Arsenic-contaminated Drinking Water Research Articles

Biotransformation of arsenite and bacterial aox activity in drinking water produced from surface water of floating houses: Arsenic contamination in Cambodia

The potential arsenite bioteansformation activity of arsenic was investigated by examining bacterial arsenic arsenite-oxidizing gene such as aoxS, aoxR, aoxA, aoxB, aoxC, and aoxD in high arsenic-contaminated drinking water produced from the surface water of floating houses. There is a biogeochemical cycle of activity involving arsenite oxidase aox system and the ars (arsenic resistance system) gene operon and aoxR leader gene activity in Alcaligenes faecalis SRR-11 and aoxS leader gene activity in Achromobacter xylosoxidans TSL-66. Batch experiments showed that SRR-11 and TSL-66 completely oxidized 1 mM of As (III) to As (V) within 35–40 h. The leaders of aoxS and aoxR are important for gene activity, and their effects in arsenic bioremediation and mobility in natural water has a significant ecological role because it allows arsenite oxidase in bacteria to control the biogeochemical cycle of arsenic-contaminated drinking water produced from surface water of floating houses.

Consumption of arsenic-contaminated drinking water and anemia among pregnant and non-pregnant women in northwestern Romania

Anemia is a global health problem. To evaluate the impact of low-moderate water arsenic exposure (mostly <10µg/L) on anemia, we conducted a cross-sectional study of 217 Romanian women. The adjusted prevalences for ‘any’ anemia (prevalence proportion ratio (PPR)=1.71, 95% CI 0.75–3.88) and pregnancy anemia (PPR=2.87, 95% CI 0.62–13.26) were higher among drinking water arsenic exposed women than among unexposed women. These preliminary data underscore the need for a more definitive study in this area.

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

BackgroundConsumption of arsenic-contaminated drinking water adversely affects health. There is interindividual variation in arsenic metabolism efficiency, partially due to genetic variation in the arsenic methyltransferase (AS3MT) gene region.ObjectivesThe goal of this study was to assess the overall contribution of genetic factors to variation in arsenic metabolism efficiency, as measured by the relative concentration of dimethylarsinic acid (DMA%) in urine.MethodsUsing data on genome-wide single nucleotide polymorphisms (SNPs) and urinary DMA% for 2,053 arsenic-exposed Bangladeshi individuals, we employed various SNP-based approaches for heritability estimation and polygenic modeling.ResultsUsing data on all participants, the percent variance explained (PVE) for DMA% by all measured and imputed SNPs was 16% (p = 0.08), which was reduced to 5% (p = 0.34) after adjusting for AS3MT SNPs. Using information on close relatives only, the PVE was 63% (p = 0.0002), but decreased to 41% (p = 0.01) after adjusting for AS3MT SNPs. Regional heritability analysis confirmed 10q24.32 (AS3MT) as a major arsenic metabolism locus (PVE = 7%, p = 4.4 × 10–10), but revealed no additional regions. We observed a moderate association between a polygenic score reflecting elevated DMA% (composed of thousands of non-AS3MT SNPs) and reduced skin lesion risk in an independent sample (p < 0.05). We observed no associations for SNPs reported in prior candidate gene studies of arsenic metabolism.ConclusionsOur results suggest that there are common variants outside of the AS3MT region that influence arsenic metabolism in Bangladeshi individuals, but the effects of these variants are very weak compared with variants near AS3MT. The high heritability estimates observed using family-based heritability approaches suggest substantial effects for rare variants and/or unmeasured environmental factors.CitationGao J, Tong L, Argos M, Scannell Bryan M, Ahmed A, Rakibuz-Zaman M, Kibriya MG, Jasmine F, Slavkovich V, Graziano JH, Ahsan H, Pierce BL. 2015. The genetic architecture of arsenic metabolism efficiency: a SNP-based heritability study of Bangladeshi adults. Environ Health Perspect 123:985–992; http://dx.doi.org/10.1289/ehp.1408909

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

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.

The health effects of exposure to arsenic-contaminated drinking water: a review by global geographical distribution

Chronic arsenic exposure through drinking water has been a vigorously studied and debated subject. However, the existing literature does not allow for a thorough examination of the potential regional discrepancies that may arise among arsenic-related health outcomes. The purpose of this article is to provide an updated review of the literature on arsenic exposure and commonly discussed health effects according to global geographical distribution. This geographically segmented approach helps uncover the discrepancies in the health effects of arsenic. For instance, women are more susceptible than men to a few types of cancer in Taiwan, but not in other countries. Although skin cancer and arsenic exposure correlations have been discovered in Chile, Argentina, the United States, and Taiwan, no evident association was found in mainland China. We then propose several globally applicable recommendations to prevent and treat the further spread of arsenic poisoning and suggestions of future study designs and decision-making.

Arsenic induces sustained impairment of skeletal muscle and muscle progenitor cell ultrastructure and bioenergetics

Over 4 million individuals in the United States, and over 140 million individuals worldwide, are exposed daily to arsenic-contaminated drinking water. Human exposures can range from below the current limit of 10μg/L to over 1mg/L, with 100μg/L promoting disease in a large portion of those exposed. Although increased attention has recently been paid to myopathy following arsenic exposure, the pathogenic mechanisms underlying clinical symptoms remain poorly understood. This study tested the hypothesis that arsenic induces lasting muscle mitochondrial dysfunction and impairs metabolism. Compared to nonexposed controls, mice exposed to drinking water containing 100μg/L arsenite for 5 weeks demonstrated impaired muscle function, mitochondrial myopathy, and altered oxygen consumption that were concomitant with increased mitochondrial fusion gene transcription. There were no differences in the levels of inorganic arsenic or its monomethyl and dimethyl metabolites between controls and exposed muscles, confirming that arsenic does not accumulate in muscle. Nevertheless, muscle progenitor cells isolated from exposed mice recapitulated the aberrant myofiber phenotype and were more resistant to oxidative stress, generated more reactive oxygen species, and displayed autophagic mitochondrial morphology, compared to cells isolated from nonexposed mice. These pathological changes from a possible maladaptive oxidative stress response provide insight into declines in muscle functioning caused by exposure to this common environmental contaminant.

Genotoxic and epigenetic mechanisms in arsenic carcinogenicity

Arsenic is a human carcinogen with weak mutagenic properties that induces tumors through mechanisms not yet completely understood. People worldwide are exposed to arsenic-contaminated drinking water, and epidemiological studies showed a high percentage of lung, bladder, liver, and kidney cancer in these populations. Several mechanisms by which arsenical compounds induce tumorigenesis were proposed including genotoxic damage and chromosomal abnormalities. Over the past decade, a growing body of evidence indicated that epigenetic modifications have a role in arsenic-inducing adverse effects on human health. The main epigenetic mechanisms are DNA methylation in gene promoter regions that regulate gene expression, histone tail modifications that regulate the accessibility of transcriptional machinery to genes, and microRNA activity (noncoding RNA able to modulate mRNA translation). The "double capacity" of arsenic to induce mutations and epimutations could be the main cause of arsenic-induced carcinogenesis. The aim of this review is to better clarify the mechanisms of the initiation and/or the promotion of arsenic-induced carcinogenesis in order to understand the best way to perform an early diagnosis and a prompt prevention that is the key point for protecting arsenic-exposed population. Studies on arsenic-exposed population should be designed in order to examine more comprehensively the presence and consequences of these genetic/epigenetic alterations.

Investigating arsenic (As) occurrence and sources in ground, surface, waste and drinking water in northern Mongolia

Elevated levels of arsenic in drinking water are found in several parts of Asia. Prolonged intakes of even low concentrations typically have serious health effects. This research paper integrates results of various studies on arsenic contamination of ground, surface, waste and drinking water in north-central Mongolia. Samples were analyzed with the ARSOlux biosensor and the Arsenator field test kit as well as different spectrometric methods (ICP-MS, ICP-OES). Altogether 309 samples were tested for their arsenic concentration, 44 of them with more than one technique. In the study region, the enrichment of heavy metals in surface waters is often linked to mining and coal combustion. The highest concentration of arsenic (As) was detected in the effluent of a gold mine (up to 2,820 μg L−1) and in the ash basin of a thermal power plant (up to 1,170 μg L−1). Five of 54 drinking water samples and 16 of 184 river samples were found to contain As levels above the World Health Organization (WHO) maximum permissible limit (10 μg L−1), with a maximum of 300 μg L−1 As. In addition, elevated levels of uranium were detected. The degree and extent of As concentrations exceeding WHO standards were previously unknown and demonstrate the necessity for a more intensive screening as well as possible interventions concerning the intake of arsenic-contaminated drinking water. Preliminary results indicate that the ARSOlux biosensor technology is well suited for a precise quantification of arsenic content at low detection limits in regions where access to central laboratories is difficult.

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

Background: Arsenic is a ubiquitous toxic element and is known to contaminate drinking water in many countries. Several epidemiological studies have shown that arsenic exposure augments the risk of bone disorders. However, the detailed effect and mechanism of inorganic arsenic on osteoblast differentiation of bone marrow stromal cells and bone loss still remain unclear.Objectives: We investigated the effects and mechanism of arsenic on osteoblast differentiation in vitro and evaluated bone mineral density (BMD) and bone microstructure in rats at doses relevant to human exposure from drinking water.Methods: We used a cell model of rat primary bone marrow stromal cells (BMSCs) and a rat model of long-term exposure with arsenic-contaminated drinking water, and determined bone microstructure and BMD in rats by microcomputed tomography (μCT).Results: We observed significant attenuation of osteoblast differentiation after exposure of BMSCs to arsenic trioxide (0.5 or 1 μM). After arsenic treatment during differentiation, expression of runt-related transcription factor-2 (Runx2), bone morphogenetic protein-2 (BMP-2), and osteocalcin in BMSCs was inhibited and phosphorylation of enhanced extracellular signal-regulated kinase (ERK) was increased. These altered differentiation-related molecules could be reversed by the ERK inhibitor PD98059. Exposure of rats to arsenic trioxide (0.05 or 0.5 ppm) in drinking water for 12 weeks altered BMD and microstructure, decreased Runx2 expression, and increased ERK phosphorylation in bones. In BMSCs isolated from arsenic-treated rats, osteoblast differentiation was inhibited.Conclusions: Our results suggest that arsenic is capable of inhibiting osteoblast differentiation of BMSCs via an ERK-dependent signaling pathway and thus increasing bone loss.Citation: Wu CT, Lu TY, Chan DC, Tsai KS, Yang RS, Liu SH. 2014. Effects of arsenic on osteoblast differentiation in vitro and on bone mineral density and microstructure in rats. Environ Health Perspect 122:559–565; http://dx.doi.org/10.1289/ehp.1307832

Water purification of arsenic-contaminated drinking water via air gap membrane distillation (AGMD)

Arsenic contamination in shallow tubewell water is a serious health issue in Bangladesh and other Southeast Asian countries. Rural and remote areas in these locations continue to face tremendous challenges in providing access to affordable and safe arsenic-free drinking water. In recent years, intensive efforts have been undertaken to identify appropriate technologies for arsenic removal. This study examines one approach by investigating the application of suitable membrane technologies, specifically air gap membrane distillation (AGMD), as a promising method for small-scale, low cost deployment. The objective of this study was to test an AGMD commercial prototype (nominal capacity of 2 L/hr) with three different feedstocks: arsenic-containing groundwater (medium concentration) and arsenic-spiked tap water (medium and high concentrations). Results show that the tested AGMD prototype is capable of achieving excellent separation efficiency, as all product water samples showed arsenic levels well below WHO accepted limits (10 µg/L) even for initial concentrations over 1800 µg/L. Parametric studies with focus on variation of coolant temperature illustrate the possibility of integrating AGMD in various thermal systems.

Relationship between drinking water and toenail arsenic concentrations among a cohort of Nova Scotians

Consumption of arsenic-contaminated drinking water is associated with increased cancer risk. The relationship between arsenic body burden, such as concentrations in human toenails, and arsenic in drinking water is not fully understood. We evaluated the relationship between arsenic concentrations in drinking water and toenail clippings among a cohort of Nova Scotians. A total of 960 men and women aged 35 to 69 years provided home drinking water and toenail clipping samples. Information on water source and treatment use and covariables was collected through questionnaires. Arsenic concentrations in drinking water and toenail clippings and anthropometric indices were measured. Private drilled water wells had higher arsenic concentrations compared with other dug wells and municipal drinking water sources (P<0.001). Among participants with drinking water arsenic levels ≥1 μg/l, there was a significant relationship between drinking water and toenail arsenic concentrations (r=0.46, P<0.0001). Given similar levels of arsenic exposure from drinking water, obese individuals had significantly lower concentrations of arsenic in toenails compared with those with a normal weight. Private drilled water wells were an important source of arsenic exposure in the study population. Body weight modifies the relationship between drinking water arsenic exposure and toenail arsenic concentrations.

Metabolomic Analysis of the Effects of Chronic Arsenic Exposure in a Mouse Model of Diet-Induced Fatty Liver Disease

Arsenic is a widely distributed environmental component that is associated with a variety of cancer and non-cancer adverse health effects. Additional lifestyle factors, such as diet, contribute to the manifestation of disease. Recently, arsenic was found to increase inflammation and liver injury in a dietary model of fatty liver disease. The purpose of the present study was to investigate potential mechanisms of this diet-environment interaction via a high-throughput metabolomics approach. GC×GC-TOF MS was used to identify metabolites that were significantly increased or decreased in the livers of mice fed a Western diet (a diet high in fat and cholesterol) and co-exposed to arsenic-contaminated drinking water. The results showed that there are distinct hepatic metabolomic profiles associated with eating a high fat diet, drinking arsenic-contaminated water, and the combination of the two. Among the metabolites that were decreased when arsenic exposure was combined with a high fat diet were short-chain and medium-chain fatty acid metabolites and the anti-inflammatory amino acid, glycine. These results are consistent with the observed increase in inflammation and cell death in the livers of these mice and point to potentially novel mechanisms by which these metabolic pathways could be altered by arsenic in the context of diet-induced fatty liver disease.

Whole-Genome Sequencing Analysis Identifies a Distinctive Mutational Spectrum in an Arsenic-Related Lung Tumor

Arsenic exposure is a significant cause of lung cancer in North America and worldwide. Arsenic-related tumors are structurally indistinguishable from those induced by other carcinogens. Because carcinogens, like tobacco, induce distinctive mutational signatures, we sought to characterize the mutational signature of an arsenic-related lung tumor from a never smoker with the use of whole-genome sequencing. Tumor and lung tissues were obtained from a never smoker with lung squamous cell carcinoma (LUSC), without familiar history of lung cancer and chronically exposed to high levels of arsenic-contaminated drinking water. The Illumina HiSeq-2000 platform was used to sequence each genome at approximately 30-fold haploid coverage. The mutational signature was compared with those observed in previously characterized lung tumors. The arsenic-related tumor exhibited alterations common in LUSC, such as the increased number of copies at 3q26 (SOX2 locus). However, the arsenic-related genome not only harbored a lower number of point mutations, but also had a remarkably high fraction of T>G/A>C mutations and low fraction of C>A/G>T transversions, which is uncharacteristic of LUSCs. Furthermore, at the gene level, we identified a rare G>C mutation in TP53, which is uncommon in lung tumors in general (<0.2%) but has been observed in other arsenic-related malignancies. We generated the first whole-genome sequence of an LUSC from a never-smoker patient chronically exposed to arsenic, and identified a distinct mutational spectrum associated with arsenic exposure, providing novel evidence supporting the hypothesis that arsenic-induced lung tumors arise through molecular mechanisms that differ from those of the common lung cancer.

Emerging Arsenic Threat in Canada

L. Rodriguez-Lado et al. 's geostatistical model (“Groundwater arsenic contamination throughout China,” Reports, 23 August, p. [866][1]) has revealed the hidden risk of arsenic exposure in drinking water, particularly in China. The accompanying Perspective by H. A. Michael (“An arsenic forecast for China,” p. [852][1]) highlighted the global burden of arsenic-contaminated drinking water and the potential utility of Rodriguez-Lado's model to identify populations exposed to arsenic before the development of symptoms. In Canada, arsenic is not currently a primary public health concern. However, we would like to point out the urgency of this emerging threat. More than a quarter of a million tons of arsenic generated over 50 years during the operation of the Giant Mine in Yellowknife (Northern Canada) reside underground and in piles aboveground. Because cleanup is deemed too great a health risk, the arsenic will be frozen in the ground, at a cost of nearly one billion Canadian dollars ([ 1 ][2]). In almost every province, arsenic-contaminated drinking water is a growing health concern in Canada. From Nova Scotia to British Columbia, arsenic levels frequently exceed those deemed safe by the World Health Organization (WHO) ([ 2 ][3]). Tools such as those described by Rodgriguez-Lado et al. will not only help identify areas to prioritize for immediate action in Canada and around the world, but also encourage public health agencies to monitor those already chronically exposed. 1. [↵][4]B. Weber, “Giant Mine's high cleanup bill shakes up policy on toxic sites,” The Globe and Mail (1 April 2013). 2. [↵][5]1. C. F. McGuigan, 2. C. L. A. Hamula, 3. S. Huang, 4. S. Gabos, 5. X. C. Le , Environ. Rev. 18, 291 (2010). [OpenUrl][6][CrossRef][7][Web of Science][8] [1]: pending:yes [2]: #ref-1 [3]: #ref-2 [4]: #xref-ref-1-1 View reference 1 in text [5]: #xref-ref-2-1 View reference 2 in text [6]: {openurl}?query=rft.jtitle%253DEnviron.%2BRev.%26rft.volume%253D18%26rft.spage%253D291%26rft_id%253Dinfo%253Adoi%252F10.1139%252FA10-012%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [7]: /lookup/external-ref?access_num=10.1139/A10-012&link_type=DOI [8]: /lookup/external-ref?access_num=000285680400015&link_type=ISI

Retardation of arsenic transport through a Pleistocene aquifer

Groundwater drawn daily from shallow alluvial sands by millions of wells over large areas of South and Southeast Asia exposes an estimated population of over 100 million to toxic levels of arsenic (1). Holocene aquifers are the source of widespread arsenic poisoning across the region (2, 3). In contrast, Pleistocene sands deposited in this region more than ~12,000 years ago mostly do not host groundwater with high levels of arsenic. Pleistocene aquifers are increasingly used as a safe source of drinking water (4) and it is therefore important to understand under what conditions low levels of arsenic can be maintained. Here we reconstruct the initial phase of contamination of a Pleistocene aquifer near Hanoi, Vietnam. We demonstrate that changes in groundwater flow conditions and the redox state of the aquifer sands induced by groundwater pumping caused the lateral intrusion of arsenic contamination over 120 m from Holocene aquifer into a previously uncontaminated Pleistocene aquifer. We also find that arsenic adsorbs onto the aquifer sands and that there is a 16–20 fold retardation in the extent of the contamination relative to the reconstructed lateral movement of groundwater over the same period. Our findings suggest that arsenic contamination of Pleistocene aquifers in South and Southeast Asia as a consequence of increasing levels of groundwater pumping have been delayed by the retardation of arsenic transport.

Effect of therapeutic arsenic exposure on pulmonary function

Arsenic-contaminated drinking water has been associated with respiratory diseases and lung function impairment. Oral arsenic trioxide (ATO) is a standard treatment for acute promyelocytic leukaemia. This study aimed to explore the effect of therapeutic exposure to arsenic on lung function. This was a case-control cross-sectional study on patients with haematological malignancies with or without exposure to ATO. Full lung function tests and serum Clara cell protein 16 (CC16) were measured. There were 57 cases (arsenic exposed) and 57 matched controls (arsenic non-exposed) recruited. Among cases, the median duration of ATO exposure was 519 (194-1259) days. The mean FEV(1)/FVC ratio, FEV(1) (% predicted), and RV/TLC (%), as well as % subjects with FEV(1)/FVC below lower limits of normal (LLN), were similar in the two groups with or without arsenic exposure. However the mean TLC (% predicted) and DLCO/VA were significantly higher in arsenic-exposed versus non-exposed group (p = 0.01 and p = 0.008 respectively). There were mildly reduced FEV(1)/FVC ratio and FEF(25-75) (% predicted), largely within normal limits, among high level arsenic exposure compared with non-exposure (p = 0.01 and p = 0.05 respectively). Serum CC16 was comparable among both arsenic exposed and non-exposed groups. Therapeutic use of oral ATO for a median of around 1.5 years was not associated with clinically significant lung function impairment.

Upstream Water Piracy Contaminates Downstream Water

Abstract Arsenic contamination has affected the groundwater of the Ganges, Indus, and Mekong basins, afflicting millions of people with arsenicosis. In the Ganges basin, 20% of deaths are related to arsenic-contaminated drinking water. Site visitations to and surveys of surface water resources at the affected sites have identified land use and land cover changes as anthropogenic factors that have contributed to this disaster in the river basins. It was also found that due to the construction of dams and barrages upstream of the affected sites, the downstream water supply has been affected by water piracy and has consequently been reduced drastically to about 60%, with surface water resources, such as distributaries, flood plains, ponds, etc., becoming dry. The source of the arsenic contamination is attributed to alluvium-mixed arsenopyrites that are inactive under water but, as the groundwater table sinks following the continued absence of recharging water, form water-soluble compounds of arsenic after co...

Catalase has a key role in protecting cells from the genotoxic effects of monomethylarsonous acid: A highly active metabolite of arsenic

Although it is widely known that arsenic-contaminated drinking water causes many diseases, arsenic's exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as an important key event in the toxic MOA of arsenic. The authors' studies are centered on identifying a reactive species involved in the genotoxicity of arsenic using a catalase (CAT) knockout mouse model that is impaired in its ability to breakdown hydrogen peroxide (H2 O2 ). The authors assessed the induction of DNA damage using the Comet assay following exposure of mouse Cat(+/) (+) and Cat(-) (/) (-) primary splenic lymphocytes to monomethylarsonous acid (MMA(III) ) to identify the potential role of H2 O2 in mediating cellular effects of this metalloid. The results showed that the Cat(-) (/) (-) lymphocytes are more susceptible to MMA(III) than the Cat(+/) (+) lymphocytes by a small (1.5-fold) but statistically significant difference. CAT activity assays demonstrated that liver tissue has approximately three times more CAT activity than lymphocytes. Therefore, Comet assays were performed on primary Cat(+/) (+) , Cat(+/) (-) , and Cat(-) (/) (-) hepatocytes to determine if the Cat(-) (/) (-) cells were more susceptible to MMA(III) than lymphocytes. The results showed that the Cat(-) (/) (-) hepatocytes exhibit higher levels of DNA strand breakage than the Cat(+/) (+) (approximately fivefold) and Cat(+/) (-) (approximately twofold) hepatocytes exposed to MMA(III) . Electron spin resonance using 5,5-dimethyl-1-pyrroline-N-oxide as the spin-trap agent detected the generation of ·OH via MMA(III) when H2 O2 was present. These experiments suggest that CAT is involved in protecting cells against the genotoxic effects of the ·OH generated by MMA(III) .

Effect of Arsenic Contaminated Drinking Water on Human Chromosome: A Case Study

Arsenic contamination of ground water has become a serious problem all over the world. Large number of people from Uttar Pradesh, Bihar and West Bengal of India are suffering due to consumption of arsenic contaminated drinking water. Study was carried out on 30 individuals residing in Ballia District, UP where the maximum concentration of arsenic was observed around 0.37ppm in drinking water. Blood samples were collected from them to find out the problem related with arsenic. Cytogenetic study of the blood samples indicates that out of 30, two persons developed Klinefelter syndrome.

Expression of WWOX and FHIT is downregulated by exposure to arsenite in human uroepithelial cells

Ecological studies in Taiwan, Chile, Argentina, Bangladesh, and Mexico have confirmed significant dose-dependent associations between ingestion of arsenic-contaminated drinking water and the risk of various human malignancies. The FHIT and WWOX genes are active in common fragile sites FRA3B and FRA16D, respectively. Reduced expression of FHIT or WWOX is known to be an early indicator of carcinogen-induced cancers. However, the effect of arsenite on the expressions and molecular mechanisms of these markers is still unclear. The aims of this study were (i) to observe the expression of ATR, WWOX and FHIT proteins in urothelial carcinoma (UC) between endemic and non-endemic areas of blackfoot disease (BFD) by immunohistochemical analyses; (ii) to compare expression of these genes between arsenite-treated SV-HUC-1 human epithelial cells and rat uroepithelial cells; and (iii) to determine the role of DNMT and MEK inhibitors on expressions of WWOX and FHIT in response to arsenite in SV-HUC-1. The experiments revealed that expressions of ATR, WWOX and FHIT in UC significantly differed between BFD areas and non-BFD areas (p=0.003, 0.009 and 0.021, respectively). In fact, the results for the arsenite-treated groups showed that ATR, WWOX and FHIT are downregulated by arsenite in SV-HUC-1. However, the inhibitors suppressed the effects of arsenite on WWOX and FHIT proteins and mRNA expression. In conclusion, arsenite decreased expressions of ATR, WWOX and FHIT via ERK1/2 activation in SV-HUC-1 cells. These findings confirm that dysregulations of these markers may contribute to arsenite-induced carcinogenesis.