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PubMed2003

Arsenic groundwater contamination and sufferings of people in North 24-Parganas, one of the nine arsenic affected districts of West Bengal, India.

To understand the magnitude of the arsenic calamity in West Bengal, a detailed study spanning 7 years was made in North 24-Parganas, one of the nine arsenic affected districts. Area and population of North 24-Parganas district are 4093.82 sq. km and 7.3 million, respectively. Fourty eight thousand and thirty water samples were analyzed from hand tubewells of North 24-Parganas in use for drinking, cooking and 29.2% of the tubewells were found to have arsenic above 50 microg/L, the maximum permissible limit of World Health Organization (WHO) and 52.8% have arsenic above 10 microg/L, WHO recommended value of arsenic in drinking water. Out of the 22 blocks of North 24-Parganas, in 20 blocks arsenic has been found above the maximum permissible limit and so far in 16 blocks people have been identified as suffering from arsenical skin lesions. From the generated data, it is estimated that about 2.0 million and 1.0 million people are drinking arsenic contaminated water above 10 microg/L and 50 microg/L level, respectively in North 24-Parganas alone. So far, in our preliminary study 33,000 people have been examined at random from arsenic affected villages in North 24-Parganas and 2274 people have been registered with arsenical skin lesions. Extrapolation of the available data indicates about 0.1 million people may be suffering from arsenical skin lesions from North 24-Parganas alone. A sum of 21,000 hair, nail, and urine samples analyses from arsenic affected villages show 56%, 80%, and 87% people have arsenic in biological specimen more than normal/toxic (hair) level, respectively. Thus, many may be subclinically affected. Due to use of arsenic contaminated groundwater for agricultural irrigation, rice and vegetable are getting arsenic contaminated. Hence there is an additional arsenic burden from food chain. People from arsenic affected villages are also suffering from arsenical neuropathy. A followup study indicates that many of the victims suffering from severe arsenical skin lesions for several years are now suffering from cancer or have already died of cancer.

Adult↗
PubMed2004

Arsenic speciation in urine from acute promyelocytic leukemia patients undergoing arsenic trioxide treatment.

Arsenic has been used successfully in clinical trials for treating acute promyelocytic leukemia (APL). Although sublethal doses of inorganic arsenic are used, little is known about the pharmacokinetics and metabolism of the high levels of arsenic in APL patients. To fill this important gap, this study describes the speciation of arsenic in urine from four APL patients treated with arsenic. Each patient was injected daily with an arsenite (As(III)) solution that contained 10 mg of As(2)O(3) precursor. Speciation analysis of the patient urine samples collected consecutively for 48 h, encompassing two intravenous injections of arsenic, revealed the presence of monomethylarsonous acid (MMA(III)), dimethylarsinous acid (DMA(III)), monomethylarsonic acid (MMA(V)), and dimethylarsinic acid (DMA(V)). The intermediate methyl arsenic metabolites, MMA(III) and DMA(III), were detected in most urine samples from all of the patients when a preservative, diethyldithiocarbomate, was added to the urine samples to stabilize these trivalent arsenic species. The major arsenic species detected in the urine samples from the patients were As(III), MMA(V), and DMA(V), accounting for >95% of the total arsenic excreted. The relative proportions of As(III), As(V), MMA(V), and DMA(V) in urine samples collected 24 h after the injections of As(III) were 27.6 +/- 6.1, 2.8 +/- 2.0, 22.8 +/- 8.1, and 43.7 +/- 13.3%, respectively. The relatively lower fraction of the methylated arsenic species in these APL patients under arsenic treatment as compared with that from the general population exposed to much lower levels of arsenic suggests that the high levels of As(III) inhibit the methylation of arsenic (inhibits the formation of methyl arsenic metabolites). The arsenic species excreted into the urine accounted for 32-65% of the total arsenic injected. These results suggest that other pathways of excretion, such as through the bile, may play an important role in eliminating (removing) arsenic from the human body when challenged by high levels of As(III).

Adult↗
PubMed2003

Arsenic contamination of Bangladesh paddy field soils: implications for rice contribution to arsenic consumption.

Arsenic contaminated groundwater is used extensively in Bangladesh to irrigate the staple food of the region, paddy rice (Oryza sativa L.). To determine if this irrigation has led to a buildup of arsenic levels in paddy fields, and the consequences for arsenic exposure through rice ingestion, a survey of arsenic levels in paddy soils and rice grain was undertaken. Survey of paddy soils throughout Bangladesh showed that arsenic levels were elevated in zones where arsenic in groundwater used for irrigation was high, and where these tube-wells have been in operation for the longest period of time. Regression of soil arsenic levels with tube-well age was significant. Arsenic levels reached 46 microg g(-1) dry weight in the most affected zone, compared to levels below l0 microg g(-1) in areas with low levels of arsenic in the groundwater. Arsenic levels in rice grain from an area of Bangladesh with low levels of arsenic in groundwaters and in paddy soils showed that levels were typical of other regions of the world. Modeling determined, even these typical grain arsenic levels contributed considerably to arsenic ingestion when drinking water contained the elevated quantity of 0.1 mg L(-1). Arsenic levels in rice can be further elevated in rice growing on arsenic contaminated soils, potentially greatly increasing arsenic exposure of the Bangladesh population. Rice grain grown in the regions where arsenic is building up in the soil had high arsenic concentrations, with three rice grain samples having levels above 1.7 microg g(-1).

Agriculture↗
PubMed1998

Urinary excretion of arsenic species after exposure to arsenic present in drinking water.

The water from some drilled wells in southwest Finland contains high arsenic concentrations (min-max: 17-980 microg/L). We analyzed inorganic arsenic (As-i) and organic arsenic (monomethylarsonate [MMA] and dimethylarsinate [DMA]) species in urine and conducted a clinical examination of current users (n = 35) and ex-users (n = 12) of such wells. Ex-users had ceased to use the water from the wells 2-4 months previously. Urinary arsenic species were also analyzed from persons whose drinking water contained less than 1 microg/L of arsenic (controls, n = 9). The geometric means of the concentrations of total arsenic in urine were 58 microg/L for current users, 17 microg/L for ex-users, and 5 microg/L for controls. The excreted arsenic was associated with the calculated arsenic doses, and on average 63% of the ingested arsenic dose was excreted in urine. The ratios of MMA/DMA and As-i/As-tot (As-tot = As-i + MMA + DMA) in urine tended to be lower among the current users and in the higher exposure levels than in controls, suggesting that As-i was better methylated in current users. However, the differences were mainly explained by age; older persons were better methylators of inorganic arsenic than younger individuals. The arsenic content of hair correlated well with the past and chronic arsenic exposure; an increase of 10 microg/L in the arsenic concentration of the drinking water or an increase of 10-20 microg/day of the arsenic exposure corresponded to a 0.1 mg/kg increase in hair arsenic. The individuals were interviewed and complained of muscle cramps, mainly in the legs, and this was associated with elevated arsenic exposure. The present study demonstrates that arsenic methylation has no threshold at these exposure levels.

Adolescent↗
PubMed2004

Exposure to inorganic arsenic in soil increases urinary inorganic arsenic concentrations of residents living in old mining areas.

The short term human exposure studies conducted on populations exposed to high concentrations of inorganic arsenic in soil have been inconsistent in demonstrating a relationship between environmental concentrations and exposure measures. In Australia there are many areas with very high arsenic concentrations in residential soil most typically associated with gold mining activities in rural areas. This study aimed to investigate the relationship between environmental arsenic and urinary inorganic arsenic concentrations in a population living in a gold mining area (soil arsenic concentrations between 9 and 9900 mg kg(-1)), and a control population with low arsenic levels in soil (between 1 and 80 mg kg(-1)). Risk factors for increased urinary arsenic concentrations were also explored. There was a weak but significant relationship between soil arsenic concentrations and inorganic urinary arsenic concentration with a Spearman correlation coefficient of 0.39. When participants with greater than 100 mg kg(-1) arsenic in residential soil were selected, the coefficient increased to 0.64. The geometric mean urinary inorganic arsenic concentration for the exposed group was 1.64 microg L(-1) (<detection limit -28.4 microg L(-1)) and for the control group was 1.18 microg L(-1) (<detection limit -4.69 microg L(-1)). Participants with residential soil in excess of 1000 mg kg(-1) recorded a geometric mean urinary inorganic arsenic concentration of 2.46 microg L(-1). In a random effects linear regression model, soil arsenic concentration was the significant predictor of increased urinary arsenic concentrations. Season was shown to have a significant influence on urinary inorganic arsenic concentrations. Other factors such as age, gender and hours of contact with soil may also be important risk factors. These results show that high concentrations of arsenic in soil can make a contribution to urinary inorganic arsenic concentrations.

Adult↗
PubMed2003

Hair and toenail arsenic concentrations of residents living in areas with high environmental arsenic concentrations.

Surface soil and groundwater in Australia have been found to contain high concentrations of arsenic. The relative importance of long-term human exposure to these sources has not been established. Several studies have investigated long-term exposure to environmental arsenic concentrations using hair and toenails as the measure of exposure. Few have compared the difference in these measures of environmental sources of exposure. In this study we aimed to investigate risk factors for elevated hair and toenail arsenic concentrations in populations exposed to a range of environmental arsenic concentrations in both drinking water and soil as well as in a control population with low arsenic concentrations in both drinking water and soil. In this study, we recruited 153 participants from areas with elevated arsenic concentrations in drinking water and residential soil, as well as a control population with no anticipated arsenic exposures. The median drinking water arsenic concentrations in the exposed population were 43.8 micro g/L (range, 16.0-73 micro g/L) and median soil arsenic concentrations were 92.0 mg/kg (range, 9.1-9,900 mg/kg). In the control group, the median drinking water arsenic concentration was below the limit of detection, and the median soil arsenic concentration was 3.3 mg/kg. Participants were categorized based on household drinking water and residential soil arsenic concentrations. The geometric mean hair arsenic concentrations were 5.52 mg/kg for the drinking water exposure group and 3.31 mg/kg for the soil exposure group. The geometric mean toenail arsenic concentrations were 21.7 mg/kg for the drinking water exposure group and 32.1 mg/kg for the high-soil exposure group. Toenail arsenic concentrations were more strongly correlated with both drinking water and soil arsenic concentrations; however, there is a strong likelihood of significant external contamination. Measures of residential exposure were better predictors of hair and toenail arsenic concentrations than were local environmental concentrations.

Adult↗
PubMed2003

Pattern of excretion of arsenic compounds [arsenite, arsenate, MMA(V), DMA(V)] in urine of children compared to adults from an arsenic exposed area in Bangladesh.

Urinary arsenic is generally considered as the most reliable indicator of recent exposure to inorganic arsenic and is used as the main bio-marker of exposure. However, due to the different toxicity of arsenic compounds, speciation of arsenic in urine is generally considered to be more convenient for health risk assessment than measuring total arsenic concentration. Additionally, it can give valuable information about the metabolism of arsenic species within the body. In our study, for exposed group--42 urine samples were collected from Datterhat (South) village of Madaripur district, Bangladesh and an average arsenic concentration in their drinking water was 376 microg/L (range 118 to 620 microg/L). For control group, 27 urine samples were collected from a non-affected district, Badhadamil village of Medinipur district, West Bengal, India, where arsenic concentration in their drinking water is below 3 microg/L. The arsenic species in the urine were separated and quantified by using HPLC-ICP-MS. The sum of inorganic arsenic and its metabolites was also determined by FI-HG-AAS. Results indicate that average total urinary arsenic metabolites in children's urine is higher than adults and total arsenic excretion per kg body weight is also higher for children than adults. For arsenic species between adults and children, it has been observed that inorganic arsenic (In-As) in average is 2.36% and MMA is 6.55% lower for children than adults while DMA is 8.91% (average) higher in children than adults. The efficiency of the methylation process is also assessed by the ratio between urinary concentration of putative product and putative substrate of the arsenic metabolic pathway. Higher values mean higher methylation capacity. Results show the values of the MMA/In-As ratio for adults and children are 0.93 and 0.74 respectively. These results indicate that first reaction of the metabolic pathway is more active in adults than children. But a significant increase in the values of the DMA/MMA ratio in children than adults of exposed group (8.15 vs. 4.11 respectively) indicates 2nd methylation step is more active in children than adults. It has also been shown that the distribution of the values of DMA/MMA ratio to exposed group decrease with increasing age (2nd methylation process). Thus from these results we may infer that children retain less arsenic in their body than adults. This may also explain why children do not show skin lesions compared to adults when both are drinking same contaminated water.

Adult↗
PubMed2002

Arsenic speciation and distribution in an arsenic hyperaccumulating plant.

Arsenic-contaminated soil is one of the major arsenic sources for drinking water. Phytoremediation, an emerging, plant-based technology for the removal of toxic contaminants from soil and water, has been receiving renewed attention. Although a number of plants have been identified as hyperaccumulators for the phytoextraction of a variety of metals, and some have been used in field applications, no hyperaccumulator for arsenic had been previously reported until the recent discovery of Brake fern (Pteris vittata), which can hyperaccumulate arsenic from soils. This finding may open a door for phytoremediation of arsenic-contaminated soils. Speciation and distribution of arsenic in the plant can provide important information helpful to understanding the mechanisms for arsenic accumulation, translocation, and transformation. In this study, plant samples after 20 weeks of growth in an arsenic-contaminated soil were used for arsenic speciation and distribution study. A mixture of methanol/water (1:1) was used to extract arsenic compounds from the plant tissue. Recoveries of 85 to 100% were obtained for most parts of the plant (rhizomes, fiddle heads, young fronds and old fronds) except for roots, for which extraction efficiency was approximately 60%. The results of this study demonstrate the ability of Brake fern as an arsenic hyperaccumulator. It transfers arsenic rapidly from soil to aboveground biomass with only minimal arsenic concentration in the roots. The arsenic is found to be predominantly as inorganic species; and it was hypothesized that the plant uptakes arsenic as arsenate [As(V)I and arsenate was converted to arsenite [As(III)] within the plant. The mechanisms of arsenic uptake, translocation, and transformation by this plant are not known and are the objectives of our on-going research.

Arsenic↗
PubMedDate not supplied

Effects of arsenic concentrations and forms on arsenic uptake by the hyperaccumulator ladder brake.

Ladder brake (Pteris vittata L.) is a newly discovered arsenic hyperaccumulator. No information is available about arsenic effects on ladder brake. This study determined the effects of different arsenic concentrations (50 to 1000 mg kg(-1)) or forms (organic vs. inorganic and arsenite vs. arsenate) applied to soils on growth and arsenic uptake by ladder brake. Young plants were grown in a greenhouse for 12 or 18 wk. Ladder brake was highly tolerant of arsenic and survived in soil containing up to 500 mg As kg(-1). The fact that addition of arsenate up to 100 mg As kg(-1) increased fern biomass by 64 to 107%, coupled with higher arsenic concentration in younger fronds at low soil arsenic concentrations and older fronds at high soil arsenic concentrations, implies that arsenic may be beneficial for fern growth. Addition of 50 mg As kg(-1) was best for fern growth and arsenic accumulation, resulting in the highest fern biomass (3.9 g plant(-1)), bioconcentration factor (up to 63), and translocation factor (up to 25). With an exception of FeAsO4 and AlAsO4, which had the lowest effects due to their low solubility, little difference was observed among other arsenic forms mainly because of arsenic conversion in soil. Aboveground biomass was mostly responsible for accumulation of arsenic by plant (75-99%). Up to 26% of the added arsenic was removed by ladder brake, showing the high efficiency of ladder brake in arsenic removal. The results suggest that ladder brake may be a good candidate to remediate arsenic-contaminated soils.

Arsenic↗
PubMed2006

Arsenic in drinking water and peripheral nerve conduction velocity among residents of a chronically arsenic-affected area in Inner Mongolia.

BACKGROUND: It remains unclear whether chronic ingestion of arsenic in drinking water affects the peripheral nervous system. We examined the effects of arsenic exposure on nerve conduction velocity using electromyography. METHODS: A cross-sectional study was conducted of a population living in an arsenic-affected village in Hetao Plain, Inner Mongolia, China. A total of 134 (93.7%) of 143 inhabitants took part in the study, and 36 (76.6%) of 47 inhabitants in a low-arsenic exposed village were recruited as a control group. Of the participants, 109 inhabitants in the arsenic-affected village and 32 in the low-arsenic exposed village aged > or =18 years were used for the analyses. An expert physician performed skin examinations, and median nerve conduction velocity was examined by electromyography. Arsenic levels in tube-well water and urine were measured. A mean level of arsenic in tube-well water in the arsenic-affected village was 158.3 microg/L, while that in the low-arsenic exposed village was 5.3 microg/L. RESULTS: No significant differences in the means of the motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) were observed in relation to arsenic levels in tube wells, urine, and the duration of tube-well use. Further, no differences in mean MCV or SCV were found between the subjects with and without arsenic dermatosis, with mean SCV of 52.8 m/s (SD 6.3) in those without and 54.6 m/s (5.2) in subjects with arsenic dermatosis (p=0.206). CONCLUSION: These findings suggest that chronic arsenic poisoning from drinking water is unlikely to affect nerve conduction velocity, at least within the range of arsenic in drinking water examined in the present study.

Adolescent↗
PubMed2005

Can homeopathic arsenic remedy combat arsenic poisoning in humans exposed to groundwater arsenic contamination?: a preliminary report on first human trial.

Groundwater arsenic (As) has affected millions of people globally distributed over 20 countries. In parts of West Bengal (India) and Bangladesh alone, over 100 million people are at risk, but supply of As-free water is grossly inadequate. Attempts to remove As by using orthodox medicines have mostly been unsuccessful. A potentized homeopathic remedy, Arsenicum Album-30, was administered to a group of As affected people and thereafter the As contents in their urine and blood were periodically determined. The activities of various toxicity marker enzymes and compounds in the blood, namely aspartate amino transferase, alanine amino transferase, acid phosphatase, alkaline phosphatase, lipid peroxidation and reduced glutathione, were also periodically monitored up to 3 months. The results are highly encouraging and suggest that the drug can alleviate As poisoning in humans.

Journal Article↗
PubMed1976

[Arsenic metabolism. (17) Studies of placental transfer of arsenic and the effects of antidotes and diet].

Albino rats of Wistar strain (Tamura 1950) breeded in a closed colony were administered arsenic trioxide orally during pregnancy (from the 0 day to the 20th day). Organs of fetuses and mother rats were exenterated on the 21st day of gestation and the contents of arsenic measured using an arsenic analyzer unit with atomic absorption spectrophotometry. Whole organs of the fetus were separated into 3 groupings i.e. liver, brain and remaining organs. The contents of arsenic in the organs in each of these groupings and in the placenta were measured. Even in the non-administered group, arsenic was detected in the every organ. In the arsenic administered group, the content of arsenic in the placenta was the highest among the four preparations tested; and the content in the liver and remaining organs was considerably high, but was low in the brain. The level of accumulation of arsenic differed between each organ. In the placenta, the accumulation reached a plateau, and in the brain this accumulation was below one-tenth that in the liver. In the non-administered group, arsenic was detected in the liver, kidney, spleen and brain of mother rats. In the group on arsenite, the content in the kidney and spleen was large, followed by a large amount in the liver and in the brain respectively. The level of accumulation of arsenic in mother rats differed between each organ. Arsenite was administered with antidotes such as dimercaprol, thioctic acid and L-ascorbic acid during pregnancy (from the 0 day to the 5th day). In this group the content of arsenic in the remaining organs was statistically less than that of the control group. The content in the brain was slightly reduced by a co-administration of the antidotes, however, there was no statistical difference in the placenta and liver between the antidote-treated and control groups. The content of arsenic in the kidney of mother rats treated with antidotes was statistically less than that of the controls. Whether or not the content of arsenic in organs of fetuses and mother rats was affected by a milk diet was also studied. The content of arsenic in the organs of fetuses showed no statistical difference between the animals on an Oriental stock diet group and those on the milk diet. On the other hand, the content of arsenic in the kidney of mother rats on the milk diet was statistically less than seen in those in the Oriental stock diet group.

Animals↗
PubMed2006

Arsenic exposure alters hepatic arsenic species composition and stress-mediated gene expression in the common killifish (Fundulus heteroclitus).

In the present paper, we examine how arsenic species accumulate in fish liver and explore the hypothesis that sublethal arsenic concentrations in fish hepatic tissue interfere with stress-mediated gene expression. We exposed killifish (Fundulus heteroclitus) to 787 or 0 microg/L arsenic in tank water for 2 weeks. Arsenic exposure elevated total liver arsenic from 3.4 microg/g wet weight (control fish) to 9.6 microg/g wet weight, and resulted in a higher relative proportion of toxic (e.g. monomethylarsenous acid, dimethylarsenous acid, arsenic V) versus benign (arsenobetaine) arsenic species in this tissue. Following the exposure period, arsenic-treated and control fish were then subjected to a stress protocol: confinement and mechanical chasing for 15 min every 3 h. Liver tissue and blood were sampled from fish not exposed to the stressor at time 0, and at 8, 12, 24 and 40 h following the first stressor. Concentrations of the stress hormone cortisol increased significantly, and glucocorticoid receptor mRNA levels increased and then decreased in both groups, but patterns were nearly identical between arsenic pre-treated and arsenic untreated fish. Prior arsenic exposure prevented the stress-induced increases in stress-responsive LDH-B mRNA levels and enzyme activity observed in fish that had not been exposed to arsenic. However, in another stress-responsive gene, PEPCK, arsenic did not interfere with the stress-induced increase in gene expression, suggesting that the effects of arsenic on stress-mediated gene expression are complex and may involve regulatory pathways that differ between these two genes.

Animals↗
PubMed2002

Stability of arsenic species and insoluble arsenic in human urine.

Urinary arsenic species are important short-term biomarkers that have been used in epidemiological studies. However, the stability of soluble arsenic species and the amount of arsenic lost during sample pretreatment remain unclear. The objective of this study is to evaluate the stability of soluble arsenic species in urine and aqueous standards, as well as to assess the amount of insoluble and soluble arsenic lost during pretreatment (centrifugation and filtration, respectively). High-performance liquid chromatogram inductively coupled plasma mass spectrometry was used to speciate arsenic species [Arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid [MMA(V)], monomethylarsonous acid [MMA(III)], dimethylarsinic acid [DMA(V)], and arsenobetaine [AsB]] in aqueous standards and in urine samples. The arsenic levels in both freshly collected urine samples (pH = 5.5-7.0) and National Institute of Standards and Technology Standard Reference Material 2670 toxic elements in frozen-dried urine (pH 4.4) remained constant up to 6 months when stored at -20 degrees C. In an aqueous solution mixed with 10 micro g/liter of As(III), As(V), MMA, and DMA standards, and stored at 4 degrees C, As(III) and As(V) were stable only up to 4 weeks, and MMA and DMA remained stable up to 4.5 months. The same phenomenon was observed for 100 micro g/liter mixed aqueous standards. There was no significant loss of arsenic species in urine (<5%) when passed through a 0.45- micro m filter. The amounts of insoluble arsenic in urine lost during centrifuge ranged from 1/2 to 1/17 of soluble arsenic. These findings indicated that the urinary matrix plays an important role in stabilizing arsenic species. Also, the loss of insoluble arsenic in urine during centrifuging results in underestimation of arsenic exposure, and may explain the lack of an association between arsenic exposure and the risk of health outcomes reported in some epidemiological studies.

Arsenates↗
PubMed2002

Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China.

Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such overexposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.

Adult↗
PubMed2002

Chronic arsenic-exposed human prostate epithelial cells exhibit stable arsenic tolerance: mechanistic implications of altered cellular glutathione and glutathione S-transferase.

Acquisition of stable arsenic tolerance in human cells following chronic arsenic exposure has not been previously reported. In the present work, we describe acquisition of stable arsenic tolerance in the human prostate epithelial cell line RWPE-1 following chronic arsenic exposure in vitro. RWPE-1 cells continuously exposed to 5 microM sodium arsenite for > or =18 weeks exhibited dramatic resistance to acute arsenite toxicity. The LC50 for acute arsenite exposure in these chronic arsenic-exposed prostate epithelial (CAsE-PE) cells was 43.8 microM versus 17.6 microM in control cells. Similar results were obtained using the antineoplastic agent arsenic trioxide. This tolerance was stable, as CAsE-PE cells grown in arsenic-free medium for 5 weeks retained their resistant phenotype. Compared to control cells, CAsE-PE cells showed a 90% reduction in arsenic accumulation over 24 h coupled with a 2.6-fold increase in the rate of arsenic efflux. CAsE-PE cells had increased basal GSH levels (4.9-fold) and increased GST activity (2.4-fold) and both GSH depletion and inhibition of GST activity abolished arsenic tolerance. Arsenic tolerance was also abolished by treatment with inhibitors of the Mdr1 and Mrp1 transporters, although no increases in mdr1 or mrp1 gene expression were observed. Our results indicate that this tolerance in human cells involves increases in GSH levels and GST activity that allow for more efficient arsenic efflux by MRP1 and MDR1. This study represents the first report of stable acquired arsenic tolerance in human cells, which could have important implications for both the toxicology and the pharmacology of arsenic.

Adaptation, Physiological↗
PubMed2005

Chronic arsenic exposure and urinary 8-hydroxy-2'-deoxyguanosine in an arsenic-affected area in Inner Mongolia, China.

OBJECTIVE: Recent studies have shown that generation of reactive oxidants during arsenic metabolism can play an important role in arsenic-induced injury. The purpose of this study was to examine the relationship between arsenic in drinking water and oxidative stress in humans by measuring 8-Hydroxy-2'-deoxyguanosine (8-OHdG). METHODS: We performed a cross-sectional study in an arsenic-affected village in Hetao Plain, Inner Mongolia, China. A total of 134 of the 143 inhabitants (93.7%) of the village participated in the study. The levels of 8-OHdG, arsenic and its metabolites were measured in urine collected from the participants. Regression analyses were performed to investigate the relationship between arsenic species and 8-OHdG levels in urine. RESULTS: In the polluted village, monomethylarsenic was significantly higher in subjects with arsenic dermatosis than those without dermatosis despite no difference in mean levels of arsenic in well water between both types of subject. For subjects with arsenic dermatosis, arsenic species and metabolites in urine are significantly associated with 8-OHdG, while there was no statistically significant relationship for subjects without arsenic dermatosis. For all residents of the polluted village, the levels of dimethylarsenic and 8-OHdG were significantly higher for those who had been exposed to well water for more than 12 years. CONCLUSIONS: These results provide evidence of a link between exposure to arsenic from drinking water and oxidative stress, which may play an important role in arsenic-involved injuries.

8-Hydroxy-2'-Deoxyguanosine↗