environmental epidemiology are still required. The present work aims at investigate the role of microRNAs (miRNAs), powerful negative regulators of gene expression, playing a key role in many physiological and pathological cellular processes, in iAs exposure. To this end, we analyzed miRNA changes in expression profile triggered by iAs exposure in Jurkat cell line. We used microarray technology to profile the expression of miRNAs following 2 μmol/L sodium arsenite treatment at different time points. Moreover, we performed phenotypic analysis of iAs treated cells. Real Time Polymerase Chain Reaction (RT-PCR) was used to validate miRNA microarray data and to assay expression modulation of selected relevant mRNAs. Finally, bioinformatics techniques were applied to reconstruct iAs-relevant molecular pathways and miRNA regulatory networks from the expression data. We report miRNAs modulated after iAs treatment in Jurkat cells. In particular, we highlight 36 miRNAs exhibiting consistent dysregulation and particularly a panel of 8 miRNAs which we also validated by RT-PCR analysis. Computational analysis of lists of putative target genes for these 8 miRNAs points to an involvement in arsenic-response pathways, for a subset of them, that were analyzed by RT-PCR. Furthermore, iAs exposure reveals induction of cell cycle progression and the failure of apoptosis, supporting the idea of iAs carcinogenic activity. Our study provides a list of miRNAs whose expression levels are affected by iAs treatment, corroborating the importance of proceeding with the hunt for specific subset of miRNAs, which can serve as potential biomarkers of

  7. Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio development.

    Directory of Open Access Journals (Sweden)

    Laura M Beaver

    Full Text Available Zinc deficiency and chronic low level exposures to inorganic arsenic in drinking water are both significant public health concerns that affect millions of people including pregnant women. These two conditions can co-exist in the human population but little is known about their interaction, and in particular, whether zinc deficiency sensitizes individuals to arsenic exposure and toxicity, especially during critical windows of development. To address this, we utilized the Danio rerio (zebrafish model to test the hypothesis that parental zinc deficiency sensitizes the developing embryo to low-concentration arsenic toxicity, leading to altered developmental outcomes. Adult zebrafish were fed defined zinc deficient and zinc adequate diets and were spawned resulting in zinc adequate and zinc deficient embryos. The embryos were treated with environmentally relevant concentrations of 0, 50, and 500 ppb arsenic. Arsenic exposure significantly reduced the amount of zinc in the developing embryo by ~7%. The combination of zinc deficiency and low-level arsenic exposures did not sensitize the developing embryo to increased developmental malformations or mortality. The combination did cause a 40% decline in physical activity of the embryos, and this decline was significantly greater than what was observed with zinc deficiency or arsenic exposure alone. Significant changes in RNA expression of genes that regulate zinc homeostasis, response to oxidative stress and insulin production (including zip1, znt7, nrf2, ogg1, pax4, and insa were found in zinc deficient, or zinc deficiency and arsenic exposed embryos. Overall, the data suggests that the combination of zinc deficiency and arsenic exposure has harmful effects on the developing embryo and may increase the risk for developing chronic diseases like diabetes.

  8. Association of arsenic exposure with lung cancer incidence rates in the United States.

    Directory of Open Access Journals (Sweden)

    Joseph J Putila

    Full Text Available Although strong exposure to arsenic has been shown to be carcinogenic, its contribution to lung cancer incidence in the United States is not well characterized. We sought to determine if the low-level exposures to arsenic seen in the U.S. are associated with lung cancer incidence after controlling for possible confounders, and to assess the interaction with smoking behavior.Measurements of arsenic stream sediment and soil concentration obtained from the USGS National Geochemical Survey were combined, respectively, with 2008 BRFSS estimates on smoking prevalence and 2000 U.S. Census county level income to determine the effects of these factors on lung cancer incidence, as estimated from respective state-wide cancer registries and the SEER database. Poisson regression was used to determine the association between each variable and age-adjusted county-level lung cancer incidence. ANOVA was used to assess interaction effects between covariates.Sediment levels of arsenic were significantly associated with an increase in incident cases of lung cancer (P<0.0001. These effects persisted after controlling for smoking and income (P<0.0001. Across the U.S., exposure to arsenic may contribute to up to 5,297 lung cancer cases per year. There was also a significant interaction between arsenic exposure levels and smoking prevalence (P<0.05.Arsenic was significantly associated with lung cancer incidence rates in the U.S. after controlling for smoking and income, indicating that low-level exposure to arsenic is responsible for excess cancer cases in many parts of the U.S. Elevated county smoking prevalence strengthened the association between arsenic exposure and lung cancer incidence rate, an effect previously unseen on a population level.

  9. Estimating Inorganic Arsenic Exposure from U.S. Rice and Total Water Intakes

    OpenAIRE

    Mantha, Madhavi; Yeary, Edward; Trent, John; Creed, Patricia A.; Kubachka, Kevin; Hanley, Traci; Shockey, Nohora; Heitkemper, Douglas; Caruso, Joseph; Xue, Jianping; Rice, Glenn; Wymer, Larry; Creed, John T.

    2017-01-01

    Background: Among nonoccupationally exposed U.S. residents, drinking water and diet are considered primary exposure pathways for inorganic arsenic (iAs). In drinking water, iAs is the primary form of arsenic (As), while dietary As speciation techniques are used to differentiate iAs from less toxic arsenicals in food matrices. Objectives: Our goal was to estimate the distribution of iAs exposure rates from drinking water intakes and rice consumption in the U.S. population and ethnic- and age-b...

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

    Science.gov (United States)

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

    2015-08-01

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

  11. Total arsenic concentrations in toenails quantified by two techniques provide a useful biomarker of chronic arsenic exposure in drinking water

    International Nuclear Information System (INIS)

    Adair, Blakely M.; Hudgens, Edward E.; Schmitt, Michael T.; Calderon, Rebecca L.; Thomas, David J.

    2006-01-01

    Accurate quantitation of any contaminant of interest is critical for exposure assessment and metabolism studies that support risk assessment. A preliminary step in an arsenic exposure assessment study in Nevada quantified total arsenic (TAs) concentrations in tissues as biomarkers of exposure. Participants in this study (n=95) were at least 45 years old, had lived in the area for more than 20 years, and were exposed to a wide range of arsenic concentrations in drinking water (3-2100ppb). Concentrations of TAs in blood, urine, and toenails determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) ranged from below detection to 0.03, 0.76, and 12ppm, respectively; TAs in blood rarely exceeded the limit of detection. For comparison, TAs in toenails determined by neutron activation analysis (NAA) ranged from below detection to 16ppm. Significant (P 2 =0.3557 HG-AFS, adjusted r 2 =0.3922 NAA); TAs concentrations in urine were not described by drinking water As (adjusted r 2 =0.0170, P=0.1369). Analyses of TAs in toenails by HGAFS and NAA yielded highly concordant estimates (r=0.7977, P<0.0001). These results suggest that toenails are a better biomarker of chronic As exposure than urine in the current study, because the sequestration of As in toenails provides an integration of exposure over time that does not occur in urine

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

    Science.gov (United States)

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

    2007-05-01

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

  13. Cytogenetic insights into DNA damage and repair of lesions induced by a monomethylated trivalent arsenical

    Science.gov (United States)

    Arsenic is a human carcinogen, and only recently have animal models been developed that are useful in investigating its carcinogenic mode ofaction (MOA). However, how arsenic induces cancer is still an open question. In a previous paper, we proposed a model detailing how arsenic ...

  14. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway

    International Nuclear Information System (INIS)

    Ghosh, Jyotirmoy; Das, Joydeep; Manna, Prasenjit; Sil, Parames C.

    2009-01-01

    Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-κB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-κB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-κB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-κB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As-induced

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

    Science.gov (United States)

    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.

  16. A cross sectional study of anemia and iron deficiency as risk factors for arsenic-induced skin lesions in Bangladeshi women

    Directory of Open Access Journals (Sweden)

    Molly L. Kile

    2016-02-01

    Full Text Available Abstract Background In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions of people who rely on groundwater as their potable water source. The prevalence of anemia is also high in this region, particularly among women. Moreover, arsenic is known to affect heme synthesis and erythrocytes and the risk of arsenic-induced skin lesions appears to differ by sex. Methods We conducted a case-control study in 147 arsenic-exposed Bangladeshi women to assess the association between anemia and arsenic-induced skin lesions. Results We observed that the odds of arsenic-related skin lesions were approximately three times higher among women who were anemic (hemoglobin < 120 g/L compared to women with normal hemoglobin levels [Odds Ratio (OR = 3.32, 95 % Confidence Intervals (CI: 1.29, 8.52] after adjusting for arsenic levels in drinking water and other covariates. Furthermore, 75 % of the women with anemia had adequate iron stores (serum ferritin ≥12 μg/L, suggesting that the majority of anemia detected in this population was unrelated to iron depletion. Conclusions Considering the magnitude of arsenic exposure and prevalence of anemia in Bangladeshi women, additional research is warranted that identifies the causes of anemia so that effective interventions can be implemented while arsenic remediation efforts continue.

  17. Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: Review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

    International Nuclear Information System (INIS)

    Chen Yu; Parvez, Faruque; Gamble, Mary; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Graziano, Joseph H.; Ahsan, Habibul

    2009-01-01

    The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (> 300 μg/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 μg/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 μg/L, mean 99 μg/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention.

  18. Arsenic

    Science.gov (United States)

    ... for drinking-water quality Chemical hazards in drinking-water: arsenic Evaluations of the Joint FAO/WHO Expert Committee ... Africa Americas South-East Asia Europe Eastern Mediterranean Western ...

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    McClintock, Tyler R. [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Department of Urology, New York University School of Medicine, New York, NY (United States); Chen, Yu, E-mail: yu.chen@nyumc.org [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Parvez, Faruque [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY (United States); Makarov, Danil V. [Department of Urology, New York University School of Medicine, New York, NY (United States); Robert F. Wagner Graduate School of Public Service, New York University, New York, NY (United States); United States Department of Veterans Affairs Harbor Healthcare System, New York, NY (United States); New York University Cancer Institute, New York, NY (United States); Ge, Wenzhen [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam [U-Chicago Research Bangladesh, Ltd., Dhaka (Bangladesh); Slavkovich, Vesna [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY (United States); Bjurlin, Marc A. [Department of Urology, New York University School of Medicine, New York, NY (United States); Graziano, Joseph H. [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY (United States); and others

    2014-04-01

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

  1. Genetic polymorphisms in glutathione S-transferase (GST superfamily and risk of arsenic-induced urothelial carcinoma in residents of southwestern Taiwan

    Directory of Open Access Journals (Sweden)

    Hsueh Yu-Mei

    2011-07-01

    Full Text Available Abstract Background Arsenic exposure is an important public health issue worldwide. Dose-response relationship between arsenic exposure and risk of urothelial carcinoma (UC is consistently observed. Inorganic arsenic is methylated to form the metabolites monomethylarsonic acid and dimethylarsinic acid while ingested. Variations in capacity of xenobiotic detoxification and arsenic methylation might explain individual variation in susceptibility to arsenic-induced cancers. Methods To estimate individual susceptibility to arsenic-induced UC, 764 DNA specimens from our long-term follow-up cohort in Southwestern Taiwan were used and the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and arsenic methylation enzymes including GSTO1 and GSTO2 were genotyped. Results The GSTT1 null was marginally associated with increased urothelial carcinoma (UC risk (HR, 1.91, 95% CI, 1.00-3.65, while the association was not observed for other GSTs. Among the subjects with cumulative arsenic exposure (CAE ≥ 20 mg/L*year, the GSTT1 null genotype conferred a significantly increased cancer risk (RR, 3.25, 95% CI, 1.20-8.80. The gene-environment interaction between the GSTT1 and high arsenic exposure with respect to cancer risk was statistically significant (multiplicative model, p = 0.0151 and etiologic fraction was as high as 0.86 (95% CI, 0.51-1.22. The genetic effects of GSTO1/GSTO2 were largely confined to high arsenic level (CAE ≥ 20. Diplotype analysis showed that among subjects exposed to high levels of arsenic, the AGG/AGG variant of GSTO1 Ala140Asp, GSTO2 5'UTR (-183A/G, and GSTO2 Asn142Asp was associated with an increased cancer risk (HRs, 4.91, 95% CI, 1.02-23.74 when compared to the all-wildtype reference, respectively. Conclusions The GSTs do not play a critical role in arsenic-induced urothelial carcinogenesis. The genetic effects of GSTT1 and GSTO1 on arsenic-induced urothelial carcinogenesis are largely confined to very high exposure level.

  2. Arsenic Exposure and Type 2 Diabetes: MicroRNAs as Mechanistic Links?

    OpenAIRE

    Beck, Rowan; Styblo, Miroslav; Sethupathy, Praveen

    2017-01-01

    Purpose of Review The goal of this review is to delineate the following: (1) the primary means of inorganic arsenic (iAs) exposure for human populations, (2) the adverse public health outcomes associated with chronic iAs exposure, (3) the pathophysiological connection between arsenic and type 2 diabetes (T2D), and (4) the incipient evidence for microRNAs as candidate mechanistic links between iAs exposure and T2D. Recent Findings Exposure to iAs in animal models has been associated with the d...

  3. Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

    Directory of Open Access Journals (Sweden)

    Benjamin C Thompson

    Full Text Available Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV radiation and affects DNA damage and repair. Nicotinamide (vitamin B3 reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2 solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.

  4. Acute, but not Chronic, Exposure to Arsenic Provokes Glucose Intolerance in Rats: Possible Roles for Oxidative Stress and the Adrenergic Pathway.

    Science.gov (United States)

    Rezaei, Mohsen; Khodayar, Mohammd Javad; Seydi, Enayatollah; Soheila, Alboghobeish; Parsi, Isa Kazemzadeh

    2017-06-01

    Health problems due to heavy metals have become a worldwide concern. Along with its carcinogenicity, arsenic exposure results in impairment of glucose metabolism and insulin secretion as well as altered gene expression and signal transduction. However, the exact mechanism behind the behaviour of arsenic on glucose homeostasis and insulin secretion has not yet been fully understood. Fasting blood sugar and glucose tolerance tests were evaluated. In this study, we demonstrated that arsenic, when acutely administered, induced glucose intolerance in rats, although its chronic oral exposure did not provoke any glucose intolerance or hyperglycemia in rats. The protective activity of N-acetylcysteine, carvedilol and propranolol in male rats exposed to arsenic were also assessed, and N-acetylcysteine, particularly at 40 and 80 mg/kg, prevented the glucose intolerance induced in rats by arsenic. The present study showed that acute, but not chronic, contact with arsenic generates significant changes in the normal glucose tolerance pattern that may be due fundamentally to overproduction of reactive oxygen species and oxidative stress and is preventable by using N-acetylcysteine, a thiol-containing antioxidant. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  5. Low-level arsenic exposure via drinking water consumption and female fecundity - A preliminary investigation

    International Nuclear Information System (INIS)

    Susko, Michele L.; Bloom, Michael S.; Neamtiu, Iulia A.; Appleton, Allison A.; Surdu, Simona; Pop, Cristian; Fitzgerald, Edward F.; Anastasiu, Doru

    2017-01-01

    High level arsenic exposure is associated with reproductive toxicity in experimental and observational studies; however, few data exist to assess risks at low levels. Even less data are available to evaluate the impact of low level arsenic exposure on human fecundity. Our aim in this pilot study was a preliminary evaluation of associations between low level drinking water arsenic contamination and female fecundity. This retrospective study was conducted among women previously recruited to a hospital-based case-control study of spontaneous pregnancy loss in Timiá¹£ County, Romania. Women (n=94) with planned pregnancies of 5–20 weeks gestation completed a comprehensive physician-administered study questionnaire and reported the number of menstrual cycles attempting to conceive as the time to pregnancy (TTP). Drinking water samples were collected from residential drinking water sources and we determined arsenic levels using hydride generation-atomic absorption spectrometry (HG-AAS). Multivariable Cox-proportional hazards regression with Efron approximation was employed to evaluate TTP as a function of drinking water arsenic concentrations among planned pregnancies, adjusted for covariates. There was no main effect for drinking water arsenic exposure, yet the conditional probability for pregnancy was modestly lower among arsenic exposed women with longer TTPs, relative to women with shorter TTPs, and relative to unexposed women. For example, 1 µg/L average drinking water arsenic conferred 5%, 8%, and 10% lower likelihoods for pregnancy in the 6th, 9th, and 12th cycles, respectively (P=0.01). While preliminary, our results suggest that low level arsenic contamination in residential drinking water sources may further impair fecundity among women with longer waiting times; however, this hypothesis requires confirmation by a future, more definitive study. - Highlights: • We assessed low level drinking water arsenic as a predictor of fecundability. • Arsenic did

  6. Low-level arsenic exposure via drinking water consumption and female fecundity - A preliminary investigation

    Energy Technology Data Exchange (ETDEWEB)

    Susko, Michele L. [Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York (United States); Bloom, Michael S., E-mail: mbloom@albany.edu [Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York (United States); Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, New York (United States); Neamtiu, Iulia A. [Health Department, Environmental Health Center, Cluj-Napoca (Romania); IMOGEN Research Institute, Cluj-Napoca (Romania); Appleton, Allison A. [Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York (United States); Surdu, Simona [Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, New York (United States); Pop, Cristian [Physico-chemical and Biotoxicological Analysis Laboratory, Environmental Health Center, Cluj-Napoca (Romania); Cluj School of Public Health - College of Political, Administrative and Communication Sciences, Babeș-Bolyai University, Cluj-Napoca (Romania); Faculty of Environmental Science and Engineering, Babeș-Bolyai University, Cluj-Napoca (Romania); Fitzgerald, Edward F. [Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York (United States); Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, New York (United States); Anastasiu, Doru [University of Medicine and Pharmacy “Victor Babeș”, Timișoara (Romania); Obstetrics and Gynecology Department of the Emergency County Hospital, Timișoara (Romania); and others

    2017-04-15

    High level arsenic exposure is associated with reproductive toxicity in experimental and observational studies; however, few data exist to assess risks at low levels. Even less data are available to evaluate the impact of low level arsenic exposure on human fecundity. Our aim in this pilot study was a preliminary evaluation of associations between low level drinking water arsenic contamination and female fecundity. This retrospective study was conducted among women previously recruited to a hospital-based case-control study of spontaneous pregnancy loss in Timiá¹£ County, Romania. Women (n=94) with planned pregnancies of 5–20 weeks gestation completed a comprehensive physician-administered study questionnaire and reported the number of menstrual cycles attempting to conceive as the time to pregnancy (TTP). Drinking water samples were collected from residential drinking water sources and we determined arsenic levels using hydride generation-atomic absorption spectrometry (HG-AAS). Multivariable Cox-proportional hazards regression with Efron approximation was employed to evaluate TTP as a function of drinking water arsenic concentrations among planned pregnancies, adjusted for covariates. There was no main effect for drinking water arsenic exposure, yet the conditional probability for pregnancy was modestly lower among arsenic exposed women with longer TTPs, relative to women with shorter TTPs, and relative to unexposed women. For example, 1 µg/L average drinking water arsenic conferred 5%, 8%, and 10% lower likelihoods for pregnancy in the 6th, 9th, and 12th cycles, respectively (P=0.01). While preliminary, our results suggest that low level arsenic contamination in residential drinking water sources may further impair fecundity among women with longer waiting times; however, this hypothesis requires confirmation by a future, more definitive study. - Highlights: • We assessed low level drinking water arsenic as a predictor of fecundability. • Arsenic did

  7. Low-level arsenic exposure via drinking water consumption and female fecundity - A preliminary investigation.

    Science.gov (United States)

    Susko, Michele L; Bloom, Michael S; Neamtiu, Iulia A; Appleton, Allison A; Surdu, Simona; Pop, Cristian; Fitzgerald, Edward F; Anastasiu, Doru; Gurzau, Eugen S

    2017-04-01

    High level arsenic exposure is associated with reproductive toxicity in experimental and observational studies; however, few data exist to assess risks at low levels. Even less data are available to evaluate the impact of low level arsenic exposure on human fecundity. Our aim in this pilot study was a preliminary evaluation of associations between low level drinking water arsenic contamination and female fecundity. This retrospective study was conducted among women previously recruited to a hospital-based case-control study of spontaneous pregnancy loss in Timiṣ County, Romania. Women (n=94) with planned pregnancies of 5-20 weeks gestation completed a comprehensive physician-administered study questionnaire and reported the number of menstrual cycles attempting to conceive as the time to pregnancy (TTP). Drinking water samples were collected from residential drinking water sources and we determined arsenic levels using hydride generation-atomic absorption spectrometry (HG-AAS). Multivariable Cox-proportional hazards regression with Efron approximation was employed to evaluate TTP as a function of drinking water arsenic concentrations among planned pregnancies, adjusted for covariates. There was no main effect for drinking water arsenic exposure, yet the conditional probability for pregnancy was modestly lower among arsenic exposed women with longer TTPs, relative to women with shorter TTPs, and relative to unexposed women. For example, 1µg/L average drinking water arsenic conferred 5%, 8%, and 10% lower likelihoods for pregnancy in the 6th, 9th, and 12th cycles, respectively (P=0.01). While preliminary, our results suggest that low level arsenic contamination in residential drinking water sources may further impair fecundity among women with longer waiting times; however, this hypothesis requires confirmation by a future, more definitive study. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Transplacental and early life exposure to inorganic arsenic affected development and behavior in offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Shuhua; Jin, Yaping; Sun, Guifan [China Medical University, Department of Environmental and Occupational Health, College of Public Health, Shenyang, Liaoning (China); Sun, Wenjuan; Wang, Fengzhi [Shenyang Medical College, Department of Preventive Medicine, Shenyang, Liaoning (China)

    2009-06-15

    To evaluate the developmental neurotoxicity of arsenic in offspring rats by transplacental and early life exposure to sodium arsenite in drinking water, the pregnant rats or lactating dams, and weaned pups were given free access to drinking water, which contained arsenic at concentrations of 0, 10, 50, 100 mg/L from GD 6 until PND 42. A battery of physical and behavioral tests was applied to evaluate the functional outcome of pups. Pups in arsenic exposed groups weighed less than controls throughout lactation and weaning. Body weight of 10, 50 and 100 mg/L arsenic exposed groups decreased significantly on PND 42, 16 and 12, respectively. Physical development (pinna unfolding, fur appearance, incisor eruption, or eye opening) in pups displayed no significant differences between control and arsenic treated groups. The number of incidences within the 100 mg/L arsenic treated group, in tail hung, auditory startle and visual placing showed significant decrease compared to the control group (p<0.05). In square water maze test, the trained numbers to finish the trials successfully in 50 and 100 mg/L arsenic exposed groups increased remarkably compared to control group, and there was a dose-related increase (p<0.01) observed. Taken together, these data show that exposure of inorganic arsenite to pregnant dams and offspring pups at levels up to 100 mg/L in drinking water may affect their learning and memory functions and neuromotor reflex. (orig.)

  9. In utero and early life arsenic exposure in relation to long-term health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Farzan, Shohreh F.; Karagas, Margaret R. [Children' s Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, NH 03755 (United States); Section of Biostatistics and Epidemiology, Department of Community and Family Medicine and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 (United States); Chen, Yu, E-mail: yu.chen@nyumc.org [Department of Population Health, New York University School of Medicine, New York, NY 10016 (United States)

    2013-10-15

    Background: There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications. Objectives: Our goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models. Methods: We examined the current literature and identified relevant studies through PubMed by using combinations of the search terms “arsenic”, “in utero”, “transplacental”, “prenatal” and “fetal”. Discussion: Ecological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects. Conclusions: As millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels. - Highlights: • We review in utero and early-life As exposure impacts on lifelong disease risks. • Evidence indicates that early-life As increases risks of lung disease, cancer and CVD. • Animal work largely parallels human studies and may lead to new research directions. • Prospective studies and individual exposure assessments with biomarkers are needed. • Assessing intermediary

  10. In utero and early life arsenic exposure in relation to long-term health and disease

    International Nuclear Information System (INIS)

    Farzan, Shohreh F.; Karagas, Margaret R.; Chen, Yu

    2013-01-01

    Background: There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications. Objectives: Our goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models. Methods: We examined the current literature and identified relevant studies through PubMed by using combinations of the search terms “arsenic”, “in utero”, “transplacental”, “prenatal” and “fetal”. Discussion: Ecological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects. Conclusions: As millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels. - Highlights: • We review in utero and early-life As exposure impacts on lifelong disease risks. • Evidence indicates that early-life As increases risks of lung disease, cancer and CVD. • Animal work largely parallels human studies and may lead to new research directions. • Prospective studies and individual exposure assessments with biomarkers are needed. • Assessing intermediary endpoints may

  11. The Role of Arsenic Speciation in Dietary Exposure Assessment and the Need to Include Bioaccessibility and Biotransformation

    Science.gov (United States)

    Chemical form specific exposure assessment for arsenic has long been identified as a source of uncertainty in estimating the risk associated with the aggregate exposure for a population. Some speciation based assessments document occurrence within an exposure route; however, the...

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Contribution of breast milk and formula to arsenic exposure during the first year of life in a US prospective cohort.

    Science.gov (United States)

    Carignan, Courtney C; Karagas, Margaret R; Punshon, Tracy; Gilbert-Diamond, Diane; Cottingham, Kathryn L

    2016-09-01

    Arsenic is a carcinogen that can also affect the cardiac, respiratory, neurological and immune systems. Children have higher dietary arsenic exposure than adults owing to their more restricted diets and greater intake per unit body mass. We evaluated the potential contributions of breast milk and formula to arsenic exposure throughout the first year of life for 356 infants in the prospective New Hampshire Birth Cohort Study (NHBCS) using infant diets reported by telephone at 4, 8 and 12 months of age; measured household water arsenic concentrations; and literature data. Based on our central-tendency models, population-wide geometric mean (GM) estimated arsenic exposures in the NHBCS were relatively low, decreasing from 0.1 μg/kg/day at 4 months of age to 0.07 μg/kg/day at 12 months of age. At all three time points, exclusively formula-fed infants had GM arsenic exposures ~8 times higher than exclusively breastfed infants owing to arsenic in both tap water and formula powder. Estimated maximum exposures reached 9 μg/kg/day among exclusively formula-fed infants in households with high tap water arsenic (80 μg/l). Overall, modeled arsenic exposures via breast milk and formula were low throughout the first year of life, unless formula was prepared with arsenic-contaminated tap water.

  14. Why Does Exposure to Arsenic from Drinking Groundwater in Asian Megadeltas Continue to be High?

    Science.gov (United States)

    van Geen, A.; Ahmed, K. M.; Ahmed, E. B.; Choudhury, I.; Mozumder, M. R. H.; Bostick, B. C.; Mailloux, B. J.; Knappett, P. S.; Schlosser, P.

    2014-12-01

    Concentrations of arsenic in groundwater pumped from a significant fraction of the millions of shallow tubewells installed, mostly privately, across S/SE Asia exceed the WHO guideline value of 10 ug/L by a factor of 10 to 100. The resulting exposure has been linked to cancers and cardio-vascular disease in adults and inhibited intellectual function in children. In Bangladesh, the most affected country, the impact of early mitigation efforts relying on water treatment has been limited by the cost and logistics of maintenance. A simpler approach based on switching human consumption to low-arsenic wells has proved to be more resilient although it remains far from sufficiently adopted. A decade ago, there was concern that low-arsenic wells might become contaminated upon use. Observations and modeling have since shown that groundwater arsenic concentrations are likely to rise only in certain hydrogeologically vulnerable areas and then only gradually. Our recently completed blanket-testing campaign of 50,000 wells in 300 villages of Bangladesh has shown that, instead, a leading cause of current exposure is that households have continued to install wells and typically have nowhere to turn for a reliable arsenic test. The same campaign has shown that another reason for continued exposure is that deeper wells that are low in arsenic and whose installation has been subsidized by the Bangladesh government are not located to maximize public access. The geographic clustering of these deep wells suggests that, all too often, their location is decided on the basis of political allegiance rather than need. Such obstacles to lowering arsenic exposure might be overcome with more widespread testing and the public posting of maps of test results also showing where deep wells have been installed. We will show that obtaining and sharing such information has been greatly facilitated by a reliable field-kit for arsenic and the increasing use of smartphones in Bangladesh.

  15. A Prospective Study of Arsenic Exposure From Drinking Water and Incidence of Skin Lesions in Bangladesh

    Science.gov (United States)

    Argos, Maria; Kalra, Tara; Pierce, Brandon L.; Chen, Yu; Parvez, Faruque; Islam, Tariqul; Ahmed, Alauddin; Hasan, Rabiul; Hasan, Khaled; Sarwar, Golam; Levy, Diane; Slavkovich, Vesna; Graziano, Joseph H.; Rathouz, Paul J.; Ahsan, Habibul

    2011-01-01

    Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. The authors aimed to evaluate the association between arsenic exposure and skin lesion incidence among participants in the Health Effects of Arsenic Longitudinal Study (HEALS). The analyses used data on 10,182 adults free of skin lesions at baseline through the third biennial follow-up of the cohort (2000–2009). Discrete-time hazard regression models were used to estimate hazard ratios and 95% confidence intervals for incident skin lesions. Multivariate-adjusted hazard ratios for incident skin lesions comparing 10.1–50.0, 50.1–100.0, 100.1–200.0, and ≥200.1 μg/L with ≤10.0 μg/L of well water arsenic exposure were 1.17 (95% confidence interval (CI): 0.92, 1.49), 1.69 (95% CI: 1.33, 2.14), 1.97 (95% CI: 1.58, 2.46), and 2.98 (95% CI: 2.40, 3.71), respectively (Ptrend = 0.0001). Results were similar for the other measures of arsenic exposure, and the increased risks remained unchanged with changes in exposure in recent years. Dose-dependent associations were more pronounced in females, but the incidence of skin lesions was greater in males and older individuals. Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L). PMID:21576319

  16. Biomarkers of Exposure: A Case Study with Inorganic Arsenic

    OpenAIRE

    Hughes, Michael F.

    2006-01-01

    The environmental contaminant inorganic arsenic (iAs) is a human toxicant and carcinogen. Most mammals metabolize iAs by reducing it to trivalency, followed by oxidative methylation to pentavalency. iAs and its methylated metabolites are primarily excreted in urine within 4–5 days by most species and have a relatively low rate of bioaccumulation. Intra- and interindividual differences in the methylation of iAs may affect the adverse health effects of arsenic. Both inorganic and organic trival...

  17. Arsenic exposure in pregnant mice disrupts placental vasculogenesis and causes spontaneous abortion.

    Science.gov (United States)

    He, Wenjie; Greenwell, Robert J; Brooks, Diane M; Calderón-Garcidueñas, Lilian; Beall, Howard D; Coffin, J Douglas

    2007-09-01

    Arsenic is an abundant toxicant in ground water and soil around areas with extractive industries. Human epidemiological studies have shown that arsenic exposure is linked to developmental defects and miscarriage. The placenta is known to utilize vasculogenesis to develop its circulation. The hypothesis tested here states the following: arsenic exposure causes placental dysmorphogenesis and defective placental vasculogenesis resulting in placental insufficiency and subsequent spontaneous abortion. To test this hypothesis, pregnant mice were exposed to sodium arsenite (AsIII) through drinking water from conception through weanling stages. Neonatal assessment of birth rates, pup weights, and litter sizes in arsenic exposed and control mothers revealed that AsIII-exposed mothers had only 40% the fecundity of controls. Preterm analysis at E12.5 revealed a loss of fecundity at E12.5 from either 20 ppm or greater exposures to AsIII. There was no loss of fecundity at E7.5 suggesting that spontaneous abortion occurs during placentation. Histomorphometry on E12.5 placentae from arsenic-exposed mice revealed placental dysplasia especially in the vasculature. These results suggest that arsenic toxicity is causative for mammalian spontaneous abortion by virtue of aberrant placental vasculogenesis and placental insufficiency.

  18. Long-term exposure to low-level arsenic in drinking water and diabetes incidence

    DEFF Research Database (Denmark)

    Bräuner, Elvira Vaclavik; Nordsborg, Rikke Baastrup; Andersen, Zorana Jovanovic

    2014-01-01

    BACKGROUND: Established causes of diabetes do not fully explain the present epidemic. High-level arsenic exposure has been implicated in diabetes risk, but the effect of low-level arsenic exposure in drinking water remains unclear. OBJECTIVE: We sought to determine whether long-term exposure to low......-level arsenic in drinking water in Denmark is associated with an increased risk of diabetes using a large prospective cohort. METHODS: During 1993-1997, we recruited 57,053 persons. We followed each cohort member for diabetes occurrence from enrollment until 31 December 2006. We traced and geocoded residential...... exposure and diabetes incidence, separately for two definitions of diabetes: all cases and a more strict definition in which cases of diabetes based solely on blood glucose results were excluded. RESULTS: Over a mean follow-up period of 9.7 years for 52,931 eligible participants, there were a total of 4...

  19. Oligofructose protects against arsenic-induced liver injury in a model of environment/obesity interaction

    Energy Technology Data Exchange (ETDEWEB)

    Massey, Veronica L. [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Stocke, Kendall S. [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Schmidt, Robin H.; Tan, Min [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Ajami, Nadim [Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX (United States); Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX (United States); Neal, Rachel E. [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Petrosino, Joseph F. [Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX (United States); Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX (United States); Barve, Shirish [Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Arteel, Gavin E., E-mail: gavin.arteel@louisville.edu [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States)

    2015-05-01

    Arsenic (As) tops the ATSDR list of hazardous environmental chemicals and is known to cause liver injury. Although the concentrations of As found in the US water supply are generally too low to directly damage the liver, subhepatotoxic doses of As sensitize the liver to experimental NAFLD. It is now suspected that GI microbiome dysbiosis plays an important role in development of NALFD. Importantly, arsenic has also been shown to alter the microbiome. The purpose of the current study was to test the hypothesis that the prebiotic oligofructose (OFC) protects against enhanced liver injury caused by As in experimental NAFLD. Male C57Bl6/J mice were fed low fat diet (LFD), high fat diet (HFD), or HFD containing oligofructose (OFC) during concomitant exposure to either tap water or As-containing water (4.9 ppm as sodium arsenite) for 10 weeks. HFD significantly increased body mass and caused fatty liver injury, as characterized by an increased liver weight-to-body weight ratio, histologic changes and transaminases. As observed previously, As enhanced HFD-induced liver damage, which was characterized by enhanced inflammation. OFC supplementation protected against the enhanced liver damage caused by As in the presence of HFD. Interestingly, arsenic, HFD and OFC all caused unique changes to the gut flora. These data support previous findings that low concentrations of As enhance liver damage caused by high fat diet. Furthermore, these results indicate that these effects of arsenic may be mediated, at least in part, by GI tract dysbiosis and that prebiotic supplementation may confer significant protective effects. - Highlights: • Arsenic (As) enhances liver damage caused by a high-fat (HFD) diet in mice. • Oligofructose protects against As-enhanced liver damage caused by HFD. • As causes dysbiosis in the GI tract and exacerbates the dysbiosis caused by HFD. • OFC prevents the dysbiosis caused by HFD and As, increasing commensal bacteria.

  20. Oligofructose protects against arsenic-induced liver injury in a model of environment/obesity interaction

    International Nuclear Information System (INIS)

    Massey, Veronica L.; Stocke, Kendall S.; Schmidt, Robin H.; Tan, Min; Ajami, Nadim; Neal, Rachel E.; Petrosino, Joseph F.; Barve, Shirish; Arteel, Gavin E.

    2015-01-01

    Arsenic (As) tops the ATSDR list of hazardous environmental chemicals and is known to cause liver injury. Although the concentrations of As found in the US water supply are generally too low to directly damage the liver, subhepatotoxic doses of As sensitize the liver to experimental NAFLD. It is now suspected that GI microbiome dysbiosis plays an important role in development of NALFD. Importantly, arsenic has also been shown to alter the microbiome. The purpose of the current study was to test the hypothesis that the prebiotic oligofructose (OFC) protects against enhanced liver injury caused by As in experimental NAFLD. Male C57Bl6/J mice were fed low fat diet (LFD), high fat diet (HFD), or HFD containing oligofructose (OFC) during concomitant exposure to either tap water or As-containing water (4.9 ppm as sodium arsenite) for 10 weeks. HFD significantly increased body mass and caused fatty liver injury, as characterized by an increased liver weight-to-body weight ratio, histologic changes and transaminases. As observed previously, As enhanced HFD-induced liver damage, which was characterized by enhanced inflammation. OFC supplementation protected against the enhanced liver damage caused by As in the presence of HFD. Interestingly, arsenic, HFD and OFC all caused unique changes to the gut flora. These data support previous findings that low concentrations of As enhance liver damage caused by high fat diet. Furthermore, these results indicate that these effects of arsenic may be mediated, at least in part, by GI tract dysbiosis and that prebiotic supplementation may confer significant protective effects. - Highlights: • Arsenic (As) enhances liver damage caused by a high-fat (HFD) diet in mice. • Oligofructose protects against As-enhanced liver damage caused by HFD. • As causes dysbiosis in the GI tract and exacerbates the dysbiosis caused by HFD. • OFC prevents the dysbiosis caused by HFD and As, increasing commensal bacteria

  1. Predicting arsenic concentrations in groundwater of San Luis Valley, Colorado: implications for individual-level lifetime exposure assessment.

    Science.gov (United States)

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

    2014-08-01

    Consumption of inorganic arsenic in drinking water at high levels has been associated with chronic diseases. Risk is less clear at lower levels of arsenic, in part due to difficulties in estimating exposure. Herein we characterize spatial and temporal variability of arsenic concentrations and develop models for predicting aquifer arsenic concentrations in the San Luis Valley, Colorado, an area of moderately elevated arsenic in groundwater. This study included historical water samples with total arsenic concentrations from 595 unique well locations. A longitudinal analysis established temporal stability in arsenic levels in individual wells. The mean arsenic levels for a random sample of 535 wells were incorporated into five kriging models to predict groundwater arsenic concentrations at any point in time. A separate validation dataset (n = 60 wells) was used to identify the model with strongest predictability. Findings indicate that arsenic concentrations are temporally stable (r = 0.88; 95 % CI 0.83-0.92 for samples collected from the same well 15-25 years apart) and the spatial model created using ordinary kriging best predicted arsenic concentrations (ρ = 0.72 between predicted and observed validation data). These findings illustrate the value of geostatistical modeling of arsenic and suggest the San Luis Valley is a good region for conducting epidemiologic studies of groundwater metals because of the ability to accurately predict variation in groundwater arsenic concentrations.

  2. Total and inorganic arsenic in fish, seafood and seaweeds--exposure assessment.

    Science.gov (United States)

    Mania, Monika; Rebeniak, Małgorzata; Szynal, Tomasz; Wojciechowska-Mazurek, Maria; Starska, Krystyna; Ledzion, Ewa; Postupolski, Jacek

    2015-01-01

    According to the European Food Safety Authority (EFSA), fish, seafood and seaweeds are foodstuffs that significantly contribute to dietary arsenic intake. With the exception of some algal species, the dominant compounds of arsenic in such food products are the less toxic organic forms. Both the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and EFSA recommend that speciation studies be performed to determine the different chemical forms in which arsenic is present in food due to the differences in their toxicity. Knowing such compositions can thus enable a complete exposure assessment to be made. Determination of total and inorganic arsenic contents in fish, their products, seafood and seaweeds present on the Polish market. This was then followed by an exposure assessment of consumers to inorganic arsenic in these foodstuffs. Total and inorganic arsenic was determined in 55 samples of fish, their products, seafood as well as seaweeds available on the market. The analytical method was hydride generation atomic absorption spectrometry (HGAAS), after dry ashing of samples and reduction of arsenic to arsenic hydride using sodium borohydride. In order to isolate only the inorganic forms of arsenic prior to mineralisation, samples were subjected to concentrated HCl hydrolysis, followed by reduction with hydrobromic acid and hydrazine sulphate after which triple chloroform extractions and triple 1M HCl re-extractions were performed. Exposure of adults was estimated in relation to the Benchmark Dose Lower Confidence Limit (BMDL0.5) as set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) that resulted in a 0.5% increase in lung cancer (3.0 μg/kg body weight (b.w.) per day). Mean total arsenic content from all investigated fish samples was 0.46 mg/kg (90th percentile 0.94 mg/kg), whilst the inorganic arsenic content never exceeded the detection limit of the analytical method used (0.025 mg/kg). In fish products, mean total arsenic concentration was

  3. A Systematic Review of Arsenic Exposure and Its Social and Mental Health Effects with Special Reference to Bangladesh

    Directory of Open Access Journals (Sweden)

    Alexander Kraemer

    2009-05-01

    Full Text Available Undergroundwater in many regions of the world is contaminated with high concentrations of arsenic and the resulting toxicity has created a major environmental and public health problem in the affected regions. Chronic arsenic exposure can cause many diseases, including various physical and psychological harms. Although the physical problems caused by arsenic toxicity are well reported in literature, unfortunately the consequences of arsenic exposure on mental health are not adequately studied. Therefore we conducted a review of the available literature focusing on the social consequences and detrimental effects of arsenic toxicity on mental health. Chronic arsenic exposures have serious implications for its victims (i.e. arsenicosis patients and their families including social instability, social discrimination, refusal of victims by community and families, and marriage-related problems. Some studies conducted in arsenic affected areas revealed that arsenic exposures are associated with various neurologic problems. Chronic arsenic exposure can lead to mental retardation and developmental disabilities such as physical, cognitive, psychological, sensory and speech impairments. As health is defined by the World Health Organization as “a state of complete physical, mental and social wellbeing”, the social dimensions have a large impact on individual’s mental health. Furthermore studies in China und Bangladesh have shown that mental health problems (e.g. depression are more common among the people affected by arsenic contamination. Our study indicates various neurological, mental and social consequences among arsenic affected victims. Further studies are recommended in arsenic-affected areas to understand the underlying mechanisms of poor mental health caused by arsenic exposure.

  4. Study of arsenic accumulation in rice and evaluation of protective effects of Chorchorus olitorius leaves against arsenic contaminated rice induced toxicities in Wistar albino rats.

    Science.gov (United States)

    Hosen, Saeed Mohammed Imran; Das, Dipesh; Kobi, Rupkanowar; Chowdhury, Dil Umme Salma; Alam, Md Jibran; Rudra, Bashudev; Bakar, Muhammad Abu; Islam, Saiful; Rahman, Zillur; Al-Forkan, Mohammad

    2016-10-14

    In the present study, we investigated the arsenic accumulation in different parts of rice irrigated with arsenic contaminated water. Besides, we also evaluated the protective effects of Corchorus olitorius leaves against arsenic contaminated rice induced toxicities in animal model. A pot experiment was conducted with arsenic amended irrigation water (0.0, 25.0, 50.0 and 75.0 mg/L As) to investigate the arsenic accumulation in different parts of rice. In order to evaluate the protective effects of Corchorus olitorius leaves, twenty Wistar albino rats were divided into four different groups. The control group (Group-I) was supplied with normal laboratory pellets while groups II, III, and IV received normal laboratory pellets supplemented with arsenic contaminated rice, C. olitorius leaf powder (4 %), arsenic contaminated rice plus C. olitorius leaf powder (4 %) respectively. Different haematological parameters and serum indices were analyzed to evaluate the protective effects of Corchorus olitorius leaves against arsenic intoxication. To gather more supportive evidences of Corchorus olitorius potentiality against arsenic intoxication, histopathological analysis of liver, kidney, spleen and heart tissues was also performed. From the pot experiment, we have found a significant (p ≤ 0.05) increase of arsenic accumulation in different parts of rice with the increase of arsenic concentrations in irrigation water and the trend of accumulation was found as root > straw > husk > grain. Another part of the experiment revealed that supplementation of C. olitorius leaves with arsenic contaminated rice significantly (p rice induced toxicities. Arsenic accumulation in different parts of rice increased dose-dependently. Hence, for irrigation purpose arsenic contaminated water cannot be used. Furthermore, arsenic contaminated rice induced several toxicities in animal model, most of which could be minimized with the food supplementation of Corchorus olitorius

  5. Modulatory role of dietary Chlorella vulgaris powder against arsenic-induced immunotoxicity and oxidative stress in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Zahran, Eman; Risha, Engy

    2014-12-01

    Arsenic intoxicant have long been regarded as an impending carcinogenic, genotoxic, and immunotoxic heavy metal to human and animals as well. In this respect, we evaluated biomarkers of the innate immune response and oxidative stress metabolism in gills and liver of Nile tilapia (Oreochromis niloticus) after arsenic exposure, and the protective role of Chlorella vulgaris (Ch) dietary supplementation were elucidated. Protective role of C. vulgaris (Ch), as supplementary feeds (5% and 10% of the diet) was studied in Nile tilapia (O. niloticus) against arsenic induced toxicity (NaAsO2 at 7 ppm) for 21 days exposure period. A significant down-regulation in innate immune response; including, respiratory burst, lysozyme, and bactericidal activity followed due to deliberately As(+3) exposure. Similarly, oxidative stress response; like nitric oxide (NO), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels were significantly decreased. Combined treatment of Ch and As(+3) significantly enhanced the innate immune response and antioxidant activity. Strikingly, Ch supplementation at 10% has been considered the optimum for Nile tilapia since it exhibited enhancement of innate immune response and antioxidant activity over the level 5%, and even better than that of control level. Thus, our results concluded that dietary Ch supplementation could protect Nile tilapia against arsenic induced immunosuppression and oxidative stresses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Influence of cooking method on arsenic retention in cooked rice related to dietary exposure.

    Science.gov (United States)

    Rahman, M Azizur; Hasegawa, H; Rahman, M Arifur; Rahman, M Mahfuzur; Miah, M A Majid

    2006-10-15

    Arsenic concentration in raw rice is not only the determinant in actual dietary exposure. Though there have been many reports on arsenic content in raw rice and different tissues of rice plant, little is known about arsenic content retained in cooked rice after being cooked following the traditional cooking methods employed by the people of arsenic epidemic areas. A field level experiment was conducted in Bangladesh to investigate the influence of cooking methods on arsenic retention in cooked rice. Rice samples were collected directly from a severely arsenic affected area and also from an unaffected area, to compare the results. Rice was cooked according to the traditional methods employed by the population of subjected areas. Arsenic concentrations were 0.40+/-0.03 and 0.58+/-0.12 mg/kg in parboiled rice of arsenic affected area, cooked with excess water and 1.35+/-0.04 and 1.59+/-0.07 mg/kg in gruel for BRRI dhan28 and BRRI hybrid dhan1, respectively. In non-parboiled rice, arsenic concentrations were 0.39+/-0.04 and 0.44+/-0.03 mg/kg in rice cooked with excess water and 1.62+/-0.07 and 1.74+/-0.05 mg/kg in gruel for BRRI dhan28 and BRRI hybrid dhan1, respectively. Total arsenic content in rice, cooked with limited water (therefore gruel was absorbed completely by rice) were 0.89+/-0.07 and 1.08+/-0.06 mg/kg (parboiled) and 0.75+/-0.04 and 1.09+/-0.06 mg/kg (non-parboiled) for BRRI dhan28 and BRRI hybrid dhan1, respectively. Water used for cooking rice contained 0.13 and 0.01 mg of As/l for contaminated and non-contaminated areas, respectively. Arsenic concentrations in cooked parboiled and non-parboiled rice and gruel of non-contaminated area were significantly lower (p<0.01) than that of contaminated area. The results imply that cooking of arsenic contaminated rice with arsenic contaminated water increases its concentration in cooked rice.

  7. Cortex and hippocampus DNA epigenetic response to a long-term arsenic exposure via drinking water.

    Science.gov (United States)

    Du, Xiaoyan; Tian, Meiping; Wang, Xiaoxue; Zhang, Jie; Huang, Qingyu; Liu, Liangpo; Shen, Heqing

    2018-03-01

    The neurotoxicity of arsenic is a serious health problem, especially for children. DNA epigenetic change may be an important pathogenic mechanism, but the molecular pathway remains obscure. In this study, the weaned male Sprague-Dawly (SD) rats were treated with arsenic trioxide via drinking water for 6 months, simulating real developmental exposure situation of children. Arsenic exposure impaired the cognitive abilities, and altered the expression of neuronal activity-regulated genes. Total arsenic concentrations of cortex and hippocampus tissues were significantly increased in a dose-dependent manner. The reduction in 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5hmC) levels as well as the down-regulation of DNA methyltransferases (DNMTs) and ten-eleven translocations (TETs) expression suggested that DNA methylation/demethylation processes were significantly suppressed in brain tissues. S-adenosylmethionine (SAM) level wasn't changed, but the expression of the important indicators of oxidative/anti-oxidative balance and tricarboxylic acid (TCA) cycle was significantly deregulated. Overall, arsenic can disrupt oxidative/anti-oxidative balance, further inhibit TETs expression through TCA cycle and alpha-ketoglutarate (α-KG) pathway, and consequently cause DNA methylation/demethylation disruption. The present study implies oxidative stress but not SAM depletion may lead to DNA epigenetic alteration and arsenic neurotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  9. The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem.

    Science.gov (United States)

    Naujokas, Marisa F; Anderson, Beth; Ahsan, Habibul; Aposhian, H Vasken; Graziano, Joseph H; Thompson, Claudia; Suk, William A

    2013-03-01

    Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons. We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life. We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications. Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U.S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 µg/L; however, concentrations of > 3,000 µg/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood. These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure.

  10. Protective Effect of Psidium guajava in Arsenic-induced Oxidative Stress and Cytological Damage in Rats

    Science.gov (United States)

    Tandon, Neeraj; Roy, Manju; Roy, Sushovan; Gupta, Neelu

    2012-01-01

    This study was undertaken to evaluate the protective effect of aqueous extract of Psidium guajava leaves against sodium arsenite-induced toxicity in experimental rats. Animals were divided into four groups. Control group received arsenic free distilled water and three treatment groups (II, III, and IV) exposed to the arsenic (NaAsO2) (20 mg/kg b.wt) through drinking water. Group III and IV were administered a daily oral dose of P. guajava leaf extract 50 and 100 mg/kg b.wt. (AEPG50 and AEPG100) for the period of 6 weeks. Blood samples and organs were collected at the end of the experiment. Arsenic exposure resulted in significant rise in lipid peroxidation (LPO) levels in erythrocyte, liver, kidney, and brain. In addition toxin decreased (Pguajava) @100 mg/kg body weight) significantly restored activities of oxidative stress markers like LPO levels, GSH levels, SOD, and CAT activities but having the limited protective activity of the herbal extract was observed on tissues architecture. It is therefore concluded that prophylactic co-administration of AEPG could provide specific protection from oxidative injury and to some extent on tissue damage. PMID:23293461

  11. (--Epigallocatechin-3-Gallate Inhibits Arsenic-Induced Inflammation and Apoptosis through Suppression of Oxidative Stress in Mice

    Directory of Open Access Journals (Sweden)

    Nan-Hui Yu

    2017-04-01

    Full Text Available Background/Aims: Exposure to arsenic in individuals has been found to be associated with various health-related problems including skin lesions, cancer, and cardiovascular and immunological disorders. (--Epigallocatechin-3-gallate (EGCG, the main and active polyphenolic catechin present in green tea, has shown potent antioxidant, anti-apoptotic and anti-inflammatory activity in vivo and in vitro. Thus, the present study was conducted to investigate the protective effects of EGCG against arsenic-induced inflammation and immunotoxicity in mice. Methods: Serum IL-1β, IL-6 and TNF-α were determined by ELISA, tissue catalase (CAT, malonyldialdehyde (MDA, superoxide dismutase (SOD, glutathione (GSH, nitric oxide and caspase 3 by commercial kits, mitochondrial membrane potential with Rh 123, mitochondrial ROS with 2’,7’-dichlorofluorescin diacetate (DCFH-DA, apoptotic and necrotic cells and T-cell phenotyping with Flow cytometry analysis. Results: The results showed that arsenic treatment significantly increased oxidative stress levels (as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione and reactive oxygen species, increased levels of inflammatory cytokines and promoted apoptosis. Arsenic exposure increased the relative frequency of the CD8+(Tc cell subpopulation (from 2.8 to 18.9% and decreased the frequency of CD4+(Th cells (from 5.2 to 2.7%. Arsenic exposure also significantly decreased the frequency of T(CD3 (from 32.5% to 19.2% and B(CD19 cells (from 55.1 to 32.5%. All of these effects induced by NaAsO2 were attenuated by EGCG. Conclusions: The present in vitro findings indicate that EGCG attenuates not only NaAsO2-induced immunosuppression but also inflammation and apoptosis.

  12. Influence of prenatal arsenic exposure and newborn sex on global methylation of cord blood DNA.

    Directory of Open Access Journals (Sweden)

    J Richard Pilsner

    Full Text Available BACKGROUND: An emerging body of evidence indicates that early-life arsenic (As exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown. OBJECTIVE: The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh. DESIGN: Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs, maternal blood As (mbAs and cord blood As (cbAs. Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA. RESULTS: In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1 and Q2 vs. Q4; p = 0.06 and 0.04, respectively. Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58 but negative among female newborns (N = 43; tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively and for the association between maternal uAs and LINE-1 (p = 0.07. Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p<0.05. CONCLUSIONS: These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm

  13. Health burden of skin lesions at low arsenic exposure through groundwater in Pakistan. Is river the source?

    International Nuclear Information System (INIS)

    Fatmi, Zafar; Azam, Iqbal; Ahmed, Faiza; Kazi, Ambreen; Gill, Albert Bruce; Kadir, Muhmmad Masood; Ahmed, Mubashir; Ara, Naseem; Janjua, Naveed Zafar

    2009-01-01

    A significant proportion of groundwater in south Asia is contaminated with arsenic. Pakistan has low levels of arsenic in groundwater compared with China, Bangladesh and India. A representative multi-stage cluster survey conducted among 3874 persons ≥15 years of age to determine the prevalence of arsenic skin lesions, its relation with arsenic levels and cumulative arsenic dose in drinking water in a rural district (population: 1.82 million) in Pakistan. Spot-urine arsenic levels were compared among individuals with and without arsenic skin lesions. In addition, the relation of age, body mass index, smoking status with arsenic skin lesions was determined. The geographical distribution of the skin lesions and arsenic-contaminated wells in the district were ascertained using global positioning system. The total arsenic, inorganic and organic forms, in water and spot-urine samples were determined by atomic absorption spectrophotometry. The prevalence of skin lesions of arsenic was estimated for complex survey design, using surveyfreq and surveylogistic options of SAS 9.1 software.The prevalence of definitive cases i.e. hyperkeratosis of both palms and soles, was 3.4 per 1000 and suspected cases i.e. any sign of arsenic skin lesions (melanosis and/or keratosis), were 13.0 per 1000 among ≥15-year-old persons in the district. Cumulative arsenic exposure (dose) was calculated from levels of arsenic in water and duration of use of current drinking water source. Prevalence of skin lesions increases with cumulative arsenic exposure (dose) in drinking water and arsenic levels in urine. Skin lesions were 2.5-fold among individuals with BMI 2 . Geographically, more arsenic-contaminated wells and skin lesions were alongside Indus River, suggests a strong link between arsenic contamination of groundwater with proximity to river.This is the first reported epidemiological and clinical evidence of arsenic skin lesions due to groundwater in Pakistan. Further investigations and

  14. Health burden of skin lesions at low arsenic exposure through groundwater in Pakistan. Is river the source?

    Energy Technology Data Exchange (ETDEWEB)

    Fatmi, Zafar, E-mail: zafar.fatmi@aku.edu [Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi (Pakistan); Azam, Iqbal; Ahmed, Faiza; Kazi, Ambreen; Gill, Albert Bruce; Kadir, Muhmmad Masood; Ahmed, Mubashir; Ara, Naseem; Janjua, Naveed Zafar [Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi (Pakistan)

    2009-07-15

    A significant proportion of groundwater in south Asia is contaminated with arsenic. Pakistan has low levels of arsenic in groundwater compared with China, Bangladesh and India. A representative multi-stage cluster survey conducted among 3874 persons {>=}15 years of age to determine the prevalence of arsenic skin lesions, its relation with arsenic levels and cumulative arsenic dose in drinking water in a rural district (population: 1.82 million) in Pakistan. Spot-urine arsenic levels were compared among individuals with and without arsenic skin lesions. In addition, the relation of age, body mass index, smoking status with arsenic skin lesions was determined. The geographical distribution of the skin lesions and arsenic-contaminated wells in the district were ascertained using global positioning system. The total arsenic, inorganic and organic forms, in water and spot-urine samples were determined by atomic absorption spectrophotometry. The prevalence of skin lesions of arsenic was estimated for complex survey design, using surveyfreq and surveylogistic options of SAS 9.1 software.The prevalence of definitive cases i.e. hyperkeratosis of both palms and soles, was 3.4 per 1000 and suspected cases i.e. any sign of arsenic skin lesions (melanosis and/or keratosis), were 13.0 per 1000 among {>=}15-year-old persons in the district. Cumulative arsenic exposure (dose) was calculated from levels of arsenic in water and duration of use of current drinking water source. Prevalence of skin lesions increases with cumulative arsenic exposure (dose) in drinking water and arsenic levels in urine. Skin lesions were 2.5-fold among individuals with BMI <18.5 kg/m{sup 2}. Geographically, more arsenic-contaminated wells and skin lesions were alongside Indus River, suggests a strong link between arsenic contamination of groundwater with proximity to river.This is the first reported epidemiological and clinical evidence of arsenic skin lesions due to groundwater in Pakistan. Further

  15. Health burden of skin lesions at low arsenic exposure through groundwater in Pakistan. Is river the source?

    Science.gov (United States)

    Fatmi, Zafar; Azam, Iqbal; Ahmed, Faiza; Kazi, Ambreen; Gill, Albert Bruce; Kadir, Muhmmad Masood; Ahmed, Mubashir; Ara, Naseem; Janjua, Naveed Zafar

    2009-07-01

    A significant proportion of groundwater in south Asia is contaminated with arsenic. Pakistan has low levels of arsenic in groundwater compared with China, Bangladesh and India. A representative multi-stage cluster survey conducted among 3874 persons > or = 15 years of age to determine the prevalence of arsenic skin lesions, its relation with arsenic levels and cumulative arsenic dose in drinking water in a rural district (population: 1.82 million) in Pakistan. Spot-urine arsenic levels were compared among individuals with and without arsenic skin lesions. In addition, the relation of age, body mass index, smoking status with arsenic skin lesions was determined. The geographical distribution of the skin lesions and arsenic-contaminated wells in the district were ascertained using global positioning system. The total arsenic, inorganic and organic forms, in water and spot-urine samples were determined by atomic absorption spectrophotometry. The prevalence of skin lesions of arsenic was estimated for complex survey design, using surveyfreq and surveylogistic options of SAS 9.1 software.The prevalence of definitive cases i.e. hyperkeratosis of both palms and soles, was 3.4 per 1000 and suspected cases i.e. any sign of arsenic skin lesions (melanosis and/or keratosis), were 13.0 per 1000 among > or = 15-year-old persons in the district. Cumulative arsenic exposure (dose) was calculated from levels of arsenic in water and duration of use of current drinking water source. Prevalence of skin lesions increases with cumulative arsenic exposure (dose) in drinking water and arsenic levels in urine. Skin lesions were 2.5-fold among individuals with BMI <18.5 kg/m2. Geographically, more arsenic-contaminated wells and skin lesions were alongside Indus River, suggests a strong link between arsenic contamination of groundwater with proximity to river.This is the first reported epidemiological and clinical evidence of arsenic skin lesions due to groundwater in Pakistan. Further

  16. Exposure and bioavailability of arsenic in contaminated soils from the La Parrilla mine, Spain

    Science.gov (United States)

    Anawar, H. M.; Garcia-Sanchez, A.; Murciego, A.; Buyolo, T.

    2006-05-01

    Arsenic derived from mining activity may contaminate water, soil and plant ecosystems resulting in human health and ecotoxicological risks. In this study, exposure assessment of arsenic (As) in soil, spoil, pondwater and plants collected from the areas contaminated by mine tailings and spoils in and around the La Parrilla mine, Caceres province, Spain, was carried out using AAS method. Water solubility, bioavailability and soil-plant transfer coefficients of As and phytoremediation potential of plants were determined. Arsenic concentrations varied from 148 to 2,540 mg/kg in soils of site 1 and from 610 to 1,285 mg/kg in site 2 exceeding the guideline limit for agricultural soil (50 mg/kg). Arsenic concentrations in pond waters varied from 8.8 to 101.4 μg/l. High concentrations of water-soluble As in the soils that ranged from 0.10 to 4.71 mg/kg in site 1 and from 0.46 to 4.75 mg/kg in site 2 exceeded the maximum permitted level of water-soluble As (0.04 mg/kg) in agricultural soils. Arsenic concentrations varied from 0.8 to 149.5 mg/kg dry wt in the plants of site 1 and from 2.0 to 10.0 mg/kg in the plants of site 2. Arsenic concentrations in plants increased in the approximate order: Retama sphaerocarpa phytoremediation of As contaminated soils.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  18. Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.

    Science.gov (United States)

    Zhang, Yang; Duan, Xiaoxu; Li, Jinlong; Zhao, Shuo; Li, Wei; Zhao, Lu; Li, Wei; Nie, Huifang; Sun, Guifang; Li, Bing

    2016-08-01

    Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid.

  19. Review of arsenic contamination and human exposure through water food in rural areas in Vietnam

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, Celia

    2016-05-01

    The Red River Delta in Vietnam is one of the regions whose quaternary aquifers are polluted by arsenic. Chronic toxification by arsenic can cause severe illnesses such as cancer, skin lesions, developmental defects, cardiovascular and neurological diseases, and diabetes. In this study, a food processing craft village in the Red River Delta was investigated regarding the potential risk faced by the population due to arsenic. The potential sources of arsenic are the groundwater, the crops grown in the surroundings, and animal products from local husbandry. However, the occurrence of arsenic in nature is variable, and its bioavailability and toxicity depend very much on its specification: trivalent compounds are more toxic and often more mobile than pentavalent compounds, while inorganic species are generally more toxic than organic ones. Local conditions, such as the redox potential, strongly influence its specification and thus potential bioavailability. The introduction to this work elucidates the key factors which potentially cause human exposure to arsenic: the geological setting of the study area, land and water use patterns, and the current state of research regarding the mobilization, bioavailability and plant uptake of arsenic. Although the study area is located in a region where the groundwater is known to be moderately contaminated by arsenic, the level of arsenic in the groundwater in the village had not previously been determined. In this study, water use in the village was examined by a survey among the farmers and by water analyses, which are presented in the following chapters. Four main water sources (rain, river, tube well and a public municipal waterworks) are used for the different daily activities; the highest risk to human health was found to be the bore well water, which is pumped from the shallow Holocene aquifer. The water from the bore wells is commonly used for cleaning and washing as well as to feed the animals and for food processing

  20. Review of arsenic contamination and human exposure through water food in rural areas in Vietnam

    International Nuclear Information System (INIS)

    Hahn, Celia

    2016-01-01

    The Red River Delta in Vietnam is one of the regions whose quaternary aquifers are polluted by arsenic. Chronic toxification by arsenic can cause severe illnesses such as cancer, skin lesions, developmental defects, cardiovascular and neurological diseases, and diabetes. In this study, a food processing craft village in the Red River Delta was investigated regarding the potential risk faced by the population due to arsenic. The potential sources of arsenic are the groundwater, the crops grown in the surroundings, and animal products from local husbandry. However, the occurrence of arsenic in nature is variable, and its bioavailability and toxicity depend very much on its specification: trivalent compounds are more toxic and often more mobile than pentavalent compounds, while inorganic species are generally more toxic than organic ones. Local conditions, such as the redox potential, strongly influence its specification and thus potential bioavailability. The introduction to this work elucidates the key factors which potentially cause human exposure to arsenic: the geological setting of the study area, land and water use patterns, and the current state of research regarding the mobilization, bioavailability and plant uptake of arsenic. Although the study area is located in a region where the groundwater is known to be moderately contaminated by arsenic, the level of arsenic in the groundwater in the village had not previously been determined. In this study, water use in the village was examined by a survey among the farmers and by water analyses, which are presented in the following chapters. Four main water sources (rain, river, tube well and a public municipal waterworks) are used for the different daily activities; the highest risk to human health was found to be the bore well water, which is pumped from the shallow Holocene aquifer. The water from the bore wells is commonly used for cleaning and washing as well as to feed the animals and for food processing

  1. Maternal exposure to arsenic, cadmium, lead, and mercury and neural tube defects in offspring

    International Nuclear Information System (INIS)

    Brender, Jean D.; Suarez, Lucina; Felkner, Marilyn; Gilani, Zunera; Stinchcomb, David; Moody, Karen; Henry, Judy; Hendricks, Katherine

    2006-01-01

    Arsenic, cadmium, lead, and mercury are neurotoxins, and some studies suggest that these elements might also be teratogens. Using a case-control study design, we investigated the relation between exposure to these heavy metals and neural tube defects (NTDs) in offspring of Mexican-American women living in 1 of the 14 Texas counties bordering Mexico. A total of 184 case-women with NTD-affected pregnancies and 225 control-women with normal live births were interviewed about their environmental and occupational exposures during the periconceptional period. Biologic samples for blood lead and urinary arsenic, cadmium, and mercury were also obtained for a subset of these women. Overall, the median levels of these biomarkers for heavy metal exposure did not differ significantly (P>0.05) between case- and control-women. However, among women in the highest income group, case-women were nine times more likely (95% confidence interval (CI) 1.4-57) than control-women to have a urinary mercury >=5.62μg/L. Case-women were 4.2 times more likely (95% CI 1.1-16) to report burning treated wood during the periconceptional period than control-women. Elevated odds ratios (ORs) were observed for maternal and paternal occupational exposures to arsenic and mercury, but the 95% CIs were consistent with unity. The 95% CIs of the ORs were also consistent with unity for higher levels of arsenic, cadmium, lead, and mercury in drinking water and among women who lived within 2 miles at the time of conception to industrial facilities with reported emissions of any of these heavy metals. Our findings suggest that maternal exposures to arsenic, cadmium, or lead are probably not significant risk factors for NTDs in offspring. However, the elevated urinary mercury levels found in this population and exposures to the combustion of treated wood may warrant further investigation

  2. LACK OF DNA SINGLE STRAND BREAKS IN A LUNG EPITHELIAL CELL LINE AFTER EXPOSURE TO ARSENIC

    Science.gov (United States)

    Arsenic (As) is a carcinogen whose most important target organs include the skin and lungs. Exposure can occur via water ingestion, or inhalation, as As is a by-product of fossil fuel combustion and other industrial activities. The carcinogenic mechanism of action for As remains ...

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ameer, Syeda Shegufta [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Engström, Karin [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden); Hossain, Mohammad Bakhtiar [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Concha, Gabriela [Science Department, Risk Benefit Assessment Unit, National Food Agency, Uppsala (Sweden); Vahter, Marie [Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden); Broberg, Karin, E-mail: Karin.broberg@ki.se [Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden)

    2017-04-15

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

  5. Arsenic-induced dose-dependent modulation of the NF-κB/IL-6 axis in thymocytes triggers differential immune responses

    International Nuclear Information System (INIS)

    Choudhury, Sreetama; Gupta, Payal; Ghosh, Sayan; Mukherjee, Sudeshna; Chakraborty, Priyanka; Chatterji, Urmi; Chattopadhyay, Sreya

    2016-01-01

    Highlights: • We for the first time explicitly show that arsenic exposure causes morphological damage to the thymus and results in heightened death of thymocytes. • Our data suggests that arsenic-induced apoptosis occurs due to increase in cellular oxidative and nitrosative stress. • We have for the first time established a non-classical role of NF-κB, correlating it with increase in FoxP3 expression. • The % of CD4+ CD25+ T cells were high and expression of FoxP3 has also increased at higher doses of arsenic indicating an nTreg bias. - Abstract: Arsenic contamination of drinking water is a matter of global concern. Arsenic intake impairs immune responses and leads to a variety of pathological conditions including cancer. In order to understand the intricate tuning of immune responses elicited by chronic exposure to arsenic, a mouse model was established by subjecting mice to different environmentally relevant concentrations of arsenic in drinking water for 30 days. Detailed study of the thymus, a primary immune organ, revealed arsenic-mediated tissue damage in both histological specimens and scanning electron micrographs. Analysis of molecular markers of apoptosis by Western blot revealed a dose-dependent activation of the apoptotic cascade. Enzymatic assays supported oxidative stress as an instigator of cell death. Interestingly, assessment of inflammatory responses revealed disparity in the NF-κB/IL-6/STAT3 axis, where it was found that in animals consuming higher amounts of arsenic NF-κB activation did not lead to the classical IL-6 upregulation response. This deviation from the canonical pathway was accompanied with a significant rise in numbers of CD4+ CD25+ FoxP3 expressing cells in the thymus. The cytokine profile of the animals exposed to higher doses of arsenic also indicated an immune-suppressed milieu, thus validating that arsenic shapes the immune environment in context to its dose of exposure and that at higher doses it leads to immune

  6. Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Debabrata [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Datta, Soma [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Bhattacharya, Shelley [Environmental Toxicology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Mazumder, Shibnath [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India)]. E-mail: shibnath1@yahoo.co.in

    2007-02-15

    The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 {mu}M) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of 'IL-4 like factors' from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge.

  7. Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

    International Nuclear Information System (INIS)

    Ghosh, Debabrata; Datta, Soma; Bhattacharya, Shelley; Mazumder, Shibnath

    2007-01-01

    The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 μM) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of 'IL-4 like factors' from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge

  8. Urinary Arsenic Metabolites of Subjects Exposed to Elevated Arsenic Present in Coal in Shaanxi Province, China

    Directory of Open Access Journals (Sweden)

    Linsheng Yang

    2011-06-01

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

  9. Atorvastatin acts synergistically with N-acetyl cysteine to provide therapeutic advantage against Fas-activated erythrocyte apoptosis during chronic arsenic exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Debabrata; Sen, Gargi; Sarkar, Avik; Biswas, Tuli

    2011-01-01

    Arsenic is an environmental toxicant that reduces the lifespan of circulating erythrocytes during chronic exposure. Our previous studies had indicated involvement of hypercholesterolemia and reactive oxygen species (ROS) in arsenic-induced apoptotic death of erythrocytes. In this study, we have shown an effective recovery from arsenic-induced death signaling in erythrocytes in response to treatment with atorvastatin (ATV) and N-acetyl cysteine (NAC) in rats. Our results emphasized on the importance of cholesterol in the promotion of ROS-mediated Fas signaling in red cells. Arsenic-induced activation of caspase 3 was associated with phosphatidylserine exposure on the cell surface and microvesiculation of erythrocyte membrane. Administration of NAC in combination with ATV, proved to be more effective than either of the drugs alone towards the rectification of arsenic-mediated disorganization of membrane structural integrity, and this could be linked with decreased ROS accumulation through reduced glutathione (GSH) repletion along with cholesterol depletion. Moreover, activation of caspase 3 was capable of promoting aggregation of band 3 with subsequent binding of autologous IgG and opsonization by C3b that led to phagocytosis of the exposed cells by the macrophages. NAC-ATV treatment successfully amended these events and restored lifespan of erythrocytes from the exposed animals almost to the control level. This work helped us to identify intracellular membrane cholesterol enrichment and GSH depletion as the key regulatory points in arsenic-mediated erythrocyte destruction and suggested a therapeutic strategy against Fas-activated cell death related to enhanced cholesterol and accumulation of ROS.

  10. High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

    Energy Technology Data Exchange (ETDEWEB)

    Steinmaus, Craig, E-mail: craigs@berkeley.edu [Arsenic Health Effects Research Program, UC Berkeley School of Public Health, Berkeley, CA (United States); Ferreccio, Catterina; Acevedo, Johanna [School of Medicine, Pontificia Universidad Católica de Chile, Santiago (Chile); Advanced Center for Chronic Diseases (ACCDiS), FONDAP, Santiago (Chile); Balmes, John R [Arsenic Health Effects Research Program, UC Berkeley School of Public Health, Berkeley, CA (United States); Department of Medicine, University of California, San Francisco, San Francisco, CA (United States); Liaw, Jane [Arsenic Health Effects Research Program, UC Berkeley School of Public Health, Berkeley, CA (United States); Troncoso, Patricia [Laboratorio de Anatomía Patológica Dra. Patricia Troncoso, Iquique (Chile); Hospital Felix Bulnes, Departmento de Anatomía Patológica, Santiago (Chile); Dauphiné, David C [Arsenic Health Effects Research Program, UC Berkeley School of Public Health, Berkeley, CA (United States); Nardone, Anthony [Global Health Sciences Program, University of California, San Francisco, San Francisco, CA (United States); Smith, Allan H [Arsenic Health Effects Research Program, UC Berkeley School of Public Health, Berkeley, CA (United States)

    2016-12-15

    Background: Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods: We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤ 10 μg/L. Results: Compared to adults never exposed > 10 μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 mL decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 mL). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions: Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. - Highlights: • Based on its unique geology, lifetime arsenic exposure can be assessed in north Chile. • Signs and symptoms of lung disease were associated with early-life arsenic exposure. • Evidence of lung disease was also associated with moderate arsenic exposure.

  11. Arsenic and ultraviolet radiation exposure: melanoma in a New Mexico non-Hispanic white population.

    Science.gov (United States)

    Yager, Janice W; Erdei, Esther; Myers, Orrin; Siegel, Malcolm; Berwick, Marianne

    2016-06-01

    Cases of cutaneous melanoma and controls were enrolled in a New Mexico population-based study; subjects were administered questionnaires concerning ultraviolet (UV) and inorganic arsenic (iAs) exposure. Historical iAs exposure was estimated. UV exposure estimates were also derived using geospatial methods. Drinking water samples were collected for iAs analysis. Blood samples were collected for DNA repair (Comet) and DNA repair gene polymorphism assays. Arsenic concentrations were determined in urine and toenail samples. UV exposures during the previous 90 days did not vary significantly between cases and controls. Mean (±SD) current home iAs drinking water was not significantly different for cases and controls [3.98 μg/L (±3.67) vs. 3.47 μg/L (±2.40)]. iAs exposure showed no effect on DNA repair or association with melanoma. Results did not corroborate a previously reported association between toenail As and melanoma risk. Arsenic biomarkers in urine and toenail were highly significantly correlated with iAs in drinking water. A UV-DNA repair interaction for UV exposure over the previous 7-90 days was shown; cases had higher DNA damage than controls at low UV values. This novel finding suggests that melanoma cases may be more sensitive to low-level UV exposure than are controls. A UV-APEX1 interaction was shown. Subjects with the homozygous rare APEX1 DNA repair gene allele had a higher risk of early melanoma diagnosis at low UV exposure compared with those with the homozygous wild type or the heterozygote. Notably, a UV-arsenic interaction on inhibition of DNA repair was not observed at iAs drinking water concentrations below 10 ppb (μg/L).

  12. Association of Low-Moderate Arsenic Exposure and Arsenic Metabolism with Incident Diabetes and Insulin Resistance in the Strong Heart Family Study.

    Science.gov (United States)

    Grau-Perez, Maria; Kuo, Chin-Chi; Gribble, Matthew O; Balakrishnan, Poojitha; Jones Spratlen, Miranda; Vaidya, Dhananjay; Francesconi, Kevin A; Goessler, Walter; Guallar, Eliseo; Silbergeld, Ellen K; Umans, Jason G; Best, Lyle G; Lee, Elisa T; Howard, Barbara V; Cole, Shelley A; Navas-Acien, Ana

    2017-12-20

    High arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity. We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance. We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations (ΣAs). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up. Median ΣAs, iAs%, MMA%, and DMA% was 4.4 μg/g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in ΣAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. ΣAs was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics variants. Among participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and AS3MT variants on diabetes risk. https://doi.org/10.1289/EHP2566.

  13. In Utero Exposure to Arsenic Alters Lung Development and Genes Related to Immune and Mucociliary Function in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Bosco, Anthony; McKenna, Katherine L.; Carter, Kim W.; Elliot, John G.; Berry, Luke J.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2012-01-01

    Background: Exposure to arsenic via drinking water is a global environmental health problem. In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in early adulthood. Objectives: We aimed to investigate how arsenic exposure in early life alters lung development and pathways involved in innate immunity. Methods: Pregnant BALB/c, C57BL/6, and C3H/HeARC mice were exposed to 0 (control) or 100 ?g/L...

  14. Sex-Dependent Effects of the Histone Deacetylase Inhibitor, Sodium Valproate, on Reversal Learning After Developmental Arsenic Exposure

    Directory of Open Access Journals (Sweden)

    Christina R. Steadman Tyler

    2018-06-01

    Full Text Available Several studies have demonstrated that exposure to arsenic in drinking water adversely affects brain development and cognitive function in adulthood. While the mechanism by which arsenic induces adverse neurological outcomes remains elusive, studies suggest a link between reduced levels of histone acetylation and impaired performance on a variety of behavioral tasks following arsenic exposure. Using our developmental arsenic exposure (DAE paradigm, we have previously reported reduced histone acetylation and associated histone acetyltransferase enzyme expression in the frontal cortex of C57BL/6J adult male mice, with no changes observed in the female frontal cortex. In the present study, we sought to determine if DAE produced sex-dependent deficits in frontal cortical executive function using the Y-maze acquisition and reversal learning tasks, which are specific for assessing cognitive flexibility. Further, we tested whether the administration of valproic acid, a class I–IIa histone deacetylase inhibitor, was able to mitigate behavioral and biochemical changes resulting from DAE. As anticipated, DAE inhibited acquisition and reversal learning performance in adult male, but not female, mice. Valproate treatment for 2 weeks restored reversal performance in the male arsenic-exposed offspring, while not affecting female performance. Protein levels of HDACs 1, 2, and 5 were elevated following behavioral assessment but only in DAE male mice; restoration of appropriate HDAC levels occurred after valproate treatment and was concurrent with improved behavioral performance, particularly during reversal learning. Female frontal cortical levels of HDAC enzymes were not impacted by DAE or valproate treatment. Finally, mRNA expression levels of brain-derived neurotrophic factor, Bdnf, which has been implicated in the control of frontal cortical flexibility and is regulated by HDAC5, were elevated in DAE male mice and restored to normal levels following HDACi

  15. Chronic natural arsenic exposure affecting histoarchitecture of gonads in Black Bengal goats (Capra aegagrushircus

    Directory of Open Access Journals (Sweden)

    Md. Abdul Wares

    2015-06-01

    Full Text Available Arsenic is a major water pollutant that may cause serious health hazard (e.g., infertility in human and animal. We evaluated the changes in histoarchitecture of testes and ovaries of adult Black Bengal goats (n=10 reared in arsenic affected areas in Bangladesh. Grossly, we found insignificant variations among the testes and ovaries, but histological evaluation revealed an extensive alteration in morphology of both testes and ovaries in the arsenic affected goats. In testes, the thickening of tunica albugenia and trabeculae, widening of intertubular space between seminiferous tubules, and narrowing in diameter of seminiferous tubules were observed. In ovaries of arsenic affected goats, significant decrease in number of primary follicles and antral follicles were observed. The diameters of secondary and antral follicles were significantly reduced. The granulosa layer of antral follicles showed marked thickening. The findings indicate that chronic arsenic exposure alters the histoarchitecture of both male and female gonads in Black Bengal goat, and thereby may affect their reproductive performance.

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

    Science.gov (United States)

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

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

    International Nuclear Information System (INIS)

    Fillman, Toki; Shimizu-Furusawa, Hana; Ng, Chris Fook Sheng; Parajuli, Rajendra Prasad; Watanabe, Chiho

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Fillman, Toki, E-mail: tokif@humeco.m.u-tokyo.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan); Shimizu-Furusawa, Hana, E-mail: hana-shimizu@umin.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan); Ng, Chris Fook Sheng, E-mail: chrisng-tky@umin.ac.jp [Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki (Japan); Parajuli, Rajendra Prasad, E-mail: rp.parajuli@mcgill.ca [Basu Laboratory, CINE Building, Macdonald Campus, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec (Canada); Watanabe, Chiho, E-mail: chiho@humeco.m.u-tokyo.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan)

    2016-08-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ranft, U.; Miskovic, P.; Pesch, B.; Jakubis, P.; Fabianova, E.; Keegan, T.; Hergemoller, A.; Jakubis, M.; Nieuwenhuijsen, M.J. [University of Dusseldorf, Dusseldorf (Germany)

    2003-06-01

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

  20. The effects of arsenic or the combination of arsenic and radiation exposure is enhanced through the overexpression of the GSTO family member p28

    International Nuclear Information System (INIS)

    Giri, U.; Story, M.D.; Terry, N.H.A.; Giri, D.K.; Calkins, P.R.

    2003-01-01

    Full text: p28 is a member of the GST omega superfamily and has dehydroascorbate reductase, GST, and glutaredoxin activities. Furthermore, p28 is the rate-limiting enzyme in the bio-transformation of arsenic. The monomethyl arsenous reducatase activity of p28 produces dimethylarseniate, the most toxic form of arsenic. We investigated how p28 modulated arsenic cellular sensitivity in two mammalian models: 1) in LY-ar and LY-as cells where p28 is over-expressed and not expressed, respectively; and 2) in stably transfected A549 cells where p28 is over-expressed via a CMV promoter. The LY-ar mouse lymphoma cell line is radio and chemo-resistant and apoptosis refractory, whereas the parental cell line, LY-as, is radiosensitive and apoptotically permissive. In addition, we studied the effect of arsenic as a radiosensitizer in both cell systems. In LY-ar cells arsenic induced a dose- and time- dependent increase in apoptosis, which is comparable to that seen in LY-as cells. Arsenic plus 2.5Gy radiation induced apoptosis in LY-ar cells, which was more than additive. Survival in LY-ar cells was reduced to that of LY-as cells as well as p28 overexpression induced G2/M arrest in A549 cells and the combination of radiation with arsenic decreased the clonogenic survival of both the A549 and A549-p28 cells but the effect is more pronounced in the A549-P28 cell line. A549 and A549-p28 cells did not show a differential response to Taxol, which induces G2/M arrest and cell death via an inhibition of tubulin depolarization. Arsenic modulated the level of reduced GSH in both cell systems in a dose- and time- dependent manner, which correlated with survival outcome. This study illustrated that arsenic acts as a radiosensitizer and p28 augmented the potential of arsenic in inducing apoptosis, G2/M arrest, and radiosensitization. Further studies are underway to examine the bio-chemical pathways involved in arsenic-mediated cell death and the role of p28 therein

  1. Curcumin and turmeric attenuate arsenic-induced angiogenesis in ovo.

    Science.gov (United States)

    Pantazis, Panayotis; Varman, Aarthi; Simpson-Durand, Cindy; Thorpe, Jessica; Ramalingam, Satish; Subramaniam, Dharmalingam; Houchen, Courtney; Ihnat, Michael; Anant, Shrikant; Ramanujam, Rama P

    2010-01-01

    Trivalent arsenic [As(III)] is currently approved by the FDA for the treatment of chronic and acute leukemias. However, As(III) has also demonstrated damaging effects on human health, including development of cardiovascular disease, diabetes, and cancer. Further, As(III) is a potent angiogenic agent. In this context, curcumin, an active ingredient in the dietary agent turmeric, has demonstrated potent antiproliferative, antiinflammatory, and antiangiogenic properties. In this report, we have shown that both curcumin and turmeric inhibit expression of vascular endothelial growth factor in HCT-116 human colon cancer cells exposed to As(III). Further, in the chicken chorioallantoic membrane assay model, treatment with low As(III) concentrations results in extensive increase in blood vessel density, which, however, is reduced in the presence of curcumin or turmeric. Collectively, the findings reported here strongly suggest that turmeric and curcumin can dramatically attenuate the process of angiogenesis induced by low As(III) concentrations.

  2. Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh.

    Science.gov (United States)

    Islam, Rafiqul; Khan, Ismail; Hassan, Sheikh Nazmul; McEvoy, Mark; D'Este, Catherine; Attia, John; Peel, Roseanne; Sultana, Munira; Akter, Shahnaz; Milton, Abul Hasnat

    2012-06-07

    Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 μg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose-response pattern was also observed. These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years.

  3. Association of soil arsenic and nickel exposure with cancer mortality rates, a town-scale ecological study in Suzhou, China.

    Science.gov (United States)

    Chen, Kai; Liao, Qi Lin; Ma, Zong Wei; Jin, Yang; Hua, Ming; Bi, Jun; Huang, Lei

    2015-04-01

    Heavy metals and arsenic are well-known carcinogens. However, few studies have examined whether soil heavy metals and arsenic concentrations associate with cancer in the general population. In this ecological study, we aimed to evaluate the association of heavy metals and arsenic in soil with cancer mortality rates during 2005-2010 in Suzhou, China, after controlling for education and smoking prevalence. In 2005, a total of 1683 soil samples with a sampling density of one sample every 4 km(2) were analyzed. Generalized linear model with a quasi-Poisson regression was applied to evaluate the association between town-scale cancer mortality rates and soil heavy metal concentrations. Results showed that soil arsenic exposure had a significant relationship with colon, gastric, kidney, lung, and nasopharyngeal cancer mortality rates and soil nickel exposure was significantly associated with liver and lung cancer. The associations of soil arsenic and nickel exposure with colon, gastric, kidney, and liver cancer in male were higher than those in female. The observed associations of soil arsenic and nickel with cancer mortality rates were less sensitive to alternative exposure metrics. Our findings would contribute to the understanding of the carcinogenic effect of soil arsenic and nickel exposure in general population.

  4. Persistent Exposure to Arsenic via Drinking Water in Rural Bangladesh Despite Major Mitigation Efforts

    Science.gov (United States)

    Gardner, Renee; Hamadani, Jena; Grandér, Margaretha; Tofail, Fahmida; Nermell, Barbro; Palm, Brita; Kippler, Maria

    2011-01-01

    Objectives. Elevated arsenic levels in tube-well water in Bangladesh have prompted extensive mitigation projects. We evaluated the effectiveness of long-term mitigation efforts by longitudinally measuring arsenic exposure in pregnant women and their children, the most susceptible population groups. Methods. The study was nested in a population-based nutrition intervention in Matlab, Bangladesh. Mother–child pairs (n = 1951) were followed from 2001 to 2003, beginning in early gestation and continuing to 5 years postpartum. We measured arsenic concentrations in urine (U-As) of the 5-year-old children by using high-performance liquid chromatography online with hydride generation and inductively coupled plasma mass spectrometry and compared them with earlier childhood U-As and maternal U-As during pregnancy. Results. Children had elevated U-As at 5 years old (median = 51 μg/L, 5th–95th percentiles = 16–355 μg/L), and U-As distribution was similar to that observed in the mothers during gestation. Children's U-As at 5 years old significantly correlated with their U-As at 1.5 years old and to maternal U-As during early and late gestation. Conclusions. Despite major mitigation efforts, arsenic exposure remains highly elevated in rural Bangladesh. Further mitigation strategies are required and must be rigorously evaluated for long-term efficacy. PMID:21778503

  5. Occupational exposure to chromium, copper and arsenic during work with impregnated wood in joinery shops.

    Science.gov (United States)

    Nygren, O; Nilsson, C A; Lindahl, R

    1992-10-01

    CCA-impregnated timber contains copper, chromium and arsenic (CCA), and occupational exposure to wood dust as well as the CCA compounds may occur in work with such timber. Dust from commercially available impregnated wood has been found to contain hexavalent chromium, which is regarded as a carcinogen. Apart from determinations of the total amounts of the CCA compounds, specific determination of hexavalent chromium is therefore essential. Selective methods have been applied for control of the work environment in six joinery shops. The mean exposure to wood dust was found to be below 1 mg m-3. The mean airborne concentration of arsenic around various types of joinery machines was in the range from 0.54 to 3.1 micrograms m-3. No hexavalent chromium was detected in any samples and no increased concentrations of arsenic were found in urine from the workers. The presence of arsenic in the work-room air must be considered for appropriate assessment of the occupational environment in joinery shops.

  6. Arsenic species in wheat, raw and cooked rice: Exposure and associated health implications.

    Science.gov (United States)

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

    2018-09-01

    Arsenic concentrations above 10μgL -1 were previously found in 89% of ground water sources in six villages of Pakistan. The present study has ascertained the health risks associated with exposure to total arsenic (tAs) and its species in most frequently consumed foods. Inorganic arsenic (iAs) concentrations were found to be 92.5±41.88μgkg -1 , 79.21±76.42μgkg -1 , and 116.38±51.38μgkg -1 for raw rice, cooked rice and wheat respectively. The mean tAs concentrations were 47.47±30.72μgkg -1 , 71.65±74.7μgkg -1 , 105±61.47μgkg -1 . Wheat is therefore demonstrated to be a significant source of arsenic exposure. Dimethylarsinic acid was the main organic species detected in rice, whilst monomethylarsonic acid was only found at trace levels. Total daily intake of iAs exceeded the provisional tolerable daily intake of 2.1μgkg -1 day -1 body weight in 74% of study participants due to concurrent intake from water (94%), wheat (5%) and raw rice (1%). A significant association between tAs in cooked rice and cooking water resulted in tAs intake 43% higher in cooked rice compared to raw rice. The study suggests that arsenic intake from food, particularly from wheat consumption, holds particular significance where iAs is relatively low in water. Chronic health risks were found to be significantly higher from wheat intake than rice, whilst the risk in terms of acute effects was below the USEPA's limit of 1.0. Children were at significantly higher health risk than adults due to iAs exposure from rice and/or wheat. The dietary exposure of participants to tAs was attributable to staple food intake with ground water iAs iAs in drinking water. Although the daily iAs intake from food was lower than total water intake, the potential health risk from exposure to arsenic and its species still exists and requires exposure control measures. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Arsenic exposure and adverse health effects: A review of recent findings from arsenic and health studies in Matlab, Bangladesh

    Directory of Open Access Journals (Sweden)

    Mohammad Yunus

    2011-09-01

    Full Text Available The recent discovery of large-scale arsenic (As contamination of groundwater has raised much concern in Bangladesh. Reliable estimates of the magnitude of As exposure and related health problems have not been comprehensively investigated in Bangladesh. A large population-based study on As and health consequences in Matlab (AsMat was done in Matlab field site where International Centre for Diarrhoeal Disease Research, Bangladesh has maintained a health and demographic surveillance system registering prospectively all vital events. Taking advantage of the health and demographic surveillance system and collecting data on detailed individual level As exposure using water and urine samples, AsMat investigated the morbidity and mortality associated with As exposure. Reviews of findings to date suggest the adverse effects of As exposure on the risk of skin lesions, high blood pressure, diabetes mellitus, chronic disease, and all-cause infant and adult disease mortality. Future studies of clinical endpoints will enhance our knowledge gaps and will give directions for disease prevention and mitigations.

  8. Arsenic exposure and adverse health effects: a review of recent findings from arsenic and health studies in Matlab, Bangladesh.

    Science.gov (United States)

    Yunus, Mohammad; Sohel, Nazmul; Hore, Samar Kumar; Rahman, Mahfuzar

    2011-09-01

    The recent discovery of large-scale arsenic (As) contamination of groundwater has raised much concern in Bangladesh. Reliable estimates of the magnitude of As exposure and related health problems have not been comprehensively investigated in Bangladesh. A large population-based study on As and health consequences in Matlab (AsMat) was done in Matlab field site where International Centre for Diarrhoeal Disease Research, Bangladesh has maintained a health and demographic surveillance system registering prospectively all vital events. Taking advantage of the health and demographic surveillance system and collecting data on detailed individual level As exposure using water and urine samples, AsMat investigated the morbidity and mortality associated with As exposure. Reviews of findings to date suggest the adverse effects of As exposure on the risk of skin lesions, high blood pressure, diabetes mellitus, chronic disease, and all-cause infant and adult disease mortality. Future studies of clinical endpoints will enhance our knowledge gaps and will give directions for disease prevention and mitigations. Copyright © 2011. Published by Elsevier B.V.

  9. Arsenic Speciation in US Consumed Rice with an Emphasis on Bioaccessiblity and the Exposure Assessment Implications Dataset

    Data.gov (United States)

    U.S. Environmental Protection Agency — Arsenic Speciation in US Consumed Rice with an Emphasis on Bioaccessiblity and the Exposure Assessment Implications. This dataset is associated with the following...

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  11. Alpha-lipoic acid protects oxidative stress, changes in cholinergic system and tissue histopathology during co-exposure to arsenic-dichlorvos in rats.

    Science.gov (United States)

    Dwivedi, Nidhi; Flora, Govinder; Kushwaha, Pramod; Flora, Swaran J S

    2014-01-01

    We investigated protective efficacy of α-lipoic acid (LA), an antioxidant against arsenic and DDVP co-exposed rats. Biochemical variables suggestive of oxidative stress, neurological dysfunction, and tissue histopathological alterations were determined. Male rats were exposed either to 50 ppm sodium arsenite in drinking water or in combination with DDVP (4 mg/kg, subcutaneously) for 10 weeks. α-Lipoic acid (50mg/kg, pos) was also co-administered in above groups. Arsenic exposure led to significant oxidative stress along, hepatotoxicity, hematotoxicity and altered brain biogenic amines levels accompanied by increased arsenic accumulation in blood and tissues. These altered biochemical variables were supported by histopathological examinations leading to oxidative stress and cell death. These biochemical alterations were significantly restored by co-administration of α-lipoic acid with arsenic and DDVP alone and concomitantly. The results indicate that arsenic and DDVP induced oxidative stress and cholinergic dysfunction can be significantly protected by the supplementation of α-lipoic acid. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Biological and environmental hazards associated with exposure to chemical warfare agents: arsenicals.

    Science.gov (United States)

    Li, Changzhao; Srivastava, Ritesh K; Athar, Mohammad

    2016-08-01

    Arsenicals are highly reactive inorganic and organic derivatives of arsenic. These chemicals are very toxic and produce both acute and chronic tissue damage. On the basis of these observations, and considering the low cost and simple methods of their bulk syntheses, these agents were thought to be appropriate for chemical warfare. Among these, the best-known agent that was synthesized and weaponized during World War I (WWI) is Lewisite. Exposure to Lewisite causes painful inflammatory and blistering responses in the skin, lung, and eye. These chemicals also manifest systemic tissue injury following their cutaneous exposure. Although largely discontinued after WWI, stockpiles are still known to exist in the former Soviet Union, Germany, Italy, the United States, and Asia. Thus, access by terrorists or accidental exposure could be highly dangerous for humans and the environment. This review summarizes studies that describe the biological, pathophysiological, toxicological, and environmental effects of exposure to arsenicals, with a major focus on cutaneous injury. Studies related to the development of novel molecular pathobiology-based antidotes against these agents are also described. © 2016 New York Academy of Sciences.

  13. Biological and environmental hazards associated with exposure to chemical warfare agents: arsenicals

    Science.gov (United States)

    Li, Changzhao; Srivastava, Ritesh K.; Athar, Mohammad

    2016-01-01

    Arsenicals are highly reactive inorganic and organic derivatives of arsenic. These chemicals are very toxic and produce both acute and chronic tissue damage. Based on these observations, and considering the low cost and simple methods of their bulk syntheses, these agents were thought to be appropriate for chemical warfare. Among these, the most known agent synthesized and weaponized during World War I (WWI) is Lewisite. Exposure to Lewisite causes painful inflammatory and blistering responses in the skin, lung, and eye. These chemicals also manifest systemic tissue injury following their cutaneous exposure. Although largely discontinued after WWI, their stockpiles are still known to exist in the former Soviet Union, Germany, Italy, the United States, and Asia. Thus, their access by terrorists or accidental exposure could be highly dangerous for humans and the environment. This review summarizes studies which describe the biological, pathophysiological, toxicological, and environmental effects of exposure to arsenicals, with a major focus on cutaneous injury. Studies related to the development of novel molecular pathobiology–based antidotes against these agents are also described. PMID:27636894

  14. Ground water pollution by arsenic and its effects on health. Involvement of metabolic methylation in arsenic-induced genetic damage and tumorigenesis; Muki hiso no mechiru ka taisha to idenshi shogaisei narabini shuyo yuhatsusei

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, K. [Nihon Univ., Tokyo (Japan)] Okada, S. [Shizuoka Prefecture (Japan)

    1997-07-10

    Drinking water contamination has become a worldwide problem. It is pointed out that re-evaluation of genetic damage with carcinogen is considered as an important problem particularly arsenic`s effects on health. To explain the genetic damage development mechanism of arsenic compound, results of the research conducted on the action of arsenic compound which develops during metabolic methylation process and inorganic arsenic are explained in this paper. The results of the study are summarized as follows. Arsenic genetic damage mutation is caused by dimethyl arsenic in main metabolism than inorganic arsenic. Lung DNA damage is induced by the interaction of O2 and arsenic peroxide radical. Dimethyl arsenic shows very important effect on lung cancer formation process which is induced based on 4-nitroquinoline-1-oxide (4NQO). It not only promotes lung cancer but it also plays an important role in malignant tumor`s mutation. 25 refs., 2 figs.

  15. Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse.

    Science.gov (United States)

    Pachauri, Vidhu; Flora, Sjs

    2015-01-01

    Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

  16. Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis

    International Nuclear Information System (INIS)

    Chang, Soo Im; Jin, Bohwan; Youn, Pilju; Park, Changbo; Park, Jung-Duck; Ryu, Doug-Young

    2007-01-01

    Oxidative stress has been suggested to be a major cause of male reproductive failure. Here, we investigated whether arsenic, which impairs male reproductive functions in rodent models, acts by inducing oxidative stress. Male 8-week-old ICR mice were given drinking water containing 20 or 40 mg/l sodium arsenite with or without 0.75 or 1.5 g/l of the antioxidant ascorbic acid for 5 weeks. The arsenic-treated mice showed decreased epididymidal sperm counts and testicular weights compared to untreated mice. These effects were reversed in mice that were co-treated with ascorbic acid. Similarly, arsenic treatment lowered the activities of testicular 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD, which play important roles in steroidogenesis, and this was reversed by co-treatment with ascorbic acid. The testicles of arsenic-treated mice had decreased glutathione (GSH) levels (which correlate inversely with the degree of cellular oxidative stress) and elevated levels of protein carbonyl (a marker of oxidative damage to tissue proteins). Ascorbic acid co-treatment reversed both of these effects. Thus, ascorbic acid blocks both the adverse effects of arsenic on male reproductive functions and the arsenic-induced testicular oxidative changes. These observations support the notion that arsenic impairs male reproductive function by inducing oxidative stress

  17. Arsenic and cadmium exposure in children living near a smelter complex in San Luis Potosi, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Barriga, F.; Santos, M.A.; Mejia, J.J.; Batres, L.; Yanez, L.; Carrizales, L.; Vera, E.; del Razo, L.M.; Cebrian, M.E. (Universidad Autonoma de San Luis Potosi (Mexico))

    1993-08-01

    The main purpose of this study was to assess environmental contamination by arsenic and cadmium in a smelter community (San Luis Potosi City, Mexico) and its possible contribution to an increased body burden of these elements in children. Arsenic and cadmium were found in the environment (air, soil, and household dust, and tap water) as well as in the urine and hair from children. The study was undertaken in three zones: Morales, an urban area close to the smelter complex; Graciano, an urban area 7 km away from the complex; and Mexquitic, a small rural town 25 km away. The environmental study showed that Morales is the most contaminated of the zones studied. The range of arsenic levels in soil (117-1396 ppm), dust (515-2625 ppm), and air (0.13-1.45 micrograms/m3) in the exposed area (Morales) was higher than those in the control areas. Cadmium concentrations were also higher in Morales. Estimates of the arsenic ingestion rate in Morales (1.0-19.8 micrograms/kg/day) were equal to or higher than the reference dose of 1 microgram/kg/day calculated by the Environmental Protection Agency. The range of arsenic levels in urine (69-594 micrograms/g creatinine) and hair (1.4-57.3 micrograms/g) and that of cadmium in hair (0.25-3.5 micrograms/g) indicated that environmental exposure has resulted in an increased body burden of these elements in children, suggesting that children living in Morales are at high risk of suffering adverse health effects if exposure continues.

  18. Lung function in adults following in utero and childhood exposure to arsenic in drinking water: preliminary findings.

    Science.gov (United States)

    Dauphiné, David C; Ferreccio, Catterina; Guntur, Sandeep; Yuan, Yan; Hammond, S Katharine; Balmes, John; Smith, Allan H; Steinmaus, Craig

    2011-08-01

    Evidence suggests that arsenic in drinking water causes non-malignant lung disease, but nearly all data concern exposed adults. The desert city of Antofagasta (population 257,976) in northern Chile had high concentrations of arsenic in drinking water (>800 μg/l) from 1958 until 1970, when a new treatment plant was installed. This scenario, with its large population, distinct period of high exposure, and accurate data on past exposure, is virtually unprecedented in environmental epidemiology. We conducted a pilot study on early-life arsenic exposure and long-term lung function. We present these preliminary findings because of the magnitude of the effects observed. We recruited a convenience sample consisting primarily of nursing school employees in Antofagasta and Arica, a city with low drinking water arsenic. Lung function and respiratory symptoms in 32 adults exposed to >800 μg/l arsenic before age 10 were compared to 65 adults without high early-life exposure. Early-life arsenic exposure was associated with 11.5% lower forced expiratory volume in 1 s (FEV(1)) (P = 0.04), 12.2% lower forced vital capacity (FVC) (P = 0.04), and increased breathlessness (prevalence odds ratio = 5.94, 95% confidence interval 1.36-26.0). Exposure-response relationships between early-life arsenic concentration and adult FEV(1) and FVC were also identified (P trend = 0.03). Early-life exposure to arsenic in drinking water may have irreversible respiratory effects of a magnitude similar to smoking throughout adulthood. Given the small study size and non-random recruitment methods, further research is needed to confirm these findings.

  19. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague–Dawley rats

    International Nuclear Information System (INIS)

    Chatterjee, A.; Chatterji, U.

    2011-01-01

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin–eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ERα), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ERα, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: ► Arsenic disrupts the uterine histology and

  20. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  1. Arsenic toxicity induced endothelial dysfunction and dementia: Pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors

    International Nuclear Information System (INIS)

    Sharma, Bhupesh; Sharma, P.M.

    2013-01-01

    Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment of learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good potential in

  2. Arsenic toxicity induced endothelial dysfunction and dementia: Pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Bhupesh, E-mail: drbhupeshresearch@gmail.com; Sharma, P.M.

    2013-11-15

    Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment of learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good potential

  3. Total and inorganic arsenic in dietary supplements based on herbs, other botanicals and algae—a possible contributor to inorganic arsenic exposure

    DEFF Research Database (Denmark)

    Hedegaard, Rikke Susanne Vingborg; Rokkjær, Inge; Sloth, Jens Jørgen

    2013-01-01

    The content of total and inorganic arsenic was determined in 16 dietary supplements based on herbs, other botanicals and algae purchased on the Danish market. The dietary supplements originated from various regions, including Asia, Europe and USA. The contents of total and inorganic arsenic...... was determined by inductively coupled plasma mass spectrometry (ICP-MS) and anion exchange HPLC-ICP-MS, respectively, were in the range of 0.58 to 5.0 mgkg−1 and 0.03 to 3.2 mg kg−1, respectively, with a ratio between inorganic arsenic and total arsenic ranging between 5 and 100 %. Consumption of the recommended...... dose of the individual dietary supplement would lead to an exposure to inorganic arsenic within the range of 0.07 to 13 μg day−1. Such exposure from dietary supplements would in worst case constitute 62.4 % of the range of benchmark dose lower confidence limit values (BMDL01 at 0.3 to 8 μg kg bw−1 kg−1...

  4. In Vivo and In Vitro Arsenic Exposition Induces Oxidative Stress in Anterior Pituitary Gland.

    Science.gov (United States)

    Ronchetti, Sonia A; Bianchi, María S; Duvilanski, Beatriz H; Cabilla, Jimena P

    2016-07-01

    Inorganic arsenic (iAs) is at the top of toxic metalloids. Inorganic arsenic-contaminated water consumption is one of the greatest environmental health threats worldwide. Human iAs exposure has been associated with cancers of several organs, neurological disorders, and reproductive problems. Nevertheless, there are no reports describing how iAs affects the anterior pituitary gland. The aim of this study was to investigate the mechanisms involved in iAs-mediated anterior pituitary toxicity both in vivo and in vitro. We showed that iAs administration (from 5 to 100 ppm) to male rats through drinking water increased messenger RNA expression of several oxidative stress-responsive genes in the anterior pituitary gland. Serum prolactin levels diminished, whereas luteinizing hormone (LH) levels were only affected at the higher dose tested. In anterior pituitary cells in culture, 25 µmol/L iAs significantly decreased prolactin release in a time-dependent fashion, whereas LH levels remained unaltered. Cell viability was significantly reduced mainly by apoptosis evidenced by morphological and phosphatidylserine externalization studies. This process is characterized by early depolarization of mitochondrial membrane potential and increased levels of reactive oxygen species. Expression of some key oxidative stress-responsive genes, such as heme oxygenase-1 and metallothionein-1, was also stimulated by iAs exposure. The antioxidant N-acetyl cysteine prevented iAs-induced effects on the expression of oxidative stress markers, prolactin release, and apoptosis. In summary, the present work demonstrates for the first time that iAs reduces prolactin release both in vivo and in vitro and induces apoptosis in anterior pituitary cells, possibly resulting from imbalanced cellular redox status. © The Author(s) 2016.

  5. Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats.

    Science.gov (United States)

    Yadav, Rajesh S; Shukla, Rajendra K; Sankhwar, Madhu Lata; Patel, Devendra K; Ansari, Reyaz W; Pant, Aditya B; Islam, Fakhrul; Khanna, Vinay K

    2010-09-01

    Our recent studies have shown that arsenic-induced neurobehavioral toxicity is protected by curcumin by modulating oxidative stress and dopaminergic functions in rats. In addition, the neuroprotective effect of curcumin has been investigated on arsenic-induced alterations in biogenic amines, their metabolites and nitric oxide (NO), which play an important role in neurotransmission process. Decrease in the levels of dopamine (DA, 28%), norepinephrine (NE, 54%), epinephrine (EPN, 46%), serotonin (5-HT, 44%), 3,4-dihydroxyphenylacetic acid (DOPAC, 20%) and homovanillic acid (HVA, 31%) in corpus striatum; DA (51%), NE (22%), EPN (47%), 5-HT (25%), DOPAC (34%) and HVA (41%) in frontal cortex and DA (35%), NE (35%), EPN (29%), 5-HT (54%), DOPAC (37%) and HVA (46%) in hippocampus, observed in arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) treated rats exhibited a trend of recovery in rats simultaneously treated with arsenic and curcumin (100 mg/kg body weight, p.o., 28 days). Increased levels of NO in corpus striatum (2.4-fold), frontal cortex (6.1-fold) and hippocampus (6.2-fold) in arsenic-treated rats were found decreased in rats simultaneously treated with arsenic and curcumin. It is evident that curcumin modulates levels of brain biogenic amines and NO in arsenic-exposed rats and these results further strengthen its neuroprotective efficacy. Copyright © 2010 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Tseng, C.-H.

    2009-01-01

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

  7. Non-melanoma skin cancer: occupational risk from UV light and arsenic exposure.

    Science.gov (United States)

    Surdu, Simona

    2014-01-01

    Non-melanoma skin cancer (NMSC) has a significant impact on public health and health care costs as a result of high morbidity and disfigurement due to the destruction of surrounding tissues. Although the mortality rates of these tumors are low, the high incidence rates determine a considerable number of deaths. NMSC is the most common type of skin cancer, representing about 1/3 of all malignancies diagnosed worldwide each year. The most common NMSC are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Studies on humans and experimental animals indicate that ultraviolet (UV) light and arsenic play important roles in the development of these skin malignancies. Several epidemiological studies have investigated the risk of developing NMSC and the potential link between exposure to sunlight and arsenic in the agricultural and industrial occupational settings. To date, the published literature suggests that there is no apparent skin cancer risk as regards workplace exposure to artificial UV light or arsenic. Concerning UV light from sun exposure at the workplace, most published studies indicated an elevated risk for SCC, but are less conclusive for BCC. Many of these studies are limited by the methodology used in the evaluation of occupational exposure and the lack of adjustment for major confounders. Therefore, further epidemiological studies are required to focus on exposure assessment at the individual level as well as potential interactions with other occupational and non-occupational exposures and individual susceptibility. In doing so, we can better quantify the true risk of skin cancer in exposed workers and inform effective public health prevention programs.

  8. Effects of different inorganic arsenic species in Cyprinus carpio (Cyprinidae) tissues after short-time exposure: Bioaccumulation, biotransformation and biological responses

    International Nuclear Information System (INIS)

    Ventura-Lima, Juliane; Fattorini, Daniele; Regoli, Francesco; Monserrat, Jose M.

    2009-01-01

    Differences in the toxicological and metabolic pathway of inorganic arsenic compounds are largely unknown for aquatic species. In the present study the effects of short-time and acute exposure to As III and As V were investigated in gills and liver of the common carp, Cyprinus carpio (Cyprinidae), measuring accumulation and chemical speciation of arsenic, and the activity of glutathione-S-transferase omega (GST Ω), the rate limiting enzyme in biotransformation of inorganic arsenic. Oxidative biomarkers included antioxidant defenses (total glutathione-S-transferases, glutathione reductase, glutathione, and glucose-6-phosphate dehydrogenase), total scavenging capacity toward peroxyl radicals, reactive oxygen species (ROS) measurement and lipid peroxidation products. A marked accumulation of arsenic was observed only in gills of carps exposed to 1000 ppb As V . Also in gills, antioxidant responses were mostly modulated through a significant induction of glucose-6-phosphate dehydrogenase activity which probably contributed to reduce ROS formation; however this increase was not sufficient to prevent lipid peroxidation. No changes in metal content were measured in liver of exposed carps, characterized by lower activity of GST Ω compared to gills. On the other hand, glutathione metabolism was more sensitive in liver tissue, where a significant inhibition of glutathione reductase was concomitant with increased levels of glutathione and higher total antioxidant capacity toward peroxyl radicals, thus preventing lipid peroxidation and ROS production. The overall results of this study indicated that exposure of C. carpio to As III and As V can induce different responses in gills and liver of this aquatic organism. - Common carp (Cyprinus carpio) presented marked differences between gills and liver after arsenic exposure in terms of antioxidant responses and also in biotransformation.

  9. Effects of different inorganic arsenic species in Cyprinus carpio (Cyprinidae) tissues after short-time exposure: Bioaccumulation, biotransformation and biological responses

    Energy Technology Data Exchange (ETDEWEB)

    Ventura-Lima, Juliane [Instituto de Ciencias Biologicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS (Brazil); Programa de Pos-Graduacao em Ciencias Fisiologicas - Fisiologia Animal Comparada (FURG), Rio Grande, RS (Brazil); Fattorini, Daniele; Regoli, Francesco [Istituto di Biologia e Genetica, Universita Politecnica delle Marche, 60100, Ancona (Italy); Monserrat, Jose M., E-mail: josemmonserrat@pesquisador.cnpq.b [Instituto de Ciencias Biologicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS (Brazil); Programa de Pos-Graduacao em Ciencias Fisiologicas - Fisiologia Animal Comparada (FURG), Rio Grande, RS (Brazil)

    2009-12-15

    Differences in the toxicological and metabolic pathway of inorganic arsenic compounds are largely unknown for aquatic species. In the present study the effects of short-time and acute exposure to As{sup III} and As{sup V} were investigated in gills and liver of the common carp, Cyprinus carpio (Cyprinidae), measuring accumulation and chemical speciation of arsenic, and the activity of glutathione-S-transferase omega (GST OMEGA), the rate limiting enzyme in biotransformation of inorganic arsenic. Oxidative biomarkers included antioxidant defenses (total glutathione-S-transferases, glutathione reductase, glutathione, and glucose-6-phosphate dehydrogenase), total scavenging capacity toward peroxyl radicals, reactive oxygen species (ROS) measurement and lipid peroxidation products. A marked accumulation of arsenic was observed only in gills of carps exposed to 1000 ppb As{sup V}. Also in gills, antioxidant responses were mostly modulated through a significant induction of glucose-6-phosphate dehydrogenase activity which probably contributed to reduce ROS formation; however this increase was not sufficient to prevent lipid peroxidation. No changes in metal content were measured in liver of exposed carps, characterized by lower activity of GST OMEGA compared to gills. On the other hand, glutathione metabolism was more sensitive in liver tissue, where a significant inhibition of glutathione reductase was concomitant with increased levels of glutathione and higher total antioxidant capacity toward peroxyl radicals, thus preventing lipid peroxidation and ROS production. The overall results of this study indicated that exposure of C. carpio to As{sup III} and As{sup V} can induce different responses in gills and liver of this aquatic organism. - Common carp (Cyprinus carpio) presented marked differences between gills and liver after arsenic exposure in terms of antioxidant responses and also in biotransformation.

  10. Ameliorative potential of Psidium guajava in induced arsenic toxicity in Wistar rats

    Directory of Open Access Journals (Sweden)

    Manju Roy and Sushovan Roy

    2011-04-01

    Full Text Available The study was undertaken to determine the effect of Psidium.guajava leaf extract on arsenic induced biochemical alterations in Wistar rats. Significant (P<0.05 increased glucose serum urea nitrogen and serum creatinine was observed whereas non significant decrease in total protein, calcium and phosphorus was observed. It is concluded that kidney damage caused by arsenic can be repaired up to some extent by AEPG50. [Veterinary World 2011; 4(2.000: 82-83

  11. Diffuse parenchymal lung disease in a case of chronic arsenic exposure

    Directory of Open Access Journals (Sweden)

    Somnath Bhattacharya

    2016-01-01

    Full Text Available A 42-year-old housewife, the resident of rural part of West Bengal, presented with gradually progressive exertional dyspnea associated with a dry cough for last 3 years clinical features were suggestive of diffuse parenchymal lung disease (DPLD. Her chest X-ray posteroanterior view and high resolution computed tomography scan of the thorax showed bilateral patchy ground glass opacities and reticulonodular pattern. Search for the etiology revealed classical skin findings of chronic arsenic exposure in the form of generalized darkening and thickening of skin and keratotic lesions over the palms and soles and classical raindrop pigmentation over leg which was present for last 7 years subsequently her bronchoalveolar lavage fluid, hair, nail, and drinking water showed significant amount of arsenic contamination. By exclusion of all known causes of DPLD, we concluded that it was a case of DPLD due to chronic arsenic exposure. To the best of our knowledge, only few case report of DPLD in chronic arsenicosis has been reported till date.

  12. Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine

    International Nuclear Information System (INIS)

    Santra, Amal; Chowdhury, Abhijit; Ghatak, Subhadip; Biswas, Ayan; Dhali, Gopal Krishna

    2007-01-01

    Arsenicosis, caused by arsenic contamination of drinking water supplies, is a major public health problem in India and Bangladesh. Chronic liver disease, often with portal hypertension occurs in chronic arsenicosis, contributes to the morbidity and mortality. The early cellular events that initiate liver cell injury due to arsenicosis have not been studied. Our aim was to identify the possible mechanisms related to arsenic-induced liver injury in mice. Liver injury was induced in mice by arsenic treatment. The liver was used for mitochondrial oxidative stress, mitochondrial permeability transition (MPT). Evidence of apoptosis was sought by TUNEL test, caspase assay and histology. Pretreatment with N-acetyl-L-cysteine (NAC) was done to modulate hepatic GSH level. Arsenic treatment in mice caused liver injury associated with increased oxidative stress in liver mitochondria and alteration of MPT. Altered MPT facilitated cytochrome c release in the cytosol, activation of caspase 9 and caspase 3 activities and apoptotic cell death. Pretreatment of NAC to arsenic-treated mice abrogated all these alteration suggesting a glutathione (GSH)-dependent mechanism. Oxidative stress in mitochondria and inappropriate MPT are important in the pathogenesis of arsenic induced apoptotic liver cell injury. The phenomenon is GSH dependent and supplementation of NAC might have beneficial effects

  13. Evaluation of Urinary Arsenic as an Indicator of Exposure to ...

    African Journals Online (AJOL)

    komla

    West African Journal of Applied Ecology, Vol. ... human exposure to As through contaminated groundwater is a serious health threat in many Asian and Latin .... geology. Kuma & Younger (2001) reported that the pH of the soils in the Tarkwa ...

  14. Probabilistic Risk Assessment of Cancer from Exposure Inorganic Arsenic in Duplicate Food by Villagers in Ronphibun, Thailand

    OpenAIRE

    Piyawat Saipan

    2010-01-01

    Ronphibun district is a district in Nakorn Si Thammarat province, within southern Thailand. This district is the site of several former tin mines that were in operation 100 years ago. Arsenic contamination caused by past mining activities remains in the area. The specific purpose of this study was conducted to assess cancer risk in people living within Ronphibun district from exposure to inorganic arsenic via duplicate food using probabilistic risk assessment. A hundred and fifty duplicate fo...

  15. Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid

    Energy Technology Data Exchange (ETDEWEB)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C. [Bose Institute, Department of Chemistry, Kolkata, West Bengal (India)

    2008-03-15

    Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO{sub 2} was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO{sub 2} at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO{sub 2} intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property. (orig.)

  16. Role and mechanism of arsenic in regulating angiogenesis.

    Directory of Open Access Journals (Sweden)

    Ling-Zhi Liu

    Full Text Available Arsenic is a wide spread carcinogen associated with several kinds of cancers including skin, lung, bladder, and liver cancers. Lung is one of the major targets of arsenic exposure. Angiogenesis is the pivotal process during carcinogenesis and chronic pulmonary diseases, but the role and mechanism of arsenic in regulating angiogenesis remain to be elucidated. In this study we show that short time exposure of arsenic induces angiogenesis in both human immortalized lung epithelial cells BEAS-2B and adenocarcinoma cells A549. To study the molecular mechanism of arsenic-inducing angiogenesis, we find that arsenic induces reactive oxygen species (ROS generation, which activates AKT and ERK1/2 signaling pathways and increases the expression of hypoxia-inducible factor 1 (HIF-1 and vascular endothelial growth factor (VEGF. Inhibition of ROS production suppresses angiogenesis by decreasing AKT and ERK activation and HIF-1 expression. Inhibition of ROS, AKT and ERK1/2 signaling pathways is sufficient to attenuate arsenic-inducing angiogenesis. HIF-1 and VEGF are downstream effectors of AKT and ERK1/2 that are required for arsenic-inducing angiogenesis. These results shed light on the mechanism of arsenic in regulating angiogenesis, and are helpful to develop mechanism-based intervention to prevent arsenic-induced carcinogenesis and angiogenesis in the future.

  17. Probabilistic Risk Assessment of Cancer from Exposure Inorganic Arsenic in Duplicate Food by Villagers in Ronphibun, Thailand

    Directory of Open Access Journals (Sweden)

    Piyawat Saipan

    2010-07-01

    Full Text Available Ronphibun district is a district in Nakorn Si Thammarat province, within southern Thailand. This district is the site of several former tin mines that were in operation 100 years ago. Arsenic contamination caused by past mining activities remains in the area. The specific purpose of this study was conducted to assess cancer risk in people living within Ronphibun district from exposure to inorganic arsenic via duplicate food using probabilistic risk assessment. A hundred and fifty duplicate food samples were collected from participants. Inorganic arsenic concentrations are determined by hydride generation atomic absorption spectrometry. Inorganic arsenic concentrations in duplicate food ranged from 0.16 to 0.42 μg/g dry weight. The probabilistic carcinogenic risk levels were 6.76 x 10-4 and 1.74 x 10-3 based on the 50th and 95th percentile, respectively. Risk values for people in Ronphibun from exposure to inorganic arsenic remained higher than the acceptable target risk. Sensitivity analysis indicted that exposure duration and concentrations of arsenic in food were the two most influential of cancer risk estimates.

  18. The Role of Antioxidants in Biochemical Disorders Induced by Arsenic in Adult male Rats

    International Nuclear Information System (INIS)

    Hassanin, M.M.; Zaki, Z.T.; Emarah, E.A.M.; Hussein, A.M.M.

    2010-01-01

    The present investigation included biochemical, radiometric, molecular studies and histopathological examination to evaluate the protective role of Antox tablets toward Arsenic toxicity in adult male albino rats (Rattus rattus). Arsenic were given as sodium arsenate to different groups in drinking water at a dose of 100 mg/L, for 3 and 6 weeks led to severe tissue damage as revealed by an elevation of serum total protein and alteration of serum protein fractions. Using radioimmunoassay it was found that serum total testosterone level was significantly decreased. The decreased level of total testosterone paralleled the observed testicular damage. Treatment of male rats with antioxidant (Antox) along with arsenic led to an improvement in both the biochemical and histological alterations induced by arsenic. Thus the protective role of Antox is attributed to its antioxidant and free radicals scavenging properties of its components (selenium, vitamin A acetate, ascorbic acid and vitamin E).

  19. Combined Administration of Taurine and Monoisoamyl Dmsa Protects Arsenic Induced Oxidative Injury in Rats

    Directory of Open Access Journals (Sweden)

    Swaran J. S. Flora

    2008-01-01

    Full Text Available Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA, administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks were treated with taurine (100 mg/kg, i.p., once daily, monoisoamyl dimercaptosuccinic acid (MiADMSA (50 mg/kg, oral, once daily either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood δ-aminolevulinic acid dehydratase (ALAD activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP level. Clinical hematological variables like white blood cells (WBC, mean cell hemoglobin (MCH, and mean cell hemoglobin concentration (MCHC showed significant decrease with a significant elevation in platelet (PLT count. These changes were accompanied by significant decrease in superoxide dismutase (SOD activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH level and an increase in oxidized glutathione (GSSG. These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co

  20. A comparison of arsenic exposure in young children and home water arsenic in two rural West Texas communities

    Directory of Open Access Journals (Sweden)

    Michelle Del Rio

    2017-10-01

    Full Text Available Abstract Background In a previously conducted Health Impact Assessment of a well-water dependent southwest community, arsenic (As levels greater than the EPA Maximum Contaminant Level (10 μg/L were identified in home water samples. The goals of this study were to test whether children from the previously studied well-water dependent community (Community 1 had higher blood As levels than children from a demographically similar and geographically nearby community dependent on a municipal water supply (Community 2; to test whether home water As levels predicted child As blood levels; and to examine how child As blood levels changed over time. Methods This was an observational study of 252 children aged 4 to 12 years from two communities. Children were recruited through elementary schools and tested during the school day; 204 children participated in follow-up testing. Home water samples were collected according to U.S. Environmental Protection agency recommended procedures. Child heavy metal blood levels and home water sample heavy metal levels were analyzed using inductively coupled plasma mass spectrometry. General linear regression analysis was used to test the influence of community on child As levels, and to examine the contribution of home water As levels to child blood As levels. Results Arsenic was detectable in all children tested. Blood levels ranged from 0.09–2.61 μg/dL; approximately 31% of children tested at Time I (79/252 had blood As values above the current acceptable limit (1.2 μg/dL. Approximately 8% of household water samples (6/76 had As levels higher than 10 μg/L. Community did not predict child blood As levels; seasonal effects differed by Community. At Time II, child blood As levels were higher in Community 2 than in Community 1. Conclusion A large proportion of children in the communities tested had As exposure. Home water As levels did not predict child blood As levels. Fluctuating child blood As levels by season

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

    Energy Technology Data Exchange (ETDEWEB)

    Li, X.; Pi, J.B.; Li, B.; Xu, Y.Y.; Jin, Y.P.; Sun, G.F. [China Medical University, Shenyang (China). Dept. for Occupational & Environmental Health

    2008-10-15

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

  2. Arsenic exposure and outcomes of antimonial treatment in visceral leishmaniasis patients in Bihar, India: a retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    Meghan R Perry

    2015-03-01

    Full Text Available In the late twentieth century, emergence of high rates of treatment failure with antimonial compounds (SSG for visceral leishmaniasis (VL caused a public health crisis in Bihar, India. We hypothesize that exposure to arsenic through drinking contaminated groundwater may be associated with SSG treatment failure due to the development of antimony-resistant parasites.A retrospective cohort design was employed, as antimony treatment is no longer in routine use. The study was performed on patients treated with SSG between 2006 and 2010. Outcomes of treatment were assessed through a field questionnaire and treatment failure used as a proxy for parasite resistance. Arsenic exposure was quantified through analysis of 5 water samples from within and surrounding the patient's home. A logistic regression model was used to evaluate the association between arsenic exposure and treatment failure. In a secondary analysis survival curves and Cox regression models were applied to assess the risk of mortality in VL patients exposed to arsenic.One hundred and ten VL patients treated with SSG were analysed. The failure rate with SSG was 59%. Patients with high mean local arsenic level had a non-statistically significant higher risk of treatment failure (OR = 1.78, 95% CI: 0.7-4.6, p = 0.23 than patients using wells with arsenic concentration <10 μg/L. Twenty one patients died in our cohort, 16 directly as a result of VL. Arsenic levels ≥ 10 μg/L increased the risk of all-cause (HR 3.27; 95% CI: 1.4-8.1 and VL related (HR 2.65; 95% CI: 0.96-7.65 deaths. This was time dependent: 3 months post VL symptom development, elevated risks of all-cause mortality (HR 8.56; 95% CI: 2.5-29.1 and of VL related mortality (HR 9.27; 95% CI: 1.8-49.0 were detected.This study indicates a trend towards increased treatment failure in arsenic exposed patients. The limitations of the retrospective study design may have masked a strong association between arsenic exposure and selection

  3. Arsenic in private well water part 3 of 3: Socioeconomic vulnerability to exposure in Maine and New Jersey.

    Science.gov (United States)

    Flanagan, Sara V; Spayd, Steven E; Procopio, Nicholas A; Marvinney, Robert G; Smith, Andrew E; Chillrud, Steven N; Braman, Stuart; Zheng, Yan

    2016-08-15

    Arsenic is a naturally occurring toxic element often concentrated in groundwater at levels unsafe for human consumption. Private well water in the United States is mostly unregulated by federal and state drinking water standards. It is the responsibility of the over 13 million U.S. households regularly depending on private wells for their water to ensure it is safe for drinking. There is a consistent graded association with health outcomes at all levels of socioeconomic status (SES) in the U.S. Differential exposure to environmental risk may be contributing to this persistent SES-health gradient. Environmental justice advocates cite overwhelming evidence that income and other SES measures are consistently inversely correlated with exposure to suboptimal environmental conditions including pollutants, toxins, and their impacts. Here we use private well household surveys from two states to investigate the association between SES and risks for arsenic exposure, examining the potentially cumulative effects of residential location, testing and treatment behavior, and psychological factors influencing behavior. We find that the distribution of natural arsenic hazard in the environment is socioeconomically random. There is no evidence that higher SES households are avoiding areas with arsenic or that lower SES groups are disproportionately residing in areas with arsenic. Instead, disparities in exposure arise from differing rates of protective action, primarily testing well water for arsenic, and secondly treating or avoiding contaminated water. We observe these SES disparities in behavior as well as in the psychological factors that are most favorable to these behaviors. Assessment of risk should not be limited to the spatial occurrence of arsenic alone. It is important that social vulnerability factors are incorporated into risk modeling and identifying priority areas for intervention, which should include strategies that specifically target socioeconomically vulnerable

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

    Science.gov (United States)

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

    2015-04-24

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

  5. Arsenic (As Contamination in Different Food and Dietary Samples from Several Districts of Bangladesh and Arsenic (As Detection, Mitigation and Toxicity Measurement and impact of Dietary Arsenic Exposure on Human Health

    Directory of Open Access Journals (Sweden)

    M A Awal

    2010-10-01

    Full Text Available Objective: To determine the level of arsenic concentration in vegetables and other food categories in three selected areas of Pabna district and to estimate quantitatively the dietary arsenic exposure in one of the arsenic contaminated areas of Bangladesh.Materials and Methods: The study was conducted in CharRuppur, Char mirkamari and Lakshmikunda village of IshwardiUpzila in Pabna district. Ishwardi (Town consists of 12 wardsand 37 mahallas. Arsenic was detected in the ADM Lab,Department of Pharmacology, Bangladesh Agricultural University, Mymensingh with Hydride Generation Atomic Absorption Spectrophotometer (HG-AAS; PG-990, PG Instruments Ltd. UK. Arsenic was detected by forming AsH3 at below pH 1.0 after the reaction of As with a solution of sodiumborohydride (NaBH4, sodium hydroxide (NaOH, M=40,000g/mol, and 10% HCl. In this test, standard was maintained asAsV ranging from 0 to 12.5 μg/L.Results: A total of 120 vegetable samples, 15 rice samples and15 fish samples were collected from five different markets ofthree different villages of Pabna district and were tested forarsenic concentration. Findings demonstrated that the mean concentration of As in leafy vegetables (0.52 μg g-1 was significantly higher compared to those found in fruity (0.422μg g-1 and root & tuber vegetables (0.486 μg g-1.Conclusion: Underground Contaminated water was the major source for the As contamination of various products in Pabna.The arsenic levels were found higher among the leafy vegetables samples in comparison to fruit and root & tuber vegetables. Further studies will be conducted to search the genetic risk factors of arsenic toxicity in the population of the mostly affected people.

  6. Arsenic levels in wipe samples collected from play structures constructed with CCA-treated wood: Impact on exposure estimates

    Energy Technology Data Exchange (ETDEWEB)

    Barraj, Leila M. [Chemical Regulation and Food Safety, Exponent, Inc., Suite 1100, 1150 Connecticut Ave., NW, Washington, DC 20036 (United States)], E-mail: lbarraj@exponent.com; Scrafford, Carolyn G. [Chemical Regulation and Food Safety, Exponent, Inc., Suite 1100, 1150 Connecticut Ave., NW, Washington, DC 20036 (United States); Eaton, W. Cary [RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709 (United States); Rogers, Robert E.; Jeng, Chwen-Jyh [Toxcon Health Sciences Research Centre Inc., 9607 - 41 Avenue, Edmonton, Alberta, T6E 5X7 (Canada)

    2009-04-01

    Lumber treated with chromated copper arsenate (CCA) has been used in residential outdoor wood structures and playgrounds. The U.S. EPA has conducted a probabilistic assessment of children's exposure to arsenic from CCA-treated structures using the Stochastic Human Exposure and Dose Simulation model for the wood preservative scenario (SHEDS-Wood). The EPA assessment relied on data from an experimental study using adult volunteers and designed to measure arsenic in maximum hand and wipe loadings. Analyses using arsenic handloading data from a study of children playing on CCA-treated play structures in Edmonton, Canada, indicate that the maximum handloading values significantly overestimate the exposure that occurs during actual play. The objective of our paper is to assess whether the dislodgeable arsenic residues from structures in the Edmonton study are comparable to those observed in other studies and whether they support the conclusion that the values derived by EPA using modeled maximum loading values overestimate hand exposures. We compared dislodgeable arsenic residue data from structures in the playgrounds in the Edmonton study to levels observed in studies used in EPA's assessment. Our analysis showed that the dislodgeable arsenic levels in the Edmonton playground structures are similar to those in the studies used by EPA. Hence, the exposure estimates derived using the handloading data from children playing on CCA-treated structures are more representative of children's actual exposures than the overestimates derived by EPA using modeled maximum values. Handloading data from children playing on CCA-treated structures should be used to reduce the uncertainty of modeled estimates derived using the SHEDS-Wood model.

  7. Exiguobacterium mediated arsenic removal and its protective effect against arsenic induced toxicity and oxidative damage in freshwater fish, Channa striata

    Directory of Open Access Journals (Sweden)

    Neha Pandey

    2015-01-01

    Full Text Available Arsenic is a toxic metalloid existing widely in the environment, and its removal from contaminated water has become a global challenge. The use of bacteria in this regard finds a promising solution. In the present study, Exiguobacterium sp. As-9, which is an arsenic resistant bacterium, was selected with respect to its arsenic removal efficiency. Quantification of arsenic in the water treated with bacterium showed that Exiguobacterium efficiently removed up to 99% of arsenic in less than 20 h. In order to reveal the possible effect of this bacterium in removal of arsenic from water and protecting fishes from the detrimental effects of arsenic, we initiated a range of studies on fresh water fish, Channa striata. It was observed that the fishes introduced into bacteria treated water displayed no symptoms of arsenic toxicity which was marked by a decreased oxidative damage, whereas the fishes exposed to arsenic revealed a significant (p < 0.05 increase in the oxidative stress together with the elevated levels of malondialdehyde. Determination of the bioaccumulation of arsenic in the liver tissues of C. striata using hydride generation atomic absorption spectrophotometry (HG-AAS revealed an increased As(III accumulation in the fishes exposed to arsenic whereas the arsenic level in the control and bacteria treated fishes were found below the detectable limit. In conclusion, this study presents the strategies of bacterial arsenic removal with possible directions for future research.

  8. Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice

    International Nuclear Information System (INIS)

    Ghatak, Subhadip; Biswas, Ayan; Dhali, Gopal Krishna; Chowdhury, Abhijit; Boyer, James L.; Santra, Amal

    2011-01-01

    Arsenic is an environmental toxicant and carcinogen. Exposure to arsenic is associated with development of liver fibrosis and portal hypertension through ill defined mechanisms. We evaluated hepatic fibrogenesis after long term arsenic exposure in a murine model. BALB/c mice were exposed to arsenic by daily gavages of 6 μg/gm body weight for 1 year and were evaluated for markers of hepatic oxidative stress and fibrosis, as well as pro-inflammatory, pro-apoptotic and pro-fibrogenic factors at 9 and 12 months. Hepatic NADPH oxidase activity progressively increased in arsenic exposure with concomitant development of hepatic oxidative stress. Hepatic steatosis with occasional collection of mononuclear inflammatory cells and mild portal fibrosis were the predominant liver lesion observed after 9 months of arsenic exposure, while at 12 months, the changes included mild hepatic steatosis, inflammation, necrosis and significant fibrosis in periportal areas. The pathologic changes in the liver were associated with markers of hepatic stellate cells (HSCs) activation, matrix reorganization and fibrosis including α-smooth muscle actin, transforming growth factor-β1, PDGF-Rβ, pro-inflammatory cytokines and enhanced expression of tissue inhibitor of metalloproteinase-1 and pro(α) collagen type I. Moreover, pro-apoptotic protein Bax was dominantly expressed and Bcl-2 was down-regulated along with increased number of TUNEL positive hepatocytes in liver of arsenic exposed mice. Furthermore, HSCs activation due to increased hepatic oxidative stress observed after in vivo arsenic exposure was recapitulated in co-culture model of isolated HSCs and hepatocytes exposed to arsenic. These findings have implications not only for the understanding of the pathology of arsenic related liver fibrosis but also for the design of preventive strategies in chronic arsenicosis.

  9. Use of the fluorescent micronucleus assay to detect the genotoxic effects of radiation and arsenic exposure in exfoliated human epithelial cells

    International Nuclear Information System (INIS)

    Moore, L.E.; Warner, M.L.; Smith, A.H.

    1996-01-01

    The exfoliated cell micronucleus (MN) assay using fluorescent in situ hybridization (FISH) with a centromeric probe is a rapid method for determining the mechanism of MN formation in epithelial tissues exposed to carcinogenic agents. Here, we describe the use of this assay to detect the presence or absence of centromeric DNA in MN induced in vivo by radiation therapy and chronic arsenic (As) ingestion. We examined the buccal cells of an individual receiving 6,500 rads of photon radiation to the head and neck. Exfoliated cells were collected before, during, and after treatment. After radiation exposure a 16.6-fold increase in buccal cell MN frequency was seen. All induced MN were centromere negative (MN-) resulting from chromosome breakage. This finding is consistent with the clastogenic action of radiation and confirmed the reliability of the method. Three weeks post-therapy, MN frequencies returned to baseline. The assay was used on 18 people chronically exposed to high levels of inorganic arsenic (In-As) in drinking water (average level, 1,312 μg As/L) and 18 matched controls (average level, 16 μg As/L). The combined increase in MN frequency was 1.8-fold (P = 0.001, Fisher's exact test). Frequencies of micronuclei containing acentric fragments (MN-) and those containing whole chromosomes (MN+) both increased, suggesting that arsenic may have both clastogenic and weak aneuploidogenic properties in vivo. After stratification on sex, the effect was stronger in male than in female bladder cells. In males the MN-frequency increased 2.06-fold (P =0.07) while the frequency of MN+ increased 1.86-fold (P = 0.08). In addition, the frequencies of MN and MN+ were positively associated with urinary arsenic and its metabolites. The association was stronger for micronuclei containing acentric fragments. By using FISH with centromeric probes, the mechanism of chemically induced genotoxicity can not be determined in epithelial tissues. 35 refs., 4 tabs

  10. Beam-induced redox transformation of arsenic during As K-edge XAS measurements: availability of reducing or oxidizing agents and As speciation.

    Science.gov (United States)

    Han, Young Soo; Jeong, Hoon Young; Hyun, Sung Pil; Hayes, Kim F; Chon, Chul Min

    2018-05-01

    During X-ray absorption spectroscopy (XAS) measurements of arsenic (As), beam-induced redox transformation is often observed. In this study, the As species immobilized by poorly crystallized mackinawite (FeS) was assessed for the susceptibility to beam-induced redox reactions as a function of sample properties including the redox state of FeS and the solid-phase As speciation. The beam-induced oxidation of reduced As species was found to be mediated by the atmospheric O 2 and the oxidation products of FeS [e.g. Fe(III) (oxyhydr)oxides and intermediate sulfurs]. Regardless of the redox state of FeS, both arsenic sulfide and surface-complexed As(III) readily underwent the photo-oxidation upon exposure to the atmospheric O 2 during XAS measurements. With strict O 2 exclusion, however, both As(0) and arsenic sulfide were less prone to the photo-oxidation by Fe(III) (oxyhydr)oxides than NaAsO 2 and/or surface-complexed As(III). In case of unaerated As(V)-reacted FeS samples, surface-complexed As(V) was photocatalytically reduced during XAS measurements, but arsenic sulfide did not undergo the photo-reduction.

  11. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    International Nuclear Information System (INIS)

    Farzan, Shohreh F.; Chen, Yu; Rees, Judy R.; Zens, M. Scot; Karagas, Margaret R.

    2015-01-01

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US

  12. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    Energy Technology Data Exchange (ETDEWEB)

    Farzan, Shohreh F. [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States); Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY (United States); Chen, Yu [Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY (United States); Rees, Judy R.; Zens, M. Scot [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States); Karagas, Margaret R., E-mail: margaret.r.karagas@dartmouth.edu [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States)

    2015-09-01

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US.

  13. Elucidating the selenium and arsenic metabolic pathways following exposure to the non-hyperaccumulating Chlorophytum comosum, spider plant

    Science.gov (United States)

    Afton, Scott E.; Catron, Brittany; Caruso, Joseph A.

    2009-01-01

    Although many studies have investigated the metabolism of selenium and arsenic in hyperaccumulating plants for phytoremediation purposes, few have explored non-hyperaccumulating plants as a model for general contaminant exposure to plants. In addition, the result of simultaneous supplementation with selenium and arsenic has not been investigated in plants. In this study, Chlorophytum comosum, commonly known as the spider plant, was used to investigate the metabolism of selenium and arsenic after single and simultaneous supplementation. Size exclusion and ion-pairing reversed phase liquid chromatography were coupled to an inductively coupled plasma mass spectrometer to obtain putative metabolic information of the selenium and arsenic species in C. comosum after a mild aqueous extraction. The chromatographic results depict that selenium and arsenic species were sequestered in the roots and generally conserved upon translocation to the leaves. The data suggest that selenium was directly absorbed by C. comosum roots when supplemented with SeVI, but a combination of passive and direct absorption occurred when supplemented with SeIV due to the partial oxidation of SeIV to SeVI in the rhizosphere. Higher molecular weight selenium species were more prevalent in the roots of plants supplemented with SeIV, but in the leaves of plants supplemented with SeVI due to an increased translocation rate. When supplemented as AsIII, arsenic is proposed to be passively absorbed as AsIII and partially oxidized to AsV in the plant root. Although total elemental analysis demonstrates a selenium and arsenic antagonism, a compound containing selenium and arsenic was not present in the general aqueous extract of the plant. PMID:19273464

  14. Estimating Inorganic Arsenic Exposure from U.S. Rice and Total Water Intakes.

    Science.gov (United States)

    Mantha, Madhavi; Yeary, Edward; Trent, John; Creed, Patricia A; Kubachka, Kevin; Hanley, Traci; Shockey, Nohora; Heitkemper, Douglas; Caruso, Joseph; Xue, Jianping; Rice, Glenn; Wymer, Larry; Creed, John T

    2017-05-30

    Among nonoccupationally exposed U.S. residents, drinking water and diet are considered primary exposure pathways for inorganic arsenic (iAs). In drinking water, iAs is the primary form of arsenic (As), while dietary As speciation techniques are used to differentiate iAs from less toxic arsenicals in food matrices. Our goal was to estimate the distribution of iAs exposure rates from drinking water intakes and rice consumption in the U.S. population and ethnic- and age-based subpopulations. The distribution of iAs in drinking water was estimated by population, weighting the iAs concentrations for each drinking water utility in the Second Six-Year Review data set. To estimate the distribution of iAs concentrations in rice ingested by U.S. consumers, 54 grain-specific, production-weighted composites of rice obtained from U.S. mills were extracted and speciated using both a quantitative dilute nitric acid extraction and speciation (DNAS) and an in vitro gastrointestinal assay to provide an upper bound and bioaccessible estimates, respectively. Daily drinking water intake and rice consumption rate distributions were developed using data from the What We Eat in America (WWEIA) study. Using these data sets, the Stochastic Human Exposure and Dose Simulation (SHEDS) model estimated mean iAs exposures from drinking water and rice were 4.2 μg/day and 1.4 μg/day, respectively, for the entire U.S. population. The Tribal, Asian, and Pacific population exhibited the highest mean daily exposure of iAs from cooked rice (2.8 μg/day); the mean exposure rate for children between ages 1 and 2 years in this population is 0.104 μg/kg body weight (BW)/day. An average consumer drinking 1.5 L of water daily that contains between 2 and 3 ng iAs/mL is exposed to approximately the same amount of iAs as a mean Tribal, Asian, and Pacific consumer is exposed to from rice. https://doi.org/10.1289/EHP418. Among nonoccupationally exposed U.S. residents, drinking water and diet are considered

  15. Arsenic tolerant Trichoderma sp. reduces arsenic induced stress in chickpea (Cicer arietinum).

    Science.gov (United States)

    Tripathi, Pratibha; Singh, Poonam C; Mishra, Aradhana; Srivastava, Suchi; Chauhan, Reshu; Awasthi, Surabhi; Mishra, Seema; Dwivedi, Sanjay; Tripathi, Preeti; Kalra, Alok; Tripathi, Rudra D; Nautiyal, Chandra S

    2017-04-01

    Toxic metalloids including arsenic (As) can neither be eliminated nor destroyed from environment; however, they can be converted from toxic to less/non-toxic forms. The form of As species and their concentration determines its toxicity in plants. Therefore, the microbe mediated biotransformation of As is crucial for its plant uptake and toxicity. In the present study the role of As tolerant Trichoderma in modulating As toxicity in chickpea plants was explored. Chickpea plants grown in arsenate spiked soil under green house conditions were inoculated with two plant growth promoting Trichoderma strains, M-35 (As tolerant) and PPLF-28 (As sensitive). Total As concentration in chickpea tissue was comparable in both the Trichoderma treatments, however, differences in levels of organic and inorganic As (iAs) species were observed. The shift in iAs to organic As species ratio in tolerant Trichoderma treatment correlated with enhanced plant growth and nutrient content. Arsenic stress amelioration in tolerant Trichoderma treatment was also evident through rhizospheric microbial community and anatomical studies of the stem morphology. Down regulation of abiotic stress responsive genes (MIPS, PGIP, CGG) in tolerant Trichoderma + As treatment as compared to As alone and sensitive Trichoderma + As treatment also revealed that tolerant strain enhanced the plant's potential to cope with As stress as compared to sensitive one. Considering the bioremediation and plant growth promotion potential, the tolerant Trichoderma may appear promising for its utilization in As affected fields for enhancing agricultural productivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Arsenic induces diabetic effects through beta-cell dysfunction and increased gluconeogenesis in mice

    Science.gov (United States)

    Liu, Su; Guo, Xuechao; Wu, Bing; Yu, Haiyan; Zhang, Xuxiang; Li, Mei

    2014-11-01

    Arsenic as a potential risk factor for type 2 diabetes has been received attention recently. However, the roles of arsenic on development of diabetes are unclear. In this study, we compared the influences of inorganic arsenic (iAs) on normal and diabetic mice by systems toxicology approaches. Although iAs exposure did not change glucose tolerance in normal mice, it caused the pancreatic β-cell dysfunction and increased gluconeogenesis and oxidative damages in liver. However, iAs exposure worsened the glucose tolerance in diabetic mice, which might be due to increased gluconeogenesis and impairment of pancreatic β-cell function. It is interesting that iAs exposure could improve the insulin sensitivity based on the insulin tolerance testing by the activation of glucose uptake-related genes and enzymes in normal and diabetic individuals. Our data suggested that iAs exposure could cause pre-diabetic effects by altering the lipid metabolism, gluconeogenesis and insulin secretion in normal individual, and worsen diabetic effects in diabetes individual by these processes. Insulin resistance might be not the reason of diabetic effects caused by iAs, indicating that mechanism of the diabetogenic effects of iAs exposure is different from the mechanism associated with traditional risk factors (such as obesity)-reduced type 2 diabetes.

  17. Arsenic induces diabetic effects through beta-cell dysfunction and increased gluconeogenesis in mice.

    Science.gov (United States)

    Liu, Su; Guo, Xuechao; Wu, Bing; Yu, Haiyan; Zhang, Xuxiang; Li, Mei

    2014-11-04

    Arsenic as a potential risk factor for type 2 diabetes has been received attention recently. However, the roles of arsenic on development of diabetes are unclear. In this study, we compared the influences of inorganic arsenic (iAs) on normal and diabetic mice by systems toxicology approaches. Although iAs exposure did not change glucose tolerance in normal mice, it caused the pancreatic β-cell dysfunction and increased gluconeogenesis and oxidative damages in liver. However, iAs exposure worsened the glucose tolerance in diabetic mice, which might be due to increased gluconeogenesis and impairment of pancreatic β-cell function. It is interesting that iAs exposure could improve the insulin sensitivity based on the insulin tolerance testing by the activation of glucose uptake-related genes and enzymes in normal and diabetic individuals. Our data suggested that iAs exposure could cause pre-diabetic effects by altering the lipid metabolism, gluconeogenesis and insulin secretion in normal individual, and worsen diabetic effects in diabetes individual by these processes. Insulin resistance might be not the reason of diabetic effects caused by iAs, indicating that mechanism of the diabetogenic effects of iAs exposure is different from the mechanism associated with traditional risk factors (such as obesity)-reduced type 2 diabetes.

  18. Relationship between long-term exposure to low-level arsenic in drinking water and the prevalence of abnormal blood pressure.

    Science.gov (United States)

    Zhang, Chuanwu; Mao, Guangyun; He, Suxia; Yang, Zuopeng; Yang, Wei; Zhang, Xiaojing; Qiu, Wenting; Ta, Na; Cao, Li; Yang, Hui; Guo, Xiaojuan

    2013-11-15

    Arsenic increases the risk and incidence of cardiovascular disease. To explore the impact of long-term exposure to low-level arsenic in drinking water on blood pressure including pulse pressure (PP) and mean arterial blood pressure (MAP), a cross-sectional study was conducted in 2010 in which the blood pressure of 405 villagers was measured, who had been drinking water with an inorganic arsenic content 30-50 years of arsenic exposure and a 2.95-fold (95%CI: 1.31-6.67) increase in the group with >50 years exposure. Furthermore, the odds ratio for prevalence of abnormal PP and MAP were 1.06 (95%CI: 0.24-4.66) and 0.87 (95%CI: 0.36-2.14) in the group with >30-50 years of exposure, and were 2.46 (95%CI: 0.87-6.97) and 3.75 (95%CI: 1.61-8.71) for the group with >50 years exposure, compared to the group with arsenic exposure ≤ 30 years respectively. Significant trends for Hypertension (p<0.0001), PP (p<0.0001) and MAP (p=0.0016) were found. The prevalence of hypertension and abnormal PP as well as MAP is marked among a low-level arsenic exposure population, and significantly increases with the duration of arsenic exposure. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-07-01

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

  20. Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.

    Directory of Open Access Journals (Sweden)

    Syeda Shegufta Ameer

    2016-08-01

    Full Text Available Background: Exposure to inorganic arsenic (iAs through drinking water causes cancer. Alterations in mitochondrial DNA copy number (mtDNAcn and telomere length in blood have been associated with cancer risk. We elucidated if arsenic exposure alters mtDNAcn and telomere length in individuals with different arsenic metabolizing capacity.Methods: We studied two groups in the Salta province, Argentina, one in the Puna area of the Andes (N=264, 89% females and one in Chaco (N=169, 75% females. We assessed arsenic exposure as the sum of arsenic metabolites [iAs, methylarsonic acid (MMA, dimethylarsinic acid (DMA] in urine (U-As using high-performance liquid chromatography coupled with hydride generation and inductively coupled plasma mass spectrometry. Efficiency of arsenic metabolism was expressed as percentage of urinary metabolites. MtDNAcn and telomere length were determined in blood by real-time PCR. Results: Median U-As was 196 (5 - 95 percentile: 21 - 537 µg/L in Andes and 80 (5 - 95 percentile: 15 - 1637 µg/L in Chaco. The latter study group had less-efficient metabolism, with higher %iAs and %MMA in urine compared with the Andean group. U-As was significantly associated with increased mtDNAcn (log2 transformed to improve linearity in Chaco (β=0.027 per 100 µg/L, p=0.0085; adjusted for age and sex, but not in Andes (β=0.025, p=0.24. U-As was also associated with longer telomere length in Chaco (β=0.016, p=0.0066 and Andes (β=0.0075, p=0.029. In both populations, individuals with above median %iAs showed significantly higher mtDNAcn and telomere length compared with individuals with below median %iAs. Conclusions: Arsenic was associated with increased mtDNAcn and telomere length, particularly in individuals with less-efficient arsenic metabolism, a group who may have increased risk for arsenic-related cancer.

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

    Science.gov (United States)

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

    2015-10-01

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

  2. Systems-level modeling the effects of arsenic exposure with sequential pulsed and fluctuating patterns for tilapia and freshwater clam

    International Nuclear Information System (INIS)

    Chen, W.-Y.; Tsai, J.-W.; Ju, Y.-R.; Liao, C.-M.

    2010-01-01

    The purpose of this paper was to use quantitative systems-level approach employing biotic ligand model based threshold damage model to examine physiological responses of tilapia and freshwater clam to sequential pulsed and fluctuating arsenic concentrations. We tested present model and triggering mechanisms by carrying out a series of modeling experiments where we used periodic pulses and sine-wave as featured exposures. Our results indicate that changes in the dominant frequencies and pulse timing can shift the safe rate distributions for tilapia, but not for that of freshwater clam. We found that tilapia increase bioenergetic costs to maintain the acclimation during pulsed and sine-wave exposures. Our ability to predict the consequences of physiological variation under time-varying exposure patterns has also implications for optimizing species growing, cultivation strategies, and risk assessment in realistic situations. - Systems-level modeling the pulsed and fluctuating arsenic exposures.

  3. Systems-level modeling the effects of arsenic exposure with sequential pulsed and fluctuating patterns for tilapia and freshwater clam

    Energy Technology Data Exchange (ETDEWEB)

    Chen, W.-Y. [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Tsai, J.-W. [Institute of Ecology and Evolutionary Ecology, China Medical University, Taichung 40402, Taiwan (China); Ju, Y.-R. [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Liao, C.-M., E-mail: cmliao@ntu.edu.t [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan (China)

    2010-05-15

    The purpose of this paper was to use quantitative systems-level approach employing biotic ligand model based threshold damage model to examine physiological responses of tilapia and freshwater clam to sequential pulsed and fluctuating arsenic concentrations. We tested present model and triggering mechanisms by carrying out a series of modeling experiments where we used periodic pulses and sine-wave as featured exposures. Our results indicate that changes in the dominant frequencies and pulse timing can shift the safe rate distributions for tilapia, but not for that of freshwater clam. We found that tilapia increase bioenergetic costs to maintain the acclimation during pulsed and sine-wave exposures. Our ability to predict the consequences of physiological variation under time-varying exposure patterns has also implications for optimizing species growing, cultivation strategies, and risk assessment in realistic situations. - Systems-level modeling the pulsed and fluctuating arsenic exposures.

  4. Mean total arsenic concentrations in chicken 1989-2000 and estimated exposures for consumers of chicken.

    OpenAIRE

    Lasky, Tamar; Sun, Wenyu; Kadry, Abdel; Hoffman, Michael K

    2004-01-01

    The purpose of this study was to estimate mean concentrations of total arsenic in chicken liver tissue and then estimate total and inorganic arsenic ingested by humans through chicken consumption. We used national monitoring data from the Food Safety and Inspection Service National Residue Program to estimate mean arsenic concentrations for 1994-2000. Incorporating assumptions about the concentrations of arsenic in liver and muscle tissues as well as the proportions of inorganic and organic a...

  5. Molecular effectors in the chronic exposure to arsenic as early and sensitive biomarkers in developing Rhinella arenarum toads

    International Nuclear Information System (INIS)

    Mardirosian, Mariana Noelia; Ceschin, Danilo Guillermo; Lascano, Cecilia Inés; Venturino, Andrés

    2017-01-01

    Highlights: • Arsenic early induces MAPK pathway in R. arenarum embryos and larvae. • The MAPKs MEK-ERK in turn upregulate the transcription factors c-FOS and c-JUN. • SOD, CAT and GST would be affected by ROS at synthesis and degradation level. • Low As levels inducing molecular biomarkers have high probabilities of exceedence. • Molecular biomarkers are most adequate to ascertain As impact in R. arenarum. - Abstract: Arsenic, a natural element of ecological relevance, is one of the most toxic elements present in various regions of the world. It can be found in natural water sources throughout Argentina in concentrations between 0.01 and 15 mg L"–"1. The Argentinean autochthonous toad Rhinella arenarum was selected to study the molecular mechanisms involved in the effects and response to the chronic As exposure along its embryonic and larval development. We evaluated the effects on MAPK signal transduction pathway and transcription factors c-FOS and c-JUN, and the regulation of the expression at protein levels of different antioxidant enzymes. Our results indicated that As is modulating the MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclear fraction along the embryonic development and mainly at the beginning of the larval stage. Through this pathway, As can upregulate transcription factors like c-FOS and c-JUN, impacting the antioxidant response of the exposed embryos and larvae through antioxidant enzymes and recycling of GSH. Arsenic triggered specifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. In particular, the expression levels of SOD, CAT and GST enzymes analyzed by Western blot showed a similar behavior to their enzymatic activities in our previous work. This fact suggests that not only the synthesis of these antioxidant enzymes but also their rapid degradation after inactivation would be regulated in response to ROS levels. Antioxidant enzymes may show dual responses of

  6. Molecular effectors in the chronic exposure to arsenic as early and sensitive biomarkers in developing Rhinella arenarum toads

    Energy Technology Data Exchange (ETDEWEB)

    Mardirosian, Mariana Noelia; Ceschin, Danilo Guillermo; Lascano, Cecilia Inés; Venturino, Andrés, E-mail: a.venturino@conicet.gov.ar

    2017-05-15

    Highlights: • Arsenic early induces MAPK pathway in R. arenarum embryos and larvae. • The MAPKs MEK-ERK in turn upregulate the transcription factors c-FOS and c-JUN. • SOD, CAT and GST would be affected by ROS at synthesis and degradation level. • Low As levels inducing molecular biomarkers have high probabilities of exceedence. • Molecular biomarkers are most adequate to ascertain As impact in R. arenarum. - Abstract: Arsenic, a natural element of ecological relevance, is one of the most toxic elements present in various regions of the world. It can be found in natural water sources throughout Argentina in concentrations between 0.01 and 15 mg L{sup –1}. The Argentinean autochthonous toad Rhinella arenarum was selected to study the molecular mechanisms involved in the effects and response to the chronic As exposure along its embryonic and larval development. We evaluated the effects on MAPK signal transduction pathway and transcription factors c-FOS and c-JUN, and the regulation of the expression at protein levels of different antioxidant enzymes. Our results indicated that As is modulating the MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclear fraction along the embryonic development and mainly at the beginning of the larval stage. Through this pathway, As can upregulate transcription factors like c-FOS and c-JUN, impacting the antioxidant response of the exposed embryos and larvae through antioxidant enzymes and recycling of GSH. Arsenic triggered specifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. In particular, the expression levels of SOD, CAT and GST enzymes analyzed by Western blot showed a similar behavior to their enzymatic activities in our previous work. This fact suggests that not only the synthesis of these antioxidant enzymes but also their rapid degradation after inactivation would be regulated in response to ROS levels. Antioxidant enzymes may show dual responses of

  7. Environmental Exposure to Arsenic, Lead, and Cadmium in People Living near Janghang Copper Smelter in Korea.

    Science.gov (United States)

    Kim, Yong-Dae; Eom, Sang-Yong; Yim, Dong-Hyuk; Kim, In-Soo; Won, Hee-Kwan; Park, Choong-Hee; Kim, Guen-Bae; Yu, Seung-Do; Choi, Byung-Sun; Park, Jung-Duck; Kim, Heon

    2016-04-01

    Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure.

  8. Prenatal exposure to arsenic impairs behavioral flexibility and cortical structure in mice

    Directory of Open Access Journals (Sweden)

    Kyaw Htet eAung

    2016-03-01

    Full Text Available Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although it has been demonstrated that exposure to sodium arsenite (NaAsO2 suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL, which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO2 (85 ppm was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO2 displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO2 exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO2 exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO2 leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment.

  9. Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.

    Directory of Open Access Journals (Sweden)

    Lucio A Ramos-Chávez

    2015-02-01

    Full Text Available Inorganic arsenic (iAs is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH, which is the main antioxidant in the central nervous system. In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females.

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

    Science.gov (United States)

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

  11. Neurobehavioral effects of arsenic exposure among secondary school children in the Kandal Province, Cambodia

    Energy Technology Data Exchange (ETDEWEB)

    Vibol, Sao [United Nations University – International Institute for Global Health, Kuala Lumpur (Malaysia); Faculty of Agricultural Technology and Management, Royal University of Agriculture, Phnom Penh (Cambodia); Hashim, Jamal Hisham, E-mail: jamalhas@hotmail.com [United Nations University – International Institute for Global Health, Kuala Lumpur (Malaysia); Department of Community Health, National University of Malaysia, Kuala Lumpur (Malaysia); Sarmani, Sukiman [Faculty of Science and Technology, National University of Malaysia, Bangi (Malaysia)

    2015-02-15

    The research was carried out at 3 study sites with varying groundwater arsenic (As) levels in the Kandal Province of Cambodia. Kampong Kong Commune was chosen as a highly contaminated site (300–500 μg/L), Svay Romiet Commune was chosen as a moderately contaminated site (50–300 μg/L) and Anlong Romiet Commune was chosen as a control site. Neurobehavioral tests on the 3 exposure groups were conducted using a modified WHO neurobehavioral core test battery. Seven neurobehavioral tests including digit symbol, digit span, Santa Ana manual dexterity, Benton visual retention, pursuit aiming, trail making and simple reaction time were applied. Children's hair samples were also collected to investigate the influence of hair As levels on the neurobehavioral test scores. The results from the inductively coupled plasma-mass spectrometry (ICP-MS) analyses of hair samples showed that hair As levels at the 3 study sites were significantly different (p<0.001), whereby hair samples from the highly contaminated site (n=157) had a median hair As level of 0.93 μg/g, while the moderately contaminated site (n=151) had a median hair As level of 0.22 μg/g, and the control site (n=214) had a median hair As level of 0.08 μg/g. There were significant differences among the 3 study sites for all the neurobehavioral tests scores, except for digit span (backward) test. Multiple linear regression clearly shows a positive significant influence of hair As levels on all the neurobehavioral test scores, except for digit span (backward) test, after controlling for hair lead (Pb), manganese (Mn) and cadmium (Cd). Children with high hair As levels experienced 1.57–4.67 times greater risk of having lower neurobehavioral test scores compared to those with low hair As levels, after adjusting for hair Pb, Mn and Cd levels and BMI status. In conclusion, arsenic-exposed school children from the Kandal Province of Cambodia with a median hair As level of 0.93 µg/g among those from the highly

  12. Neurobehavioral effects of arsenic exposure among secondary school children in the Kandal Province, Cambodia

    International Nuclear Information System (INIS)

    Vibol, Sao; Hashim, Jamal Hisham; Sarmani, Sukiman

    2015-01-01

    The research was carried out at 3 study sites with varying groundwater arsenic (As) levels in the Kandal Province of Cambodia. Kampong Kong Commune was chosen as a highly contaminated site (300–500 μg/L), Svay Romiet Commune was chosen as a moderately contaminated site (50–300 μg/L) and Anlong Romiet Commune was chosen as a control site. Neurobehavioral tests on the 3 exposure groups were conducted using a modified WHO neurobehavioral core test battery. Seven neurobehavioral tests including digit symbol, digit span, Santa Ana manual dexterity, Benton visual retention, pursuit aiming, trail making and simple reaction time were applied. Children's hair samples were also collected to investigate the influence of hair As levels on the neurobehavioral test scores. The results from the inductively coupled plasma-mass spectrometry (ICP-MS) analyses of hair samples showed that hair As levels at the 3 study sites were significantly different (p<0.001), whereby hair samples from the highly contaminated site (n=157) had a median hair As level of 0.93 μg/g, while the moderately contaminated site (n=151) had a median hair As level of 0.22 μg/g, and the control site (n=214) had a median hair As level of 0.08 μg/g. There were significant differences among the 3 study sites for all the neurobehavioral tests scores, except for digit span (backward) test. Multiple linear regression clearly shows a positive significant influence of hair As levels on all the neurobehavioral test scores, except for digit span (backward) test, after controlling for hair lead (Pb), manganese (Mn) and cadmium (Cd). Children with high hair As levels experienced 1.57–4.67 times greater risk of having lower neurobehavioral test scores compared to those with low hair As levels, after adjusting for hair Pb, Mn and Cd levels and BMI status. In conclusion, arsenic-exposed school children from the Kandal Province of Cambodia with a median hair As level of 0.93 µg/g among those from the highly

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

    Directory of Open Access Journals (Sweden)

    Judy Mumford

    2011-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chao-Yuan [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Chu, Jan-Show [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Huang, Shu-Pin [Department of Urology, Kaohsiung Medical University Hospital, College of Medicine Kaohsiung Medical University, Kaohsiung, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Yang, Hsiu-Yuan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Chung, Chi-Jung [Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical Universtiy-Shuang Ho Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2011-12-15

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

  15. Chronic exposure to arsenic, estrogen, and their combination causes increased growth and transformation in human prostate epithelial cells potentially by hypermethylation-mediated silencing of MLH1.

    Science.gov (United States)

    Treas, Justin; Tyagi, Tulika; Singh, Kamaleshwar P

    2013-11-01

    Chronic exposure to arsenic and estrogen is associated with risk of prostate cancer, but their mechanism is not fully understood. Additionally, the carcinogenic effects of their co-exposure are not known. Therefore, the objective of this study was to evaluate the effects of chronic exposure to arsenic, estrogen, and their combination, on cell growth and transformation, and identify the mechanism behind these effects. RWPE-1 human prostate epithelial cells were chronically exposed to arsenic and estrogen alone and in combination. Cell growth was measured by cell count and cell cycle, whereas cell transformation was evaluated by colony formation assay. Gene expression was measured by quantitative real-time PCR and confirmed at protein level by Western blot analysis. MLH1 promoter methylation was determined by pyrosequencing method. Exposure to arsenic, estrogen, and their combinations increases cell growth and transformation in RWPE-1 cells. Increased expression of Cyclin D1 and Bcl2, whereas decreased expression of mismatch repair genes MSH4, MSH6, and MLH1 was also observed. Hypermethylation of MLH1 promoter further suggested the epigenetic inactivation of MLH1 expression in arsenic and estrogen treated cells. Arsenic and estrogen combination caused greater changes than their individual treatments. Findings of this study for the first time suggest that arsenic and estrogen exposures cause increased cell growth and survival potentially through epigenetic inactivation of MLH1 resulting in decreased MLH1-mediated apoptotic response, and consequently increased cellular transformation. © 2013 Wiley Periodicals, Inc.

  16. Arsenic Removal from Groundwater by Solar Driven Inline-Electrolytic Induced Co-Precipitation and Filtration—A Long Term Field Test Conducted in West Bengal

    OpenAIRE

    Otter, Philipp; Malakar, Pradyut; Jana, Bana Bihari; Grischek, Thomas; Benz, Florian; Goldmaier, Alexander; Feistel, Ulrike; Jana, Joydev; Lahiri, Susmita; Alvarez, Juan Antonio

    2017-01-01

    Arsenic contamination in drinking water resources is of major concern in the Ganga delta plains of West Bengal in India and Bangladesh. Here, several laboratory and field studies on arsenic removal from drinking water resources were conducted in the past and the application of strong-oxidant-induced co-precipitation of arsenic on iron hydroxides is still considered as the most promising mechanism. This paper suggests an autonomous, solar driven arsenic removal setting and presents the finding...

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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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 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.

  18. Effects of Nrf2 deficiency on arsenic metabolism in mice.

    Science.gov (United States)

    Wang, Huihui; Zhu, Jiayu; Li, Lu; Li, Yongfang; Lv, Hang; Xu, Yuanyuan; Sun, Guifan; Pi, Jingbo

    2017-12-15

    Inorganic arsenic (iAs) is a known toxicant and carcinogen. Worldwide arsenic exposure has become a threat to human health. The severity of arsenic toxicity is strongly correlated with the speed of arsenic metabolism (methylation) and clearance. Furthermore, oxidative stress is recognized as a major mechanism for arsenic-induced toxicity. Nuclear factor-E2-related factor 2 (Nrf2), a key regulator in cellular adaptive antioxidant response, is clearly involved in alleviation of arsenic-induced oxidative damage. Multiple studies demonstrate that Nrf2 deficiency mice are more vulnerable to arsenic-induced intoxication. However, what effect Nrf2 deficiency might have on arsenic metabolism in mice is still unknown. In the present study, we measured the key enzymes involved in arsenic metabolism in Nrf2-WT and Nrf2-KO mice. Our results showed that basal transcript levels of glutathione S-transferase omega 2 (Gsto2) were significantly higher and GST mu 1 (Gstm1) lower in Nrf2-KO mice compared to Nrf2-WT control. Arsenic speciation and methylation rate in liver and urine was then studied in mice treated with 5mg/kg sodium arsenite for 12h. Although there were some alterations in arsenic metabolism enzymes between Nrf2-WT and Nrf2-KO mice, the Nrf2 deficiency had no significant effect on arsenic methylation. These results suggest that the Nrf2-KO mice are more sensitive to arsenic than Nrf2-WT mainly because of differences in adaptive antioxidant detoxification capacity rather than arsenic methylation capacity. Copyright © 2017. Published by Elsevier Inc.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    In these studies the immunotoxicity of arsenic trioxide (ATO, As 2 O 3 ) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 h per day) at concentrations of 50 μg/m 3 and 1 mg/m 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 μg/g tissue following the 1 mg/m 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 μg/m 3 and 1 mg/m 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.

  1. ARSENIC: A Review on Exposure Pathways, Accumulation, Mobility and Transmission into the Human Food Chain.

    Science.gov (United States)

    Arslan, Beste; Djamgoz, Mustafa B A; Akün, Ertan

    This review deals with exposure pathways of arsenic (As), as well as its transfer and uptake processes from its source to the human body. It is proven fact that uptake of inorganic As for a long period can lead to chronic As poisoning and a variety of adverse health effects such as skin, lung and bladder cancer, in addition to cardiovascular diseases, diabetes and gastrointestinal symptoms. As exposure occurs primarily from consumption of potable water containing high amounts of inorganic As and also from consumption of crops cultivated in As contaminated agricultural fields-either naturally or anthropogenically through contaminated air or pesticides-or irrigated with As containing water. In this review, light is shed on the transfer mechanism of As through the food chain and the parameters that enhance mobility of As in the environment. Amounts of As accumulation in plants and the transfer mechanisms are also quite different. These differences in As accumulation, such as in leaves, stems, fruits and roots, are discussed in detail. Moreover, presence of As in some vegetables consumed is given by investigating recent research articles that deal with As concentrations, especially in edible parts. Some comparative data are also presented, concerning the level of concentration of As in rice during washing, cooking and processing stages.

  2. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lingzhi; Qiu, Ping; Chen, Bailing; Lu, Yongju; Wu, Kai; Thakur, Chitra; Chang, Qingshan; Sun, Jiaying; Chen, Fei, E-mail: fchen@wayne.edu

    2014-05-01

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.

  3. Proteomic analysis of an environmental isolate of Rhodotorula mucilaginosa after arsenic and cadmium challenge: Identification of a protein expression signature for heavy metal exposure.

    Science.gov (United States)

    Ilyas, Sidra; Rehman, Abdul; Coelho, Ana Varela; Sheehan, David

    2016-06-01

    A metal-resistant Rhodotorula mucilaginosa strain was isolated from an industrial wastewater. Effects on reduced/oxidized glutathione (GSSG/GSH), antioxidant enzymes and proteome were assessed on metal challenge (100mg/L). Increased GSH (mM/g) was found with CdCl2 (18.43±3.34), NaAsO2 (14.76±2.14), CuSO4 (14.73±2.49), and Pb(NO3)2 (15.74±5.3) versus control (7.67±0.95). GSH:GSSG ratio decreased with CdCl2, NaAsO2, and Pb(NO3)2 but not with CuSO4 and cysteine-containing protein levels increased with CdCl2 and NaAsO2. NaAsO2 exposure enhanced glutathione transferase activity but this decreased with CdCl2. Both metals significantly increased glutathione reductase and catalase activities. Metabolism-dependent uptake of Cd and As (12-day exposure) of approximately 65mg/g was observed in live cells with greater cell surface interaction for As compared to Cd. A particular role for arsenic oxidase in As resistance was identified. One dimensional electrophoresis revealed higher oxidation of protein thiols in response to NaAsO2 than to CdCl2. Two dimensional electrophoresis showed altered abundance of some proteins on metal treatment. Selected spots were excised for mass spectrometry and seven proteins identified. Under oxidative stress conditions, xylose reductase, putative chitin deacetylase, 20S proteasome subunit, eukaryotic translation elongation factor 2, valine-tRNA ligase and a metabolic enzyme F0F1 ATP synthase alpha subunit were all expressed as well as a unique hypothetical protein. These may comprise a protein expression signature for metal-induced oxidation in this yeast. Fungi are of widespread importance in agriculture, biodegradation and often show extensive tolerance to heavy metals. This makes them of interest from the perspective of bioremediation. In this study an environmental isolate of R. mucilaginosa showing extensive tolerance of a panel of heavy metals, in particular cadmium and arsenic, was studied. Several biochemical parameters such as

  4. Design of a rural water provision system to decrease arsenic exposure in Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Mathieu, Johanna [Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2009-01-09

    Researchers at the Lawrence Berkeley National Laboratory have invented ARUBA (Arsenic Removal Using Bottom Ash) a material that effectively and affordably removes high concentrations of arsenic from contaminated groundwater. The technology is cost-effective because the substrate-bottom ash from coal fired power plants-is a waste material readily available in South Asia. During fieldwork in four sub-districts of Bangladesh, ARUBA reduced groundwater arsenic concentrations as high as 680 ppb to below the Bangladesh standard of 50 ppb. Key results from three trips in Bangladesh and one trip to Cambodia include (1) ARUBA removes more than half of the arsenic from contaminated water within the first five minutes of contact, and continues removing arsenic for 2-3 days; (2) ARUBA's arsenic removal efficiency can be improved through fractionated dosing (adding a given amount of ARUBA in fractions versus all at once); (3) allowing water to first stand for two to three days followed by treatment with ARUBA produced final arsenic concentrations ten times lower than treating water directly out of the well; and (4) the amount of arsenic removed per gram of ARUBA is linearly related to the initial arsenic concentration of the water. Through analysis of existing studies, observations, and informal interviews in Bangladesh, eight design strategies have been developed and used in the design of a low-cost, community-scale water treatment system that uses ARUBA to remove arsenic from drinking water. We have constructed, tested, and analyzed a scale version of the system. Experiments have shown that the system is capable of reducing high levels of arsenic (nearly 600 ppb) to below 50 ppb, while remaining affordable to people living on less than $2 per day. The system could be sustainably implemented as a public-private partnership in rural Bangladesh.

  5. Analysis of the risk of disease associated with arsenic exposure in water supply systems for human consumption

    International Nuclear Information System (INIS)

    Villegas Gonzalez, Nicole

    2014-01-01

    The risk of disease associated with arsenic exposure is analyzed in water supply systems for human consumption, as well as the control of pollution and effects on health, in the community known as Barrio Hotel of Canas in comparison with the community of San Miguel in Canas, Guanacaste, Costa Rica. A spatial analysis, temporal and classification are realized by an ecological design of the country in the following zones of exposure: without exposure, low (≥3 μg/L and ≤10 μg/L) and medium to high (≥11 μg/L and ≤187 μg/L). The transversal design is tackled through the perceived morbidity. Spatial analysis has found in the districts of Bebedero, Los Chiles, Bagaces and Canas with Standardized Morbidity Index (EMI) by age in the the greatest national range of chronic renal failure (CRF). The protection of skin cancer risk is observed in the communities of Bagaces, Canas, El Amparo and La Cruz. A temporal trend of increase in IME of CRF and skin cancer is identified in Los Chiles. The classification by zone of exposure, the unexposed areas have been protected of kidney cancer, lung and bronchus, bladder and skin. The of low exposure have presented excess risk of CRF and have been protected of skin cancer. The of medium to high are protected of bladder cancer and have maintained the trend of excess in CRF and protection of skin cancer. The transversal design has found in the exposed community the risk to suffer kidneys diseases. Arsenic exposure has increased in men the risk of renal failure and anemia, in women the decrease of vision, and age groups under of 10 years and of 40-69 years of hypopigmentation and keratoses respectively. Multivariate analysis has showed a weak association of arsenic exposure time with the risk of hypertension [es

  6. Subchronic Exposure to Arsenic Represses the TH/TRβ1-CaMK IV Signaling Pathway in Mouse Cerebellum

    Directory of Open Access Journals (Sweden)

    Huai Guan

    2016-01-01

    Full Text Available We previously reported that arsenic (As impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR/retinoid X receptor (RXR heterodimer and thyroid hormone (TH may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3’-triiodothyronine (T3 and thyroxin (T4 levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRβ gene, and TRβ1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRβ1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRβ1 and CaMK IV in cerebellum and that the down-regulated TRβ1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway.

  7. Subchronic Exposure to Arsenic Represses the TH/TRβ1-CaMK IV Signaling Pathway in Mouse Cerebellum.

    Science.gov (United States)

    Guan, Huai; Li, Shuangyue; Guo, Yanjie; Liu, Xiaofeng; Yang, Yi; Guo, Jinqiu; Li, Sheng; Zhang, Cong; Shang, Lixin; Piao, Fengyuan

    2016-01-26

    We previously reported that arsenic (As) impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV) in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR)/retinoid X receptor (RXR) heterodimer and thyroid hormone (TH) may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3'-triiodothyronine (T3) and thyroxin (T4) levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM) tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRβ gene, and TRβ1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRβ1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRβ1 and CaMK IV in cerebellum and that the down-regulated TRβ1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway.

  8. Pre-cancerous changes in urothelial endocytic vesicle leakage, fatty acid composition, and As and associated element concentrations after arsenic exposure

    International Nuclear Information System (INIS)

    Grasso, E.J.; Bongiovanni, G.A.; Perez, R.D.; Calderon, R.O.

    2011-01-01

    The urothelium covering the luminal surface of the urinary bladder has developed an efficient permeability barrier that protects it against the back-flow of toxins eliminated in the urine. The subapical endocytic vesicles containing the urinary bladder fluid phase are formed during the micturition cycle by endocytosis processes of the superficial cells. In normal conditions, the permeability barrier of the endocytic vesicles blocks the passage of the fluid phase to the cellular cytoplasm and the fluid is recycled to the bladder lumen. The aim of this work was to investigate the alteration of the endocytic vesicle membrane permeability barrier to toxins such as iAs (inorganic arsenic) administered in drinking water. By using an induced endocytosis model and the fluorescence requenching technique, it is shown that the exposure of rats to ingestion of water containing iAs not only induced pre-cancerous morphological changes, but allowed the differential leakage of an endocytosed fluorescent marker, HPTS, and its quencher, DPX, (hydroxypyrene-1,3,6-trisulfonic acid and p-xylene-bis-pyridinium bromide, respectively) out of the vesicular lumen. The leakage of the cationic DPX was almost complete, while the release of the anionic HPTS molecule was partial and higher in arsenic-treated-rats than in controls. Such membrane alteration would allow the toxins to elude the permeability barrier and to leak out of the endocytic vesicles, thus establishing a 'bypass' to the permeability barrier. The retention of As in the urinary bladder, assessed by synchrotron radiation X-ray fluorescence spectrometry (SR-μXRF), was lower than the kidney accumulation of arsenic previously observed by our group and was accompanied by altered concentrations of K, Ca, Fe, Cu and Zn, all ions related to cellular metabolism. The results support the hypothesis that low amounts of endocytosed As can accumulate in the interior of the urothelial superficial cells and initiate the cytotoxic effects

  9. Adverse health effects due to arsenic exposure: Modification by dietary supplementation of jaggery in mice

    International Nuclear Information System (INIS)

    Singh, Nrashant; Kumar, D.; Lal, Kewal; Raisuddin, S.; Sahu, Anand P.

    2010-01-01

    Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene and other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1β, interleukin-6 and TNF-α were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic.

  10. Adverse health effects due to arsenic exposure: modification by dietary supplementation of jaggery in mice.

    Science.gov (United States)

    Singh, Nrashant; Kumar, D; Lal, Kewal; Raisuddin, S; Sahu, Anand P

    2010-02-01

    Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene and other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1beta, interleukin-6 and TNF-alpha were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic. Copyright 2009 Elsevier Inc. All rights reserved.

  11. Vascular Hyperpermeability Response in Animals Systemically Exposed to Arsenic.

    Science.gov (United States)

    Chen, Shih-Chieh; Chang, Chao-Yuah; Lin, Ming-Lu

    2018-01-01

    The mechanisms underlying cardiovascular diseases induced by chronic exposure to arsenic remain unclarified. The objectives of this study were to investigate whether increased vascular leakage is induced by inflammatory mustard oil in mice systemically exposed to various doses of arsenic and whether an increased vascular leakage response is still present in arsenic-fed mice after arsenic discontinuation for 2 or 6 months. ICR mice were fed water or various doses of sodium arsenite (10, 15, or 20 mg/kg/day; 5 days/week) for 8 weeks. In separate experiments, the mice were treated with sodium arsenite (20 mg/kg) for 2 or 8 weeks, followed by arsenic discontinuation for 2 or 6 months. Vascular permeability to inflammatory mustard oil was quantified using Evans blue (EB) techniques. Both arsenic-exposed and water-fed (control) mice displayed similar basal levels of EB leakage in the ears brushed with mineral oil, a vehicle of mustard oil. The levels of EB leakage induced by mustard oil in the arsenic groups fed with sodium arsenite (10 or 15 mg/kg) were similar to those of water-fed mice. However, increased levels of EB leakage in response to mustard oil stimulation were significantly higher in mice treated with sodium arsenite (20 mg/kg; high dose) than in arsenic-fed (10 or 15 mg/kg; low and middle doses) or control mice. After arsenic discontinuation for 2 or 6 months, mustard oil-induced vascular EB leakage in arsenic-fed (20 mg/kg) mice was similar to that in control mice. Dramatic increases in mustard oil-induced vascular leakage were only present in mice systemically exposed to the high arsenic dose, indicating the synergistic effects of the high arsenic dose and mustard oil.

  12. Phytate induced arsenic uptake and plant growth in arsenic-hyperaccumulator Pteris vittata.

    Science.gov (United States)

    Liu, Xue; Fu, Jing-Wei; Tang, Ni; da Silva, E B; Cao, Yue; Turner, Benjamin L; Chen, Yanshan; Ma, Lena Q

    2017-07-01

    Phytate is abundant in soils, which is stable and unavailable for plant uptake. However, it occurs in root exudates of As-hyperaccumulator Pteris vittata (PV). To elucidate its effect on As uptake and growth, P. vittata were grown on agar media (63 μM P) containing 50 μM As and/or 50 or 500 μM phytate with non As-hyperaccumulator Pteris ensiformis (PE) as a congeneric control for 60 d. Phytate induced efficient As and P uptake, and enhanced growth in PV, but had little effects on PE. The As concentrations in PV fronds and roots were 157 and 31 mg kg -1 in As 50 +phytate 50 , 2.2- and 3.1-fold that of As 50 treatment. Phosphorus uptake by PV was reduced by 27% in As treatment than the control (P vs. P+As) but increased by 73% comparing phytate 500 to phytate 500 +As, indicating that PV effectively took up P from phytate. Neither As nor phytate affected Fe accumulation in PV, but phytate reduced root Fe concentration in PE (46-56%). As such, the increased As and P and the unsuppressed Fe uptake in PV probably promoted PV growth. Thus, supplying phytate to As-contaminated soils may promote As uptake and growth in PV and its phytoremediation ability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Impact on arsenic exposure of a growing proportion of untested wells in Bangladesh

    Directory of Open Access Journals (Sweden)

    George Christine

    2012-02-01

    Full Text Available Abstract Background In many areas of Bangladesh, it has been more than six years since a national campaign to test tubewells for arsenic (As was conducted. Many households therefore draw their water for drinking and cooking from untested wells. Methods A household drinking water survey of 6646 households was conducted in Singair upazilla of Bangladesh. A subset of 795 untested wells used by 1000 randomly selected households was tested in the field by trained village workers with the Hach EZ kit, using an extended reaction time of 40 min, and in the laboratory by high-resolution inductively-coupled plasma-mass spectrometry (HR ICP-MS. Results The household survey shows that more than 80% of the wells installed since the national testing campaign in this area were untested. Less than 13% of the households with untested wells knew where a low-As well was located near their home. Village workers using the Hach EZ kit underestimated the As content of only 4 out of 795 wells relative to the Bangladesh standard. However, the As content of 168 wells was overestimated relative to the same threshold. Conclusion There is a growing need for testing tubewells in areas of Bangladesh where As concentrations in groundwater are elevated. This could be achieved by village workers trained to use a reliable field kit. Such an effort would result in a considerable drop in As exposure as it increases the opportunities for well switching by households.

  14. Betel quid chewing elevates human exposure to arsenic, cadmium and lead

    Energy Technology Data Exchange (ETDEWEB)

    Al-Rmalli, Shaban W.; Jenkins, Richard O. [Faculty of Health and Life Sciences, De Montfort University, The Gateway, Leicester LE1 9BH (United Kingdom); Haris, Parvez I., E-mail: pharis@dmu.ac.uk [Faculty of Health and Life Sciences, De Montfort University, The Gateway, Leicester LE1 9BH (United Kingdom)

    2011-06-15

    Several studies have reported increased skin lesions in betel quid (a mixture of Piper betel leaves, areca nut, tobacco/flavoured tobacco, lime) chewers compared to non-chewers, exposed to arsenic (As) contaminated drinking water in Bangladesh and India. The current study has determined As, cadmium (Cd) and lead (Pb) levels of betel quids and its components using inductively coupled plasma mass spectrometry (ICP-MS). The highest concentrations of As were found in slaked lime (4.56 mg kg{sup -1}) followed by Piper betel leaves (0.406 mg kg{sup -1}) and flavoured tobacco (zarda) (0.285 mg kg{sup -1}), with a mean concentrations of As in betel quids of 0.035 mg kg{sup -1} (SD 0.02 mg kg{sup -1}). Mean concentrations of Cd and Pb in ordinary quids were 0.028 (SD 0.07 mg kg{sup -1}) and 0.423 (SD 1.4 mg kg{sup -1}), respectively. We estimated that a daily intake of 6 betel quids could contribute 1.2, 1.9 and 8.5% of the provisional maximum tolerable daily intake (PMDTI) for As, Cd and Pb, respectively. Since betel quid chewing is most prevalent among women, our finding raises concern that women chewers - especially pregnant chewers - may be harming their health and that of their unborn babies through increased exposure to a mixture of toxic elements (As, Cd and Pb).

  15. [Geographic distribution and exposure population of drinking water with high concentration of arsenic in China].

    Science.gov (United States)

    Zhang, L; Chen, C

    1997-09-01

    According to the data obtained from the "National Survey on Drinking Water Quality and Waterborne Diseases", the geographic distribution and exposure population of high arsenic drinking water were reported. From the data of more than 28,800 water samples, we found 9.02 million people drinking the water with As concentration of 0.030-0.049 mg/L, 3.34 million people having their water of 0.050-0.099 mg/L and 2.29 million people having water of > 0.1 mg/L. A total of 14.6 million people, about 1.5% of the surveyed population was exposed to As (> 0.030 mg/L) from drinking water. 80% of high-As-drinking water was groundwater. The situation of As in drinking water in provinces, autonomous regions and municipalities were listed. The locations of sampling site where water As exceeded the national standard for drinking water were illustrated.

  16. Betel quid chewing elevates human exposure to arsenic, cadmium and lead.

    Science.gov (United States)

    Al-Rmalli, Shaban W; Jenkins, Richard O; Haris, Parvez I

    2011-06-15

    Several studies have reported increased skin lesions in betel quid (a mixture of Piper betel leaves, areca nut, tobacco/flavoured tobacco, lime) chewers compared to non-chewers, exposed to arsenic (As) contaminated drinking water in Bangladesh and India. The current study has determined As, cadmium (Cd) and lead (Pb) levels of betel quids and its components using inductively coupled plasma mass spectrometry (ICP-MS). The highest concentrations of As were found in slaked lime (4.56 mg kg(-1)) followed by Piper betel leaves (0.406 mg kg(-1)) and flavoured tobacco (zarda) (0.285 mg kg(-1)), with a mean concentrations of As in betel quids of 0.035 mg kg(-1) (SD 0.02 mg kg(-1)). Mean concentrations of Cd and Pb in ordinary quids were 0.028 (SD 0.07 mg kg(-1)) and 0.423 (SD 1.4 mg kg(-1)), respectively. We estimated that a daily intake of 6 betel quids could contribute 1.2, 1.9 and 8.5% of the provisional maximum tolerable daily intake (PMDTI) for As, Cd and Pb, respectively. Since betel quid chewing is most prevalent among women, our finding raises concern that women chewers - especially pregnant chewers - may be harming their health and that of their unborn babies through increased exposure to a mixture of toxic elements (As, Cd and Pb). Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Betel quid chewing elevates human exposure to arsenic, cadmium and lead

    International Nuclear Information System (INIS)

    Al-Rmalli, Shaban W.; Jenkins, Richard O.; Haris, Parvez I.

    2011-01-01

    Several studies have reported increased skin lesions in betel quid (a mixture of Piper betel leaves, areca nut, tobacco/flavoured tobacco, lime) chewers compared to non-chewers, exposed to arsenic (As) contaminated drinking water in Bangladesh and India. The current study has determined As, cadmium (Cd) and lead (Pb) levels of betel quids and its components using inductively coupled plasma mass spectrometry (ICP-MS). The highest concentrations of As were found in slaked lime (4.56 mg kg -1 ) followed by Piper betel leaves (0.406 mg kg -1 ) and flavoured tobacco (zarda) (0.285 mg kg -1 ), with a mean concentrations of As in betel quids of 0.035 mg kg -1 (SD 0.02 mg kg -1 ). Mean concentrations of Cd and Pb in ordinary quids were 0.028 (SD 0.07 mg kg -1 ) and 0.423 (SD 1.4 mg kg -1 ), respectively. We estimated that a daily intake of 6 betel quids could contribute 1.2, 1.9 and 8.5% of the provisional maximum tolerable daily intake (PMDTI) for As, Cd and Pb, respectively. Since betel quid chewing is most prevalent among women, our finding raises concern that women chewers - especially pregnant chewers - may be harming their health and that of their unborn babies through increased exposure to a mixture of toxic elements (As, Cd and Pb).

  18. Arsenic, Cadmium and Lead Exposure and Immunologic Function in Workers in Taiwan.

    Science.gov (United States)

    Wu, Chin-Ching; Sung, Fung-Chang; Chen, Yi-Chun

    2018-04-05

    There has been growing concern over the impact of environmental exposure to heavy metals and other trace elements on immunologic functions. This study investigated men's arsenic (As), cadmium (Cd) and lead (Pb) contents in hair samples and their associations with immunological indicators, including white blood cell (WBC), lymphocyte and monocyte counts, and the immunoglobulin (Ig) levels including IgA, IgG and IgE. We recruited 133 men from one antimony trioxide manufacturing plant, two glass manufacturing plants and two plastics manufacturing plants. The mean concentration of Cd [0.16 (SD = 0.03) ug/g] was lower than means of As [0.86 (SD = 0.16) ug/g] and Pb [0.91 (SD = 0.22) ug/g] in hair samples, exerting no relationship with immunologic functions for Cd. The Spearman's correlation analysis showed a positive relationship between monocyte counts and hair Pb levels, but negative relations between As and IgG and between As and IgE. In conclusion, findings from these industry workers suggest that As levels in hair may have a stronger relation with immunologic function than Cd and PB have. Further research is needed to confirm the negative relationship.

  19. Arsenic, Cadmium and Lead Exposure and Immunologic Function in Workers in Taiwan

    Directory of Open Access Journals (Sweden)

    Chin-Ching Wu

    2018-04-01

    Full Text Available There has been growing concern over the impact of environmental exposure to heavy metals and other trace elements on immunologic functions. This study investigated men’s arsenic (As, cadmium (Cd and lead (Pb contents in hair samples and their associations with immunological indicators, including white blood cell (WBC, lymphocyte and monocyte counts, and the immunoglobulin (Ig levels including IgA, IgG and IgE. We recruited 133 men from one antimony trioxide manufacturing plant, two glass manufacturing plants and two plastics manufacturing plants. The mean concentration of Cd [0.16 (SD = 0.03 ug/g] was lower than means of As [0.86 (SD = 0.16 ug/g] and Pb [0.91 (SD = 0.22 ug/g] in hair samples, exerting no relationship with immunologic functions for Cd. The Spearman’s correlation analysis showed a positive relationship between monocyte counts and hair Pb levels, but negative relations between As and IgG and between As and IgE. In conclusion, findings from these industry workers suggest that As levels in hair may have a stronger relation with immunologic function than Cd and PB have. Further research is needed to confirm the negative relationship.

  20. ARSENIC SPECIATION ANALYSIS IN HUMAN SALIVA

    Science.gov (United States)

    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 ...

  1. Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

    Science.gov (United States)

    Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

    2012-11-30

    Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.

    Science.gov (United States)

    Perry, Meghan R; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H

    2013-12-03

    The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg · mL(-1) Pentostam compared with the control passage group (38.5 μg · mL(-1)) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is.

  3. Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetes

    International Nuclear Information System (INIS)

    Paul, David S.; Hernandez-Zavala, Araceli; Walton, Felecia S.; Adair, Blakely M.; Dedina, Jiri; Matousek, Tomas; Styblo, Miroslav

    2007-01-01

    Previous epidemiologic studies found increased prevalences of type 2 diabetes mellitus in populations exposed to high levels of inorganic arsenic (iAs) in drinking water. Although results of epidemiologic studies in low-exposure areas or occupational settings have been inconclusive, laboratory research has shown that exposures to iAs can produce effects that are consistent with type 2 diabetes. The current paper reviews the results of laboratory studies that examined the effects of iAs on glucose metabolism and describes new experiments in which the diabetogenic effects of iAs exposure were reproduced in a mouse model. Here, weanling male C57BL/6 mice drank deionized water with or without the addition of arsenite (25 or 50 ppm As) for 8 weeks. Intraperitoneal glucose tolerance tests revealed impaired glucose tolerance in mice exposed to 50 ppm As, but not to 25 ppm As. Exposure to 25 and 50 ppm As in drinking-water resulted in proportional increases in the concentration of iAs and its metabolites in the liver and in organs targeted by type 2 diabetes, including pancreas, skeletal muscle and adipose tissue. Dimethylarsenic was the predominant form of As in the tissues of mice in both 25 and 50 ppm groups. Notably, the average concentration of total speciated arsenic in livers from mice in the 50 ppm group was comparable to the highest concentration of total arsenic reported in the livers of Bangladeshi residents who had consumed water with an order of magnitude lower level of iAs. These data suggest that mice are less susceptible than humans to the diabetogenic effects of chronic exposure to iAs due to a more efficient clearance of iAs or its metabolites from target tissues

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

    Science.gov (United States)

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

    2017-12-01

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

  5. Radiation-induced physical ageing in network arsenic-sulfide/selenide glasses

    International Nuclear Information System (INIS)

    Shpotyuk, M; Golovchak, R; Kozdras, A; Shpotyuk, O

    2010-01-01

    Effect of radiation-induced physical ageing is investigated by differential scanning calorimetry method in As x Se 100-x (10 ≤ x ≤ 42) and As x S 100-x (30 ≤ x ≤ 42) glasses. Obtained results are compared with conventional physical ageing at normal conditions. Significant radiation-induced physical ageing is recorded for glassy As x S 100-x within 30 ≤ x x Se 100-x glasses from the same compositional interval do not show any measurable changes in DSC curves after γ-irradiation. Observed difference in radiation-induced physical ageing in arsenic-sulfide/selenide glasses is explained by a greater lifetime of γ-induced excitations within sulfur-based network in comparison with selenium-based one.

  6. Radiation-induced physical ageing in network arsenic-sulfide/selenide glasses

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, M; Golovchak, R; Kozdras, A; Shpotyuk, O, E-mail: shpotyuk@novas.lviv.ua

    2010-11-15

    Effect of radiation-induced physical ageing is investigated by differential scanning calorimetry method in As{sub x}Se{sub 100-x} (10 {<=} x {<=} 42) and As{sub x}S{sub 100-x} (30 {<=} x {<=} 42) glasses. Obtained results are compared with conventional physical ageing at normal conditions. Significant radiation-induced physical ageing is recorded for glassy As{sub x}S{sub 100-x} within 30 {<=} x < 40 range, while As{sub x}Se{sub 100-x} glasses from the same compositional interval do not show any measurable changes in DSC curves after {gamma}-irradiation. Observed difference in radiation-induced physical ageing in arsenic-sulfide/selenide glasses is explained by a greater lifetime of {gamma}-induced excitations within sulfur-based network in comparison with selenium-based one.

  7. Morbid condition involving cardio-vascular, broncho-pulmonary, digestive and neural lesions in children and young adults after dietary arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Zaldivar, R.

    1980-02-01

    An investigation on the relationship between dietary arsenic exposure and cardiovascular diseases was made. In Antofagasta Commune, northern Chile, since 1955 arsenic has polluted public drinking water. This environmental contamination is of geological origin. The concentration of arsenic in drinking water for the 1955 to 1970 period was 0.5980 ppM. In the period June 1970 to March 1972, the concentration decreased to 0.0815 ppM due to a water filtration plant which started operating in May 1970. Greater Santiago showed 0.00 ppM of arsenic in drinking water. Amongst 10 autopsied patients with chronic arsenical dermatosis from Antofagasta Commune, 9 showed marked fibrous intimal thickening of the arterial wall and/or restricted lumen of the left coronary artery, 2 of these 9 also exhibiting myocardial infarction. Of the 10 patients, 7 developed cardiomegaly, which was related to chronic exposure to dietary arsenic. Two series of patients with myocardial infarction under 40 years of age, one from Antofagasta Commune, the other from greater Santiago (not exposed to arsenic) were compared. The Yates corrected chi 2 value being 11.7776. The difference was statistically highly significant. In Antofagasta Commune, the number of cases which had myocardial infarction with chronic arsenical dermatosis were compared with the cases which showed, myocardial infarction without chronic arsenical dermatosis. The Yates corrected chi 2 value was 13.0395. A highly significant difference was detected. Children from the two cities were also compared. The number of cases with myocardial infarction showed a significant difference; Fisher's exact test yielded a P approximately equal to 0.004944, the Yates corrected chi 2 value being 20.7311. The number of children with systemic occlusive arterial disease from the two cities also exhibited a highly significant difference.

  8. Arsenic and diabetes and hypertension in human populations: A review

    International Nuclear Information System (INIS)

    Chen, C.-J.; Wang, S.-L.; Chiou, J.-M.; Tseng, C.-H.; Chiou, H.-Y.; Hsueh, Y.-M.; Chen, S.-Y.; Wu, M.-M.; Lai, M.-S.

    2007-01-01

    Long-term exposure to ingested arsenic from drinking water has been well documented to be associated with an increased risk of diabetes mellitus and hypertension in a dose-response relationship among residents of arseniasis-endemic areas in southwestern Taiwan and Bangladesh. An increased risk of self-reported hypertension but not diabetes was reported in a community-based study of residents who consumed drinking water with a low level of arsenic. Increased glycosylated hemoglobin level and systolic blood pressure were observed in workers occupationally exposed to arsenic. Inconsistent findings of arsenic and diabetes in occupational studies may result from the healthy worker effect and the variation in exposure measurement, age composition, number of patients, accuracy in diagnosis and classification of underlying causes of death, competing causes of death, and method to detect diabetes. The dose-response relationship and toxicological mechanisms of arsenic-induced diabetes and hypertension need further elucidation

  9. Developmental exposure to 50 parts-per-billion arsenic influences histone modifications and associated epigenetic machinery in a region- and sex-specific manner in the adult mouse brain

    International Nuclear Information System (INIS)

    Tyler, Christina R.; Hafez, Alexander K.; Solomon, Elizabeth R.; Allan, Andrea M.

    2015-01-01

    Epidemiological studies report that arsenic exposure via drinking water adversely impacts cognitive development in children and, in adults, can lead to greater psychiatric disease susceptibility, among other conditions. While it is known that arsenic toxicity has a profound effect on the epigenetic landscape, very few studies have investigated its effects on chromatin architecture in the brain. We have previously demonstrated that exposure to a low level of arsenic (50 ppb) during all three trimesters of fetal/neonatal development induces deficits in adult hippocampal neurogenesis in the dentate gyrus (DG), depressive-like symptoms, and alterations in gene expression in the adult mouse brain. As epigenetic processes control these outcomes, here we assess the impact of our developmental arsenic exposure (DAE) paradigm on global histone posttranslational modifications and associated chromatin-modifying proteins in the dentate gyrus and frontal cortex (FC) of adult male and female mice. DAE influenced histone 3 K4 trimethylation with increased levels in the male DG and FC and decreased levels in the female DG (no change in female FC). The histone methyltransferase MLL exhibited a similar sex- and region-specific expression profile as H3K4me3 levels, while histone demethylase KDM5B expression trended in the opposite direction. DAE increased histone 3 K9 acetylation levels in the male DG along with histone acetyltransferase (HAT) expression of GCN5 and decreased H3K9ac levels in the male FC along with decreased HAT expression of GCN5 and PCAF. DAE decreased expression of histone deacetylase enzymes HDAC1 and HDAC2, which were concurrent with increased H3K9ac levels but only in the female DG. Levels of H3 and H3K9me3 were not influenced by DAE in either brain region of either sex. These findings suggest that exposure to a low, environmentally relevant level of arsenic during development leads to long-lasting changes in histone methylation and acetylation in the adult

  10. Developmental exposure to 50 parts-per-billion arsenic influences histone modifications and associated epigenetic machinery in a region- and sex-specific manner in the adult mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Tyler, Christina R.; Hafez, Alexander K.; Solomon, Elizabeth R.; Allan, Andrea M., E-mail: aallan@salud.unm.edu

    2015-10-01

    Epidemiological studies report that arsenic exposure via drinking water adversely impacts cognitive development in children and, in adults, can lead to greater psychiatric disease susceptibility, among other conditions. While it is known that arsenic toxicity has a profound effect on the epigenetic landscape, very few studies have investigated its effects on chromatin architecture in the brain. We have previously demonstrated that exposure to a low level of arsenic (50 ppb) during all three trimesters of fetal/neonatal development induces deficits in adult hippocampal neurogenesis in the dentate gyrus (DG), depressive-like symptoms, and alterations in gene expression in the adult mouse brain. As epigenetic processes control these outcomes, here we assess the impact of our developmental arsenic exposure (DAE) paradigm on global histone posttranslational modifications and associated chromatin-modifying proteins in the dentate gyrus and frontal cortex (FC) of adult male and female mice. DAE influenced histone 3 K4 trimethylation with increased levels in the male DG and FC and decreased levels in the female DG (no change in female FC). The histone methyltransferase MLL exhibited a similar sex- and region-specific expression profile as H3K4me3 levels, while histone demethylase KDM5B expression trended in the opposite direction. DAE increased histone 3 K9 acetylation levels in the male DG along with histone acetyltransferase (HAT) expression of GCN5 and decreased H3K9ac levels in the male FC along with decreased HAT expression of GCN5 and PCAF. DAE decreased expression of histone deacetylase enzymes HDAC1 and HDAC2, which were concurrent with increased H3K9ac levels but only in the female DG. Levels of H3 and H3K9me3 were not influenced by DAE in either brain region of either sex. These findings suggest that exposure to a low, environmentally relevant level of arsenic during development leads to long-lasting changes in histone methylation and acetylation in the adult

  11. Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

    International Nuclear Information System (INIS)

    Straub, Adam C.; Stolz, Donna B.; Vin, Harina; Ross, Mark A.; Soucy, Nicole V.; Klei, Linda R.; Barchowsky, Aaron

    2007-01-01

    The vascular effects of arsenic in drinking water are global health concerns contributing to human disease worldwide. Arsenic targets the endothelial cells lining blood vessels, and endothelial cell activation or dysfunction may underlie the pathogenesis of both arsenic-induced vascular diseases and arsenic-enhanced tumorigenesis. The purpose of the current studies was to demonstrate that exposing mice to drinking water containing environmentally relevant levels of arsenic promoted endothelial cell dysfunction and pathologic vascular remodeling. Increased angiogenesis, neovascularization, and inflammatory cell infiltration were observed in Matrigel plugs implanted in C57BL/6 mice following 5-week exposures to 5-500 ppb arsenic [Soucy, N.V., Mayka, D., Klei, L.R., Nemec, A.A., Bauer, J.A., Barchowsky, A., 2005. Neovascularization and angiogenic gene expression following chronic arsenic exposure in mice. Cardiovasc.Toxicol 5, 29-42]. Therefore, functional in vivo effects of arsenic on endothelial cell function and vessel remodeling in an endogenous vascular bed were investigated in the liver. Liver sinusoidal endothelial cells (LSEC) became progressively defenestrated and underwent capillarization to decrease vessel porosity following exposure to 250 ppb arsenic for 2 weeks. Sinusoidal expression of PECAM-1 and laminin-1 proteins, a hallmark of capillarization, was also increased by 2 weeks of exposure. LSEC caveolin-1 protein and caveolae expression were induced after 2 weeks of exposure indicating a compensatory change. Likewise, CD45/CD68-positive inflammatory cells did not accumulate in the livers until after LSEC porosity was decreased, indicating that inflammation is a consequence and not a cause of the arsenic-induced LSEC phenotype. The data demonstrate that the liver vasculature is an early target of pathogenic arsenic effects and that the mouse liver vasculature is a sensitive model for investigating vascular health effects of arsenic

  12. What is the best biomarker to assess arsenic exposure via drinking water?

    Science.gov (United States)

    Marchiset-Ferlay, Nathalie; Savanovitch, Chantal; Sauvant-Rochat, Marie-Pierre

    2012-02-01

    Arsenic (As) is a ubiquitous element. The current WHO guideline for As in drinking water is 10 μg/L. Furthermore, about 130 million people have only access to drinking water containing more than 10 g As/L. Although numerous studies have shown the related adverse effects of As, sensitive appropriate biomarkers are still required for studies of environmental epidemiology. A review of the literature has shown that various biomarkers are used for such research. Their limits and advantages are highlighted in this paper: (i) the detection of As or its derivatives in the blood is an indication of the dose ingested but it is not evidence of chronic intoxication. (ii) The detection of As in urine is an indispensible procedure because it is a good marker for internal dose. It has been demonstrated to correlate well for a number of chronic effects related to As levels in drinking water. However confounding factors must be taken into account to avoid misinterpretation and this may require As speciation. (iii) As in the hair and nails reflects the level of long term exposure but it is difficult to relate the level with the dose ingested. (iv) Some studies showed a correlation between urinary As and urinary and blood porphyrins. However, it is difficult to use only porphyrins as a biomarker in a population survey carried out without doing further studies. (v) Genotoxic effects are based on the characterization of these potential effects. Most studies have detected increases in DNA damage, sister chromatid exchange, micronuclei or chromosomal aberrations in populations exposed to As in drinking water. Micronuclei assay is the technique of choice to follow these populations, because it is sensitive and easy to use. To conclude, whatever epidemiological studies are, the urinary and toenail biomarkers are useful to provide indications of internal dose. Moreover, micronuclei assay can be complementary use as biomarker of early effects. Copyright © 2011 Elsevier Ltd. All rights

  13. Expression of the sFLT1 gene in cord blood cells is associated to maternal arsenic exposure and decreased birth weight.

    Directory of Open Access Journals (Sweden)

    Sylvie Remy

    Full Text Available There is increasing epidemiologic evidence that arsenic exposure in utero is associated with adverse pregnancy outcomes and may contribute to long-term health effects. These effects may occur at low environmental exposures but the underlying molecular mechanism is not clear. We collected cord blood samples of 183 newborns to identify associations between arsenic levels and birth anthropometric parameters in an area with very low arsenic exposure. Our core research aim was to screen for transcriptional marks that mechanistically explain these associations. Multiple regression analyses showed that birth weight decreased with 47 g (95% CI: 16-78 g for an interquartile range increase of 0.99 μg/L arsenic. The model was adjusted for child's sex, maternal smoking during pregnancy, gestational age, and parity. Higher arsenic concentrations and reduced birth weight were positively associated with changes in expression of the sFLT1 (soluble fms-like tyrosine kinase-1 gene in cord blood cells in girls. The protein product of sFLT1 is a scavenger of vascular endothelial growth factor (VEGF in the extracellular environment and plays a key role in the inhibition of placental angiogenesis. In terms of fetal development, inhibition of placental angiogenesis leads to impaired nutrition and hence to growth retardation. Various genes related to DNA methylation and oxidative stress showed also changed expression in relation to arsenic exposure but were not related to birth outcome parameters. In conclusion, this study suggests that increased expression of sFLT1 is an intermediate marker that points to placental angiogenesis as a pathway linking prenatal arsenic exposure to reduced birth weight.

  14. Arsenic pollution sources.

    Science.gov (United States)

    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

  15. Concentration and chemical status of arsenic in the blood of pregnant hamsters during critical embryogenesis. 1. Subchronic exposure to arsenate utilizing constant rate administration

    Energy Technology Data Exchange (ETDEWEB)

    Hanlon, D.P.; Ferm, V.H.

    1986-08-01

    The concentration, availability, and chemical status of radiolabeled arsenic has been determined in the blood of pregnant hamsters at the beginning (morning of Day 8) and the end (morning of Day 9) of the critical period of embryogenesis. Hamster dams were exposed to teratogenic doses of arsenate by means of osmotic minipumps implanted on the morning of Day 6 of the gestation period. Whole blood arsenic concentrations were the same for 48 and 72 hr postimplant. The arsenic concentration of plasma equaled that of red cells. Plasma arsenic was not bound to macromolecules and had the same chemical status 48 and 72 hr postimplant. Arsenate was the dominant form (67% of the total). However, the presence of dimethylarsinic acid and arsenite indicates that the pentavalent species was metabolized. Red cell arsenic was bound to macromolecules in the cell sap. Seventy percent of red cell sap arsenic was dialyzable 48 hr postimplant, but only 56% 72 hr postimplant. Arsenate was the dominant dialyzable red cell species on Day 8 and arsenite was the major dialyzable form on Day 9. The authors findings demonstrate a relationship between the maternal blood concentration and chemical status of arsenic and the presence of malformations resulting from a constant rate exposure of pregnant hamsters to arsenate via the osmotic minipump.

  16. Concentration and chemical status of arsenic in the blood of pregnant hamsters during critical embryogenesis. 1. Subchronic exposure to arsenate utilizing constant rate administration

    International Nuclear Information System (INIS)

    Hanlon, D.P.; Ferm, V.H.

    1986-01-01

    The concentration, availability, and chemical status of radiolabeled arsenic has been determined in the blood of pregnant hamsters at the beginning (morning of Day 8) and the end (morning of Day 9) of the critical period of embryogenesis. Hamster dams were exposed to teratogenic doses of arsenate by means of osmotic minipumps implanted on the morning of Day 6 of the gestation period. Whole blood arsenic concentrations were the same for 48 and 72 hr postimplant. The arsenic concentration of plasma equaled that of red cells. Plasma arsenic was not bound to macromolecules and had the same chemical status 48 and 72 hr postimplant. Arsenate was the dominant form (67% of the total). However, the presence of dimethylarsinic acid and arsenite indicates that the pentavalent species was metabolized. Red cell arsenic was bound to macromolecules in the cell sap. Seventy percent of red cell sap arsenic was dialyzable 48 hr postimplant, but only 56% 72 hr postimplant. Arsenate was the dominant dialyzable red cell species on Day 8 and arsenite was the major dialyzable form on Day 9. The authors findings demonstrate a relationship between the maternal blood concentration and chemical status of arsenic and the presence of malformations resulting from a constant rate exposure of pregnant hamsters to arsenate via the osmotic minipump

  17. Toxic Substances Portal- Arsenic

    Science.gov (United States)

    ... is found at low levels in breast milk. top How can families reduce their risk for exposure to arsenic? If you use arsenic-treated wood in home projects, you should wear dust masks, gloves, and protective clothing to decrease exposure to sawdust. ...

  18. Potential arsenic exposures in 25 species of zoo animals living in CCA-wood enclosures

    International Nuclear Information System (INIS)

    Gress, J.; Silva, E.B. da; Oliveira, L.M. de; Zhao, Di; Anderson, G.; Heard, D.; Stuchal, L.D.; Ma, L.Q.

    2016-01-01

    Animal enclosures are often constructed from wood treated with the pesticide chromated copper arsenate (CCA), which leaches arsenic (As) into adjacent soil during normal weathering. This study evaluated potential pathways of As exposure in 25 species of zoo animals living in CCA-wood enclosures. We analyzed As speciation in complete animal foods, dislodgeable As from CCA-wood, and As levels in enclosure soils, as well as As levels in biomarkers of 9 species of crocodilians (eggs), 4 species of birds (feathers), 1 primate species (hair), and 1 porcupine species (quills). Elevated soil As in samples from 17 enclosures was observed at 1.0–110 mg/kg, and enclosures housing threatened and endangered species had As levels higher than USEPA's risk-based Eco-SSL for birds and mammals of 43 and 46 mg/kg. Wipe samples of CCA-wood on which primates sit had dislodgeable As residues of 4.6–111 μg/100 cm 2 , typical of unsealed CCA-wood. Inorganic As doses from animal foods were estimated at 0.22–7.8 μg/kg bw/d. Some As levels in bird feathers and crocodilian eggs were higher than prior studies on wild species. However, hair from marmosets had 6.37 mg/kg As, 30-fold greater than the reference value, possibly due to their inability to methylate inorganic As. Our data suggested that elevated As in soils and dislodgeable As from CCA-wood could be important sources of As exposure for zoo animals. - Highlights: • Daily inorganic As dose from zoo animal foods was 0.22–7.8 μg/kg bw/day. • Total As concentrations in soils of zoo animal enclosures were 1.0–110 mg/kg. • Endangered zoo animals live in soils with As above USEPA Eco-SSLs for avian and mammal species. • Dislodgeable As on CCA-wood beams where primates sit was 4.6–111 μg/100 cm 2 . • Marmoset hair had 6.37 mg/kg As compared to a reference value of 0.21 mg/kg.

  19. Potential arsenic exposures in 25 species of zoo animals living in CCA-wood enclosures

    Energy Technology Data Exchange (ETDEWEB)

    Gress, J. [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Jiangsu 201146 (China); Soil and Water Science Department, University of Florida, Gainesville, FL 32611 (United States); Silva, E.B. da; Oliveira, L.M. de [Soil and Water Science Department, University of Florida, Gainesville, FL 32611 (United States); Zhao, Di [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Jiangsu 201146 (China); Anderson, G. [Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Heard, D. [Department of Small Animal Clinical Sciences, University of Florida, Gainesville, FL 32610 (United States); Stuchal, L.D. [Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32611 (United States); Ma, L.Q., E-mail: lqma@ufl.edu [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Jiangsu 201146 (China); Soil and Water Science Department, University of Florida, Gainesville, FL 32611 (United States)

    2016-05-01

    Animal enclosures are often constructed from wood treated with the pesticide chromated copper arsenate (CCA), which leaches arsenic (As) into adjacent soil during normal weathering. This study evaluated potential pathways of As exposure in 25 species of zoo animals living in CCA-wood enclosures. We analyzed As speciation in complete animal foods, dislodgeable As from CCA-wood, and As levels in enclosure soils, as well as As levels in biomarkers of 9 species of crocodilians (eggs), 4 species of birds (feathers), 1 primate species (hair), and 1 porcupine species (quills). Elevated soil As in samples from 17 enclosures was observed at 1.0–110 mg/kg, and enclosures housing threatened and endangered species had As levels higher than USEPA's risk-based Eco-SSL for birds and mammals of 43 and 46 mg/kg. Wipe samples of CCA-wood on which primates sit had dislodgeable As residues of 4.6–111 μg/100 cm{sup 2}, typical of unsealed CCA-wood. Inorganic As doses from animal foods were estimated at 0.22–7.8 μg/kg bw/d. Some As levels in bird feathers and crocodilian eggs were higher than prior studies on wild species. However, hair from marmosets had 6.37 mg/kg As, 30-fold greater than the reference value, possibly due to their inability to methylate inorganic As. Our data suggested that elevated As in soils and dislodgeable As from CCA-wood could be important sources of As exposure for zoo animals. - Highlights: • Daily inorganic As dose from zoo animal foods was 0.22–7.8 μg/kg bw/day. • Total As concentrations in soils of zoo animal enclosures were 1.0–110 mg/kg. • Endangered zoo animals live in soils with As above USEPA Eco-SSLs for avian and mammal species. • Dislodgeable As on CCA-wood beams where primates sit was 4.6–111 μg/100 cm{sup 2}. • Marmoset hair had 6.37 mg/kg As compared to a reference value of 0.21 mg/kg.

  20. Transplacental arsenic carcinogenesis in mice

    International Nuclear Information System (INIS)

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

    2007-01-01

    Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show 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

  1. Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures.

    Directory of Open Access Journals (Sweden)

    Cara L Sherwood

    Full Text Available Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE cell model we found that both micromolar (3.9 μM and submicromolar (0.8 μM arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-. We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway.

  2. Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cells vulnerable to arsenic-induced cell damage

    International Nuclear Information System (INIS)

    Yang, Bei; Fu, Jingqi; Zheng, Hongzhi; Xue, Peng; Yarborough, Kathy; Woods, Courtney G.; Hou, Yongyong; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2012-01-01

    Chronic human exposure to inorganic arsenic (iAs), a potent environmental oxidative stressor, is associated with increased prevalence of type 2 diabetes, where impairment of pancreatic β-cell function is a key pathogenic factor. Nuclear factor E2-related factor 2 (Nrf2) is a central transcription factor regulating cellular adaptive response to oxidative stress. However, persistent activation of Nrf2 in response to chronic oxidative stress, including inorganic arsenite (iAs 3+ ) exposure, blunts glucose-triggered reactive oxygen species (ROS) signaling and impairs glucose-stimulated insulin secretion (GSIS). In the current study, we found that MIN6 pancreatic β-cells with stable knockdown of Nrf2 (Nrf2-KD) by lentiviral shRNA and pancreatic islets isolated from Nrf2-knockout (Nrf2−/−) mice exhibited reduced expression of several antioxidant and detoxification enzymes in response to acute iAs 3+ exposure. As a result, Nrf2-KD MIN6 cells and Nrf2−/− islets were more susceptible to iAs 3+ and monomethylarsonous acid (MMA 3+ )-induced cell damage, as measured by decreased cell viability, augmented apoptosis and morphological change. Pretreatment of MIN6 cells with Nrf2 activator tert-butylhydroquinone protected the cells from iAs 3+ -induced cell damage in an Nrf2-dependent fashion. In contrast, antioxidant N‐acetyl cysteine protected Nrf2-KD MIN6 cells against acute cytotoxicity of iAs 3+ . The present study demonstrates that Nrf2-mediated antioxidant response is critical in the pancreatic β-cell defense mechanism against acute cytotoxicity by arsenic. The findings here, combined with our previous results on the inhibitory effect of antioxidants on ROS signaling and GSIS, suggest that Nrf2 plays paradoxical roles in pancreatic β-cell dysfunction induced by environmental arsenic exposure. -- Highlights: ► Lack of Nrf2 reduced expression of antioxidant genes induced by iAs 3+ in β-cells. ► Deficiency of Nrf2 in β-cells sensitized to iAs 3+ and MMA 3

  3. Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cells vulnerable to arsenic-induced cell damage

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Bei [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Department of Histology and Embryology, College of Basic Medical Sciences, China Medical University, Shenyang 110001 (China); Fu, Jingqi; Zheng, Hongzhi; Xue, Peng; Yarborough, Kathy; Woods, Courtney G.; Hou, Yongyong; Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2012-11-01

    Chronic human exposure to inorganic arsenic (iAs), a potent environmental oxidative stressor, is associated with increased prevalence of type 2 diabetes, where impairment of pancreatic β-cell function is a key pathogenic factor. Nuclear factor E2-related factor 2 (Nrf2) is a central transcription factor regulating cellular adaptive response to oxidative stress. However, persistent activation of Nrf2 in response to chronic oxidative stress, including inorganic arsenite (iAs{sup 3+}) exposure, blunts glucose-triggered reactive oxygen species (ROS) signaling and impairs glucose-stimulated insulin secretion (GSIS). In the current study, we found that MIN6 pancreatic β-cells with stable knockdown of Nrf2 (Nrf2-KD) by lentiviral shRNA and pancreatic islets isolated from Nrf2-knockout (Nrf2−/−) mice exhibited reduced expression of several antioxidant and detoxification enzymes in response to acute iAs{sup 3+} exposure. As a result, Nrf2-KD MIN6 cells and Nrf2−/− islets were more susceptible to iAs{sup 3+} and monomethylarsonous acid (MMA{sup 3+})-induced cell damage, as measured by decreased cell viability, augmented apoptosis and morphological change. Pretreatment of MIN6 cells with Nrf2 activator tert-butylhydroquinone protected the cells from iAs{sup 3+}-induced cell damage in an Nrf2-dependent fashion. In contrast, antioxidant N‐acetyl cysteine protected Nrf2-KD MIN6 cells against acute cytotoxicity of iAs{sup 3+}. The present study demonstrates that Nrf2-mediated antioxidant response is critical in the pancreatic β-cell defense mechanism against acute cytotoxicity by arsenic. The findings here, combined with our previous results on the inhibitory effect of antioxidants on ROS signaling and GSIS, suggest that Nrf2 plays paradoxical roles in pancreatic β-cell dysfunction induced by environmental arsenic exposure. -- Highlights: ► Lack of Nrf2 reduced expression of antioxidant genes induced by iAs{sup 3+} in β-cells. ► Deficiency of Nrf2 in

  4. MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice

    International Nuclear Information System (INIS)

    Kimura, Akihiko; Ishida, Yuko; Wada, Takashi; Yokoyama, Hitoshi; Mukaida, Naofumi; Kondo, Toshikazu

    2005-01-01

    To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs

  5. Arsenic and nicotine co-exposure lead to some synergistic effects on oxidative stress and apoptotic markers in young rat blood, liver, kidneys and brain

    Directory of Open Access Journals (Sweden)

    Anshu Jain

    2015-01-01

    Full Text Available Arsenic and nicotine exposure has been a major health concern globally. Individually both these toxicants increase the risk to various diseases including cancers. However, limited information exists on the co-exposure. In this study, we evaluate the effects of their individual and combined exposure and if co-exposure to these toxicants might have a synergism or antagonism. Male rats were exposed to a very low dose of arsenic (25 ppm in drinking water or nicotine (0.25 mg/kg, sub-cutaneously for a period of 5 months and post exposure various biochemical variables indicative of oxidative stress and apoptosis evaluated. Almost all glutathione linked enzymes showed marked alteration in individual as well as co-exposure treated groups. While serum creatinine and apoptosis indicator, lactate dehydrogenase (LDH were significantly increased in both treatments, an additive effect was noted in co-exposure group. A similar trend was also seen in brain and liver but not in kidneys. Gene expression studies showed marked reduction in catalase, Cu-Zn SOD, GST, there was a significant up regulation in Bax, caspase 3 in various tissues along with urinary 8-OHdG levels, indicative of DNA damage and apoptosis. Interestingly, a decrease in liver arsenic concentration was noted in co-exposed group compared to arsenic alone exposed group. In conclusion, the present study suggests that arsenic and nicotine exhibited significant toxicity during individual exposure whereas co-exposure to these toxins showed variable conditions (indicative of both synergism and antagonism in male rats.

  6. Estimating the risk of bladder and kidney cancer from exposure to low-levels of arsenic in drinking water, Nova Scotia, Canada.

    Science.gov (United States)

    Saint-Jacques, Nathalie; Brown, Patrick; Nauta, Laura; Boxall, James; Parker, Louise; Dummer, Trevor J B

    2018-01-01

    Arsenic in drinking water impacts health. Highest levels of arsenic have been historically observed in Taiwan and Bangladesh but the contaminant has been affecting the health of people globally. Strong associations have been confirmed between exposure to high-levels of arsenic in drinking water and a wide range of diseases, including cancer. However, at lower levels of exposure, especially near the current World Health Organization regulatory limit (10μg/L), this association is inconsistent as the effects are mostly extrapolated from high exposure studies. This ecological study used Bayesian inference to model the relative risk of bladder and kidney cancer at these lower concentrations-0-2μg/L; 2-5μg/L and; ≥5μg/L of arsenic-in 864 bladder and 525 kidney cancers diagnosed in the study area, Nova Scotia, Canada between 1998 and 2010. The model included proxy measures of lifestyle (e.g. smoking) and accounted for spatial dependencies. Overall, bladder cancer risk was 16% (2-5μg/L) and 18% (≥5μg/L) greater than that of the referent group (water arsenic-levels within the current the World Health Organization maximum acceptable concentration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Prenatal arsenic exposure and the epigenome: altered microRNAs associated with innate and adaptive immune signaling in newborn cord blood.

    Science.gov (United States)

    Rager, Julia E; Bailey, Kathryn A; Smeester, Lisa; Miller, Sloane K; Parker, Joel S; Laine, Jessica E; Drobná, Zuzana; Currier, Jenna; Douillet, Christelle; Olshan, Andrew F; Rubio-Andrade, Marisela; Stýblo, Miroslav; García-Vargas, Gonzalo; Fry, Rebecca C

    2014-04-01

    The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. Copyright © 2013 Wiley Periodicals, Inc.

  8. Phosphorus improves arsenic phytoremediation by Anadenanthera peregrina by alleviating induced oxidative stress.

    Science.gov (United States)

    Gomes, M P; Carvalho, M; Carvalho, G S; Marques, T C L L S M; Garcia, Q S; Guilherme, L R G; Soares, A M

    2013-01-01

    Due to similarities in their chemical behaviors, studies examining interactions between arsenic (As)--in special arsenate--and phosphorus (P) are important for better understanding arsenate uptake, toxicity, and accumulation in plants. We evaluated the effects of phosphate addition on plant biomass and on arsenate and phosphate uptake by Anadenanthera peregrina, an important Brazilian savanna legume. Plants were grown for 35 days in substrates that received combinations of 0, 10, 50, and 100 mg kg(-1) arsenate and 0, 200, and 400 mg kg(-1) phosphate. The addition of P increased the arsenic-phytoremediation capacity of A. peregrina by increasing As accumulation, while also alleviating As-induced oxidative stress. Arsenate phytotoxicity in A. peregrina is due to lipid peroxidation, but not hydrogen peroxide accumulation. Added P also increased the activity of important reactive oxygen species-scavenging enzymes (catalase and ascorbate peroxidase) that help prevent lipid peroxidation in leaves. Our findings suggest that applying P represents a feasible strategy for more efficient As phytoremediation using A. peregrina.

  9. PI3K/Akt/GSK3β induced CREB activation ameliorates arsenic mediated alterations in NMDA receptors and associated signaling in rat hippocampus: Neuroprotective role of curcumin.

    Science.gov (United States)

    Srivastava, Pranay; Dhuriya, Yogesh K; Kumar, Vivek; Srivastava, Akriti; Gupta, Richa; Shukla, Rajendra K; Yadav, Rajesh S; Dwivedi, Hari N; Pant, Aditya B; Khanna, Vinay K

    2018-04-30

    Protective efficacy of curcumin in arsenic induced NMDA receptor dysfunctions and PI3K/Akt/ GSK3β signalling in hippocampus has been investigated in vivo and in vitro. Exposure to sodium arsenite (in vivo - 20 mg/kg, body weight p.o. for 28 days; in vitro - 10 μM for 24 h) and curcumin (in vivo - 100 mg/kg body weight p.o. for 28 days; in vitro - 20 μM for 24 h) was carried out alone or simultaneously. Treatment with curcumin ameliorated sodium arsenite induced alterations in the levels of NMDA receptors, its receptor subunits and synaptic proteins - pCaMKIIα, PSD-95 and SynGAP both in vivo and in vitro. Decreased levels of BDNF, pAkt, pERK1/2, pGSK3β and pCREB on sodium arsenite exposure were also protected by curcumin. Curcumin was found to decrease sodium arsenite induced changes in hippocampus by modulating PI3K/Akt/GSK3β neuronal survival pathway, known to regulate various cellular events. Treatment of hippocampal cultures with pharmacological inhibitors for ERK1/2, GSK3β and Akt individually inhibited levels of CREB and proteins associated with PI3K/Akt/GSK3β pathway. Simultaneous treatment with curcumin was found to improve sodium arsenite induced learning and memory deficits in rats assessed by water maze and Y-maze. The results provide evidence that curcumin exercises its neuroprotective effect involving PI3K/Akt pathway which may affect NMDA receptors and downstream signalling through TrKβ and BDNF in arsenic induced cognitive deficits in hippocampus. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Exposure assessment of organochlorine pesticides, arsenic, and lead in children from the major agricultural areas in Sonora, Mexico.

    Science.gov (United States)

    Meza-Montenegro, Maria M; Valenzuela-Quintanar, Ana I; Balderas-Cortés, José J; Yañez-Estrada, Leticia; Gutiérrez-Coronado, Maria L; Cuevas-Robles, Alberto; Gandolfi, A Jay

    2013-04-01

    There is a lack of information of exposure to organochlorine pesticides (OCP) and some metals, such as lead (Pb) and arsenic (As), both of which were used as arsenicals pesticides, in children living in the major agricultural areas of Mexico. The objective of this study was to assess the exposure of children to different OCP, As, and Pb in the Yaqui and Mayo valleys of Sonora to generate population baseline levels of these toxins. A cross-sectional study was undertaken in 165 children (age 6-12 years old) from 10 communities from both valleys during 2009. Blood samples were analyzed for OCP and Pb and first morning void urine for inorganic As (InAs). All of the blood samples had detectable levels of dichlorodiphenyltrichloroethylene (p,p'-DDE) ranging from 0.25 to 10.3 μg/L. However lindane, dichlorodiphenyltrichloroethane (p,p'-DDT), aldrin, and endosulfan were detected in far less of the population (36.4, 23.6, 9.1, and 3 %, respectively). Methoxychlor and endrin were not found in any sample. The average value of Pb in this population was 3.2 μg Pb/dL (range 0.17-9.0) with 8.5 % of the samples having levels 50 μg/L were observed in 12.7 % of the samples. Our results show that is important to start a risk-reduction program to decrease exposure to these toxins in Mexican communities. In addition, the results can be used to establish the baseline levels of exposure to these toxins in this agricultural region and may be used as a reference point for regulatory agencies.

  11. [Arsenical keratosis treated by dermatome shaving].

    Science.gov (United States)

    Kjerkegaard, Ulrik Knap; Heje, Jens Martin; Vestergaard, Christian; Stausbøl-Grøn, Birgitte; Stolle, Lars Bjørn

    2014-05-05

    Cutaneous malignancy in association with arsenic exposure is a rare but well-documented phenomenon. Signs of chronic arsenic exposure are very rare in Denmark today. However, arsenic was used in the medical treatment of psoriasis vulgaris up till the 1980's and several patients suffer from this arsenic treatment today. This case report shows that arsenical keratosis can be treated by dermatome shaving, a superficial destructive therapy.

  12. Haematogical changes induced by subchronic glyphosate exposure ...

    African Journals Online (AJOL)

    The aim of this study was to determine the haematological changes induced by subchronic glyphosate exposure in Wistar rats and the ameliorative effect of zinc. Sixty adult male and female Wistar rats were used for the study. Twelve of them were used for the LD50 which was evaluated to be 3750 mg kg-1 with clinical ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China)

    2013-01-15

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  15. Association of arsenic, cadmium and manganese exposure with neurodevelopment and behavioural disorders in children: A systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Rodríguez-Barranco, Miguel; Lacasaña, Marina; Aguilar-Garduño, Clemente; Alguacil, Juan; Gil, Fernando; González-Alzaga, Beatriz; Rojas-García, Antonio

    2013-01-01

    The aim of this study was to analyse the scientific evidence published to date on the potential effects on neurodevelopment and behavioural disorders in children exposed to arsenic, cadmium and manganese and to quantify the magnitude of the effect on neurodevelopment by pooling the results of the different studies. We conducted a systematic review of original articles from January 2000 until March 2012, that evaluate the effects on neurodevelopment and behavioural disorders due to pre or post natal exposure to arsenic, cadmium and manganese in children up to 16 years of age. We also conducted a meta-analysis assessing the effects of exposure to arsenic and manganese on neurodevelopment. Forty-one articles that evaluated the effects of metallic elements on neurodevelopment and behavioural disorders met the inclusion criteria: 18 examined arsenic, 6 cadmium and 17 manganese. Most studies evaluating exposure to arsenic (13 of 18) and manganese (14 of 17) reported a significant negative effect on neurodevelopment and behavioural disorders. Only two studies that evaluated exposure to cadmium found an association with neurodevelopmental or behavioural disorders. The results of our meta-analysis suggest that a 50% increase of arsenic levels in urine would be associated with a 0.4 decrease in the intelligence quotient (IQ) of children aged 5–15 years. Moreover a 50% increase of manganese levels in hair would be associated with a decrease of 0.7 points in the IQ of children aged 6–13 years. There is evidence that relates arsenic and manganese exposure with neurodevelopmental problems in children, but there is little information on cadmium exposure. Few studies have evaluated behavioural disorders due to exposure to these compounds, and manganese is the only one for which there is more evidence of the existence of association with attention deficit disorder with hyperactivity. - Highlights: • We evaluated the association between As, Cd and Mn with neurodevelopment in

  16. Association of arsenic, cadmium and manganese exposure with neurodevelopment and behavioural disorders in children: A systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Rodríguez-Barranco, Miguel [Andalusian School of Public Health (EASP), Granada (Spain); Lacasaña, Marina, E-mail: marina.lacasana.easp@juntadeandalucia.es [Andalusian School of Public Health (EASP), Granada (Spain); CIBER of Epidemiology and Public Health (CIBERESP), Madrid (Spain); Aguilar-Garduño, Clemente [CIBER of Epidemiology and Public Health (CIBERESP), Madrid (Spain); Centre Superior d' Investigació en Salut Pública, Conselleria de Sanitat, Valencia (Spain); Alguacil, Juan [CIBER of Epidemiology and Public Health (CIBERESP), Madrid (Spain); Department of Environmental Biology and Public Health, University of Huelva, Huelva (Spain); Gil, Fernando [Department of Legal Medicine and Toxicology, University of Granada, Granada (Spain); González-Alzaga, Beatriz [Andalusian School of Public Health (EASP), Granada (Spain); Rojas-García, Antonio [CIBER of Epidemiology and Public Health (CIBERESP), Madrid (Spain)

    2013-06-01

    The aim of this study was to analyse the scientific evidence published to date on the potential effects on neurodevelopment and behavioural disorders in children exposed to arsenic, cadmium and manganese and to quantify the magnitude of the effect on neurodevelopment by pooling the results of the different studies. We conducted a systematic review of original articles from January 2000 until March 2012, that evaluate the effects on neurodevelopment and behavioural disorders due to pre or post natal exposure to arsenic, cadmium and manganese in children up to 16 years of age. We also conducted a meta-analysis assessing the effects of exposure to arsenic and manganese on neurodevelopment. Forty-one articles that evaluated the effects of metallic elements on neurodevelopment and behavioural disorders met the inclusion criteria: 18 examined arsenic, 6 cadmium and 17 manganese. Most studies evaluating exposure to arsenic (13 of 18) and manganese (14 of 17) reported a significant negative effect on neurodevelopment and behavioural disorders. Only two studies that evaluated exposure to cadmium found an association with neurodevelopmental or behavioural disorders. The results of our meta-analysis suggest that a 50% increase of arsenic levels in urine would be associated with a 0.4 decrease in the intelligence quotient (IQ) of children aged 5–15 years. Moreover a 50% increase of manganese levels in hair would be associated with a decrease of 0.7 points in the IQ of children aged 6–13 years. There is evidence that relates arsenic and manganese exposure with neurodevelopmental problems in children, but there is little information on cadmium exposure. Few studies have evaluated behavioural disorders due to exposure to these compounds, and manganese is the only one for which there is more evidence of the existence of association with attention deficit disorder with hyperactivity. - Highlights: • We evaluated the association between As, Cd and Mn with neurodevelopment in

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  18. Cardiovascular risk from water arsenic exposure in Vietnam: Application of systematic review and meta-regression analysis in chemical health risk assessment.

    Science.gov (United States)

    Phung, Dung; Connell, Des; Rutherford, Shannon; Chu, Cordia

    2017-06-01

    A systematic review (SR) and meta-analysis cannot provide the endpoint answer for a chemical risk assessment (CRA). The objective of this study was to apply SR and meta-regression (MR) analysis to address this limitation using a case study in cardiovascular risk from arsenic exposure in Vietnam. Published studies were searched from PubMed using the keywords of arsenic exposure and cardiovascular diseases (CVD). Random-effects meta-regression was applied to model the linear relationship between arsenic concentration in water and risk of CVD, and then the no-observable-adverse-effect level (NOAEL) were identified from the regression function. The probabilistic risk assessment (PRA) technique was applied to characterize risk of CVD due to arsenic exposure by estimating the overlapping coefficient between dose-response and exposure distribution curves. The risks were evaluated for groundwater, treated and drinking water. A total of 8 high quality studies for dose-response and 12 studies for exposure data were included for final analyses. The results of MR suggested a NOAEL of 50 μg/L and a guideline of 5 μg/L for arsenic in water which valued as a half of NOAEL and guidelines recommended from previous studies and authorities. The results of PRA indicated that the observed exposure level with exceeding CVD risk was 52% for groundwater, 24% for treated water, and 10% for drinking water in Vietnam, respectively. The study found that systematic review and meta-regression can be considered as an ideal method to chemical risk assessment due to its advantages to bring the answer for the endpoint question of a CRA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Quantification of arsenic in activated carbon using particle induced X-ray emission

    International Nuclear Information System (INIS)

    Yadav, Nirbhay N.; Maheswaran, Saravanamuthu; Shutthanandan, Vaithiyalingam; Thevuthasan, Suntharampillai; Ngo, Huu H.; Vigneswaran, Saravanamuth

    2006-01-01

    To date, the trace elemental analysis of solids with inhomogeneous internal structure has been limited, particularly in the case of adsorbents. High-energy ion beam based particle induced X-ray emission (PIXE) is an ideal analytical tool suitable for simultaneous quantification of trace elements with high accuracy. In this study, PIXE was used to quantify arsenic in the adsorbents, granular activated carbon (GAC) and powder activated carbon (PAC). Pelletized and unmodified GAC and PAC samples were analyzed along with powder samples deposited on thin teflon filters. These sample preparation methods resulted in samples of various thicknesses and densities. PIXE measurements taken from these samples were compared to results from neutron activation analysis (NAA) and atomic absorption spectroscopy (AAS). There is a good agreement between the values from the NAA and pelletized PIXE measurements and some AAS measurements

  20. Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh

    International Nuclear Information System (INIS)

    Huda, Nazmul; Hossain, Shakhawoat; Rahman, Mashiur; Karim, Md. Rezaul; Islam, Khairul; Mamun, Abdullah Al; Hossain, Md. Imam; Mohanto, Nayan Chandra; Alam, Shahnur; Aktar, Sharmin; Arefin, Afroza; Ali, Nurshad; Salam, Kazi Abdus; Aziz, Abdul; Saud, Zahangir Alam; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2014-01-01

    Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with

  1. Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Huda, Nazmul [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Department of Medicine, Rajshahi Medical College, Rajshahi 6000 (Bangladesh); Hossain, Shakhawoat; Rahman, Mashiur [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Karim, Md. Rezaul [Department of Applied Nutrition and Food Technology, Islamic University, Kushtia 7003 (Bangladesh); Islam, Khairul [Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Santosh, Tangail 1902 (Bangladesh); Mamun, Abdullah Al; Hossain, Md. Imam; Mohanto, Nayan Chandra; Alam, Shahnur; Aktar, Sharmin; Arefin, Afroza; Ali, Nurshad; Salam, Kazi Abdus; Aziz, Abdul; Saud, Zahangir Alam [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Miyataka, Hideki; Himeno, Seiichiro [Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514 (Japan); Hossain, Khaled, E-mail: khossainbio@gmail.com [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh)

    2014-11-15

    Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with

  2. Assessing Health Risk due to Exposure to Arsenic in Drinking Water in Hanam Province, Vietnam

    Directory of Open Access Journals (Sweden)

    Tung Bui Huy

    2014-07-01

    Full Text Available We assessed health risks related to Arsenic (As in contaminated drinking water in Hanam, applying the Australian Environmental Health Risk Assessment Framework, which promotes stakeholder involvement in risk assessments. As concentrations in 300 tube-well water samples, before and after filtration, were analyzed and the water consumption levels in 150 households were estimated. Skin cancer risk was characterized using Cancer Slope Factor index and lifetime average daily dose with a probabilistic approach. The results showed that arsenic concentrations in tube-well water ranged from 8–579 ppb (mean 301 ppb before filtration and current sand filters used by the households did not meet the standard for As removal. Arsenic daily consumption of 40% of the adults exceeded the level of TDI (Tolerable Daily Intake at 1 µg/kg/day. The average skin cancer risk in adults due to consuming filtered tube-well water for drinking purpose were 25.3 × 10−5 (using only well water and 7.6 × 10−5 (using both well and rain water. The skin cancer risk would be 11.5 times higher if the water was not filtered. Improvement of filtration measures or the replacement of the current drinking water sources to minimize the health risks to the local population is urgently needed.

  3. Assessing Health Risk due to Exposure to Arsenic in Drinking Water in Hanam Province, Vietnam

    Science.gov (United States)

    Bui Huy, Tung; Tuyet-Hanh, Tran Thi; Johnston, Richard; Nguyen-Viet, Hung

    2014-01-01

    We assessed health risks related to Arsenic (As) in contaminated drinking water in Hanam, applying the Australian Environmental Health Risk Assessment Framework, which promotes stakeholder involvement in risk assessments. As concentrations in 300 tube-well water samples, before and after filtration, were analyzed and the water consumption levels in 150 households were estimated. Skin cancer risk was characterized using Cancer Slope Factor index and lifetime average daily dose with a probabilistic approach. The results showed that arsenic concentrations in tube-well water ranged from 8–579 ppb (mean 301 ppb) before filtration and current sand filters used by the households did not meet the standard for As removal. Arsenic daily consumption of 40% of the adults exceeded the level of TDI (Tolerable Daily Intake) at 1 µg/kg/day. The average skin cancer risk in adults due to consuming filtered tube-well water for drinking purpose were 25.3 × 10−5 (using only well water) and 7.6 × 10−5 (using both well and rain water). The skin cancer risk would be 11.5 times higher if the water was not filtered. Improvement of filtration measures or the replacement of the current drinking water sources to minimize the health risks to the local population is urgently needed. PMID:25062276

  4. Public health risk assessment associated with heavy metal and arsenic exposure near an abandoned mine (Kirki, Greece).

    Science.gov (United States)

    Nikolaidis, Christos; Orfanidis, Moysis; Hauri, Dimitri; Mylonas, Stratos; Constantinidis, Theodore

    2013-12-01

    The 'Agios Philippos' lead-zinc mine in the Kirki region (NE Greece) is now closed, but its legacy of heavy metal contamination remains at the site. At present, management of the contaminated land is of major concern. The area is in a reclamation process and requires immediate remediation action, whereas human risks need to be carefully evaluated. In order to assess these risks, samples from around the mine were collected and analyzed and a scenario involving the oral, dermal, and inhaled doses of arsenic and heavy metals was formulated. A Monte Carlo approach was undertaken, in order to model the average daily dose and quantify the corresponding hazard index and cancer risk. A toxicological risk was associated with samples collected in the vicinity of the mine (floatation, mine tailings) and a pronounced carcinogenic risk for arsenic was evident at the broader occupational/environmental setting. These findings urge for immediate rehabilitation actions that will mitigate population exposures and promote long-term environmental safety in the area.

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

    Science.gov (United States)

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

    2015-08-01

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

  6. Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic-induced toxicity in mice

    Directory of Open Access Journals (Sweden)

    Guha B

    2003-10-01

    Full Text Available Abstract Background Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols. Methods Mice were divided into different sets of control (both positive and negative and treated series (As-intoxicated, As-intoxicated plus drug-fed. Alanine amino transferase (ALT and aspartate amino transferase (AST activities and reduced glutathione (GSH level in liver and blood were analyzed in the different series of mice at six different fixation intervals. Results Both Arsenicum Album-30 and Arsenicum Album-200 ameliorated arsenic-induced toxicity to a considerable extent as compared to various controls. Conclusions The results lend further support to our earlier views that microdoses of potentized Arsenicum Album are capable of combating arsenic intoxication in mice, and thus are strong candidates for possible use in human subjects in arsenic contaminated areas under medical supervision.

  7. Arsenic is associated with reduced effect of folic acid in myelomeningocele prevention: a case control study in Bangladesh

    Science.gov (United States)

    Background: Arsenic induces neural tube defects in several animal models, but its potential to cause neural tube defects in humans is unknown. Our objective was to investigate the associations between maternal arsenic exposure, periconceptional folic acid supplementation, and risk of posterior neura...

  8. Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor

    International Nuclear Information System (INIS)

    Monzen, Hajime; Griffin, R.J.; Williams, B.W.; Amamo, Morikazu; Ando, Satoshi; Hasegawa, Takeo

    2004-01-01

    Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy. We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging (MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H and E) staining. Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an intraperitoneal (i.p.) injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days. The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor. (author)

  9. Education, fish consumption, well water, chicken coops, and cooking fires: Using biogeochemistry and ethnography to study exposure of children from Yucatan, Mexico to metals and arsenic

    International Nuclear Information System (INIS)

    Arcega-Cabrera, Flor; Fargher, Lane F.

    2016-01-01

    Around the world, the nocuous health effects of exposure to environmental contaminants, especially metals and Arsenic, are a growing health concern. This is especially the case in Mexico, where corruption and ineffective political administration are contributing to increasing deterioration in the environment. Importantly, shallow soils and the karstic nature of bedrock in Yucatan, Mexico make the subterranean aquifer especially susceptible to contamination because contaminates are carried to it with little resistance. Given these environmental conditions, we developed a multi/interdisciplinary project to evaluate the impact of metal and Arsenic pollution on a sample of 107 children, ages 6 to 9 years, living in the urban areas of Progreso, Merida, and Ticul, in the State of Yucatan using urine and blood samples. In addition, ethnographic research was carried out in the homes of the children that participated in the study to identify potential exposure pathways. This research proved invaluable because the complexity of human social organization, lifestyles, and geographical patterning create an intricate array of exposure pathways that vary across social sectors and geographic space. In the following article, we use nonparametric univariate statistical analysis to reveal potential exposure pathways among sub-populations included in our sample. These analyses show that children from poor/marginal families tend to be exposed to Copper, Lead, and Nickel; whereas, children, from wealthier families, tend to be exposed to Cadmium, Arsenic, and inorganic Copper (Copper Sulfate). - Highlights: • Metals and Arsenic exposure in children (age 6–9) from Yucatan, Mexico • Quantification of As, Cd, Hg, Pb, Cr, Cu, Ni in Blood and Urine by AAS • Ethnographic research on sociocultural patterns and exposure pathways • Non-parametric statistical analysis • Variation in exposure based on geography, socioeconomic level, and lifestyles

  10. Education, fish consumption, well water, chicken coops, and cooking fires: Using biogeochemistry and ethnography to study exposure of children from Yucatan, Mexico to metals and arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Arcega-Cabrera, Flor [Unidad de Química Sisal, Facultad de Química, Universidad Nacional Autónoma de México (Mexico); Fargher, Lane F., E-mail: fargher@mda.cinvestav.mx [Departamento de Ecología Humana, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional — Unidad Mérida (Mexico)

    2016-10-15

    Around the world, the nocuous health effects of exposure to environmental contaminants, especially metals and Arsenic, are a growing health concern. This is especially the case in Mexico, where corruption and ineffective political administration are contributing to increasing deterioration in the environment. Importantly, shallow soils and the karstic nature of bedrock in Yucatan, Mexico make the subterranean aquifer especially susceptible to contamination because contaminates are carried to it with little resistance. Given these environmental conditions, we developed a multi/interdisciplinary project to evaluate the impact of metal and Arsenic pollution on a sample of 107 children, ages 6 to 9 years, living in the urban areas of Progreso, Merida, and Ticul, in the State of Yucatan using urine and blood samples. In addition, ethnographic research was carried out in the homes of the children that participated in the study to identify potential exposure pathways. This research proved invaluable because the complexity of human social organization, lifestyles, and geographical patterning create an intricate array of exposure pathways that vary across social sectors and geographic space. In the following article, we use nonparametric univariate statistical analysis to reveal potential exposure pathways among sub-populations included in our sample. These analyses show that children from poor/marginal families tend to be exposed to Copper, Lead, and Nickel; whereas, children, from wealthier families, tend to be exposed to Cadmium, Arsenic, and inorganic Copper (Copper Sulfate). - Highlights: • Metals and Arsenic exposure in children (age 6–9) from Yucatan, Mexico • Quantification of As, Cd, Hg, Pb, Cr, Cu, Ni in Blood and Urine by AAS • Ethnographic research on sociocultural patterns and exposure pathways • Non-parametric statistical analysis • Variation in exposure based on geography, socioeconomic level, and lifestyles.

  11. Does airborne nickel exposure induce nickel sensitization?

    Science.gov (United States)

    Mann, Eugen; Ranft, Ulrich; Eberwein, Georg; Gladtke, Dieter; Sugiri, Dorothee; Behrendt, Heidrun; Ring, Johannes; Schäfer, Torsten; Begerow, Jutta; Wittsiepe, Jürgen; Krämer, Ursula; Wilhelm, Michael

    2010-06-01

    Nickel is one of the most prevalent causes of contact allergy in the general population. This study focuses on human exposure to airborne nickel and its potential to induce allergic sensitization. The study group consisted of 309 children at school-starter age living in the West of Germany in the vicinity of two industrial sources and in a rural town without nearby point sources of nickel. An exposure assessment of nickel in ambient air was available for children in the Ruhr district using routinely monitored ambient air quality data and dispersion modelling. Internal nickel exposure was assessed by nickel concentrations in morning urine samples of the children. The observed nickel sensitization prevalence rates varied between 12.6% and 30.7%. Statistically significant associations were showed between exposure to nickel in ambient air and urinary nickel concentration as well as between urinary nickel concentration and nickel sensitization. Furthermore, an elevated prevalence of nickel sensitization was associated with exposure to increased nickel concentrations in ambient air. The observed associations support the assumption that inhaled nickel in ambient air might be a risk factor for nickel sensitization; further studies in larger collectives are necessary.

  12. Arsenic trioxide mediates HAPI microglia inflammatory response and subsequent neuron apoptosis through p38/JNK MAPK/STAT3 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Mao, Jiamin [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Yang, Jianbing [Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001 (China); Zhang, Yan [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Li, Ting [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wang, Cheng [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Xu, Lingfei; Hu, Qiaoyun; Wang, Xiaoke; Jiang, Shengyang [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Nie, Xiaoke [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Chen, Gang, E-mail: chengang@ntu.edu.cn [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)

    2016-07-15

    Arsenic is a widely distributed toxic metalloid all over the world. Inorganic arsenic species are supposed to affect astrocytic functions and to cause neuron apoptosis in CNS. Microglias are the key cell type involved in innate immune responses in CNS, and microglia activation has been linked to inflammation and neurotoxicity. In this study, using ELISA, we showed that Arsenic trioxide up-regulated the expression and secretion of IL-1β in a dose-dependent manner and a time-dependent manner in cultured HAPI microglia cells. The secretion of IL-1β caused the apoptosis of SH-SY5Y. These pro-inflammatory responses were inhibited by the STAT3 blocker, AG490 and P38/JNK MAPK blockers SB202190, SP600125. Further, Arsenic trioxide exposure could induce phosphorylation and activation of STAT3, and the translocation of STAT3 from the cytosol to the nucleus in this HAPI microglia cell line. Thus, the STAT3 signaling pathway can be activated after Arsenic trioxide treatment. However, P38/JNK MAPK blockers SB202190, SP600125 also obviously attenuated STAT3 activation and transnuclear transport induced by Arsenic trioxide. In concert with these results, we highlighted that the secretion of IL-1β and STAT3 activation induced by Arsenic trioxide can be mediated by elevation of P38/JNK MAPK in HAPI microglia cells and then induced the toxicity of neurons. - Highlights: • Arsenic trioxide exposure induced expression of IL-β in HAPI microglia. • Arsenic trioxide exposure induced activation of MAPK pathways in HAPI microglia. • Arsenic trioxide exposure induced activation of STAT3 pathways in HAPI microglia. • The expression of IL-β though P38/JNK MAPK/STAT3 pathways in HAPI microglia.

  13. Arsenic trioxide mediates HAPI microglia inflammatory response and subsequent neuron apoptosis through p38/JNK MAPK/STAT3 pathway

    International Nuclear Information System (INIS)

    Mao, Jiamin; Yang, Jianbing; Zhang, Yan; Li, Ting; Wang, Cheng; Xu, Lingfei; Hu, Qiaoyun; Wang, Xiaoke; Jiang, Shengyang; Nie, Xiaoke; Chen, Gang

    2016-01-01

    Arsenic is a widely distributed toxic metalloid all over the world. Inorganic arsenic species are supposed to affect astrocytic functions and to cause neuron apoptosis in CNS. Microglias are the key cell type involved in innate immune responses in CNS, and microglia activation has been linked to inflammation and neurotoxicity. In this study, using ELISA, we showed that Arsenic trioxide up-regulated the expression and secretion of IL-1β in a dose-dependent manner and a time-dependent manner in cultured HAPI microglia cells. The secretion of IL-1β caused the apoptosis of SH-SY5Y. These pro-inflammatory responses were inhibited by the STAT3 blocker, AG490 and P38/JNK MAPK blockers SB202190, SP600125. Further, Arsenic trioxide exposure could induce phosphorylation and activation of STAT3, and the translocation of STAT3 from the cytosol to the nucleus in this HAPI microglia cell line. Thus, the STAT3 signaling pathway can be activated after Arsenic trioxide treatment. However, P38/JNK MAPK blockers SB202190, SP600125 also obviously attenuated STAT3 activation and transnuclear transport induced by Arsenic trioxide. In concert with these results, we highlighted that the secretion of IL-1β and STAT3 activation induced by Arsenic trioxide can be mediated by elevation of P38/JNK MAPK in HAPI microglia cells and then induced the toxicity of neurons. - Highlights: • Arsenic trioxide exposure induced expression of IL-β in HAPI microglia. • Arsenic trioxide exposure induced activation of MAPK pathways in HAPI microglia. • Arsenic trioxide exposure induced activation of STAT3 pathways in HAPI microglia. • The expression of IL-β though P38/JNK MAPK/STAT3 pathways in HAPI microglia.

  14. Arsenic trioxide induced rhabdomyolysis, a rare but severe side effect, in an APL patient: a case report.

    Science.gov (United States)

    He, Haiyan; An, Ran; Hou, Jian; Fu, Weijun

    2017-06-01

    Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined with all-trans-retinotic acid (ATRA), ATO has become the first-line induction therapy in treating acute promyelocytic leukemia (APL). The most common side effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium retention, and nervous system damage. In this report, we present a rare side effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with ATO. After taking 10 mg ATO daily for 6 days, she presented shortness of breath, myodynia, elevated creatine kinase, and acute renal insufficiency. This report describes the first case of ATO-induced rhabdomyolysis.

  15. Maternal arsenic exposure and birth outcomes: a comprehensive review of the epidemiologic literature focused on drinking water.

    Science.gov (United States)

    Bloom, Michael S; Surdu, Simona; Neamtiu, Iulia A; Gurzau, Eugen S

    2014-09-01

    Inorganic arsenic (iAs) is a human toxicant to which populations may be exposed through consumption of geogenically contaminated groundwater. A growing body of experimental literature corroborates the reproductive toxicity of iAs; however, the results of human studies are inconsistent. Therefore, we conducted a comprehensive review of epidemiologic studies focused on drinking water iAs exposure and birth outcomes to assess the evidence for causality and to make recommendations for future study. We reviewed 18 English language papers assessing birth weight, gestational age, and birth size. Thirteen of the studies were conducted among populations with frequent exposure to high-level groundwater iAs contamination (>10 μg/L) and five studies were conducted in areas without recognized contamination. Most studies comprised small samples and used cross-sectional designs, often with ecologic exposure assessment strategies, although several large prospective investigations and studies with individual-level measurements were also reported. We conclude that: (1) the epidemiologic evidence for an increased risk of low birth weight (water iAs contamination quality epidemiologic studies are necessary to more definitively assess the risk. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. ARSENIC-INDUCED SKIN CONDITIONS IDENTIFIED IN SOUTHWEST DERMATOLOGY PRACTICE: AN EPIDEMIOLOGIC TOOL?

    Science.gov (United States)

    Populations living in the Southwest United States are more likely to be exposed to elevated drinking water arsenic levels compared to other areas of the country. Skin changes, including hyperpigmentation and generalized hyperkeratosis, are the most common signs of chronic arsenic...

  17. Detection of trace amount of arsenic in groundwater by laser-induced breakdown spectroscopy and adsorption

    Science.gov (United States)

    Haider, A. F. M. Y.; Hedayet Ullah, M.; Khan, Z. H.; Kabir, Firoza; Abedin, K. M.

    2014-03-01

    LIBS technique coupled with adsorption has been applied for the efficient detection of arsenic in liquid. Several adsorbents like tea leaves, bamboo slice, charcoal and zinc oxide have been used to enable sensitive detection of arsenic presence in water using LIBS. Among these, zinc oxide and charcoal show the better results. The detection limits for arsenic in water were 1 ppm and 8 ppm, respectively, when ZnO and charcoal were used as adsorbents of arsenic. To date, the determination of 1 ppm of As in water is the lowest concentration of detected arsenic in water by the LIBS technique. The detection limit of As was lowered to even less than 100 ppb by a combination of LIBS technique, adsorption by ZnO and concentration enhancement technique. Using the combination of these three techniques the ultimate concentration of arsenic was found to be 0.083 ppm (83 ppb) for arsenic polluted water collected from a tube-well of Farajikandi union (longitude 90.64°, latitude 23.338° north) of Matlab Upozila of Chandpur district in Bangladesh. This result compares fairly well with the finding of arsenic concentration of 0.078 ppm in the sample by the AAS technique at the Bangladesh Council of Scientific and Industrial Research (BCSIR) lab. Such a low detection limit (1 ppm) of trace elements in liquid matrix has significantly enhanced the scope of LIBS as an analytical tool.

  18. Dietary exposure assessment for arsenic and mercury following submarine tailings placement in Ratatotok Sub-district, North Sulawesi, Indonesia

    International Nuclear Information System (INIS)

    Bentley, Keith; Soebandrio, Amin

    2017-01-01

    The Mesel gold mine in the Ratatotok Sub-district operated between 1996 and 2004 with tailings disposal via an engineered submarine tailings placement (STP) into Buyat Bay. This operation raised concerns of increased levels of arsenic (As) and mercury (Hg) associated disease in the local communities from consumption of seafood contaminated with anthropogenic As and Hg. This report uses the dietary exposure to As and Hg, from local fishermen and market-purchased Codex “as consumed” and environmental fish results from the pre-mining baseline (1990–1995), the mine operational (1996–2004) and post-closure monitoring (2007–2016) to examine the potential health effects. The Ratatotok Sub-district consumers total As average daily intake from fish was between 152 and 317 μg/day (adults) and 58 and 105 μg/day (infants). The average daily intake of inorganic arsenic (As i ) from the dietary staples fish and rice and drinking water consumption was 77 μg/day (adults) and 35 μg/day (infants) at Buyat Pantai and 39 μg/day (adults) and 19 μg/day (infants) at Ratatotok township. Fish consumption contributed 8.2% (adults) and 6.5% (infants) to total daily As i intake. Average Hg intake from fish consumption, exceeded the FAO WHO PTWI for methylmercury (MeHg) for all age and gender groups at Buyat Pantai 4.6 μg/kg bw/wk (adults) and 7.3 μg/kg bw/wk (infants) and for the infants at Buyat village and Ratatotok township (2.5 and 2.8 μg/kg bw/wk respectively). The Manado City consumers had average intakes below the MeHg PTWI. The Hg exceedances resulted from the high fish consumption in coastal communities and not elevated levels of Hg in fish. Hg exposure levels from the pre-mining baseline, Mesel STP operation and post-closure monitoring, confirmed that exceedances were unrelated to the tailings deposited into Buyat Bay. - Highlights: • Submarine tailings placement has not resulted in As and Hg associated disease. • Dietary exposures were unaffected

  19. Arsenic induces cell apoptosis in cultured osteoblasts through endoplasmic reticulum stress

    International Nuclear Information System (INIS)

    Tang, C.-H.; Chiu, Y.-C.; Huang, C.-F.; Chen, Y.-W.; Chen, P.-C.

    2009-01-01

    Osteoporosis is characterized by low bone mass resulting from an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Therefore, decreased bone formation by osteoblasts may lead to the development of osteoporosis, and rate of apoptosis is responsible for the regulation of bone formation. Arsenic (As) exists ubiquitously in our environment and increases the risk of neurotoxicity, liver injury, peripheral vascular disease and cancer. However, the effect of As on apoptosis of ost