Distribution of urinary selenium and arsenic among pregnant women exposed to arsenic in drinking water

Inorganic arsenic (In-As) is a well-known toxicant and carcinogen found naturally in surface and groundwater around the world. Exposure can cause skin lesions, adverse reproductive outcomes, and cancer. There are two main pathways of arsenic (As) metabolism in humans: the reduction reactions, and the oxidative methylation reactions, where methyl groups are attached to As compounds to form monomethylarsenate (MMA) and dimethylarsenate (DMA). MMA, DMA, and In-As are excreted in urine. Urinary levels of another metalloid, selenium (Se), have recently been shown to be associated with increased As excretion and altered metabolite distribution. This study investigates this association, using data collected in a larger prospective study of arsenic and reproductive effects in Chile. This analysis included 93 pregnant women from Antofagasta. Data on demographic, behavioral, and other characteristics were obtained via interviews conducted by trained midwives, and spot urine samples were analyzed for As and Se concentration using inductively coupled plasma-mass spectrometry (ICP-MS). Urinary Se levels were found to be correlated with urinary As levels in bivariate analysis (r = 0.68, P < 0.01). Multiple linear regression analyses revealed that higher urinary Se levels were associated with increased urinary As excretion, increased %DMA, and decreased %In-As. The results of this study suggest that in populations exposed to arsenic, Se intake may be correlated with urinary As excretion, and may alter As methylation.     

Arsenic methylation patterns before and after changing from high to lower concentrations of arsenic in drinking water.

Inorganic arsenic (In-As), an occupational and environmental human carcinogen, undergoes biomethylation to monomethylarsonate (MMA) and dimethylarsinate (DMA). It has been proposed that saturation of methylation capacity at high exposure levels may lead to a threshold for the carcinogenicity of In-As. The relative distribution of urinary In-As, MMA, and DMA is used as a measure of human methylation capacity. The most common pathway for elevated environmental exposure to In-As worldwide is through drinking water. We conducted a biomarker study in northern Chile of a population chronically exposed to water naturally contaminated with high arsenic content (600 micrograms/l). In this paper we present the results of a prospective follow-up of 73 exposed individuals, who were provided with water of lower arsenic content (45 micrograms/l) for 2 months. The proportions of In-As, MMA, and DMA in urine were compared before and after intervention, and the effect of other factors on the distribution of arsenic metabolites was also analyzed. The findings of this study indicate that the decrease in arsenic exposure was associated with a small decrease in the percent In-As in urine (from 17.8% to 14.6%) and in the MMA/DMA ratio (from 0.23 to 0.18). Other factors such as smoking, gender, age, years of residence, and ethnicity were associated mainly with changes in the MMA/DMA ratio, with smoking having the strongest effect. Nevertheless, the factors investigated accounted for only about 20% of the large interindividual variability observed. Genetic polymorphisms in As-methylating enzymes and other co-factors are likely to contribute to some of the unexplained variation. The changes observed in the percent In-As and in the MMA/DMA ratio do not support an exposure-based threshold for arsenic methylation in humans.     

Variability in human metabolism of arsenic

Estimating the nature and extent of human cancer risks due to arsenic (As) in drinking water is currently of great concern, since millions of persons worldwide are exposed to arsenic, primarily through natural enrichment of drinking water drawn from deep wells. Humans metabolize and eliminate As through oxidative methylation and subsequent urinary excretion. While there is debate as to the role of methylation in activation/detoxification, variations in arsenic metabolism may affect individual risks of toxicity and carcinogenesis. Using data from three populations, from Mexico, China, and Chile, we have analyzed the distribution in urine of total arsenic and arsenic species (inorganic arsenic (InAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA). Data were analyzed in terms of the concentration of each species and by evaluating MMA:DMA and (MMA+DMA):InAs ratios. In all persons most urinary As was present as DMA. Male:female differences were discernible in both high- and low-exposure groups from all three populations, but the gender differences varied by populations. The data also indicated bimodal distributions in the ratios of DMA to InAs and to MMA. While the gene or genes responsible for arsenic methylation are still unknown, the results of our studies among the ethnic groups in this study are consistent with the presence of functional genetic polymorphisms in arsenic methylation leading to measurable differences in toxicity. This analysis highlights the need for continuing research on the health effects of As in humans using molecular epidemiologic methods.     

Family correlations of arsenic methylation patterns in children and parents exposed to high concentrations of arsenic in drinking water

We investigated the evidence of a familial contribution to urinary methylation patterns in families ingesting arsenic in drinking water. Arsenic methylation can be assessed by measuring urinary levels of inorganic arsenic (InAs) and its methylated metabolites, monomethylarsonate (MMA), and dimethylarsinate (DMA). Methylation activity is reflected in the ratios: InAs/methylated arsenic (InAs/metAs) and MMA/DMA. Eleven families from Chile were selected because of their long-term exposure to very high levels of arsenic in drinking water (735-762 microg/L). Each family consisted of a father, a mother, and two children. We measured urinary arsenic and its methylated metabolites for each participant (n = 44). The intraclass correlation coefficients showed that 13-52% of the variations in the methylation patterns were from being a member of a specific family. Family correlations were calculated for father-mother, parent-child, and sibling-sibling pairs. Methylation patterns correlated strongly between siblings [r = 0.78 for InAs/metAs, 95% confidence interval (CI), 0.34-0.94; r = 0.82 for MMA/DMA, 95%CI, 0.43-0.95] compared to lower correlations in father-mother pairs (r = 0.18, r = -0.01, respectively), after adjustment for total urinary arsenic, age, and sex. Family correlations were not notably altered when adjustments were made for specific blood micronutrients (methionine, homocysteine, folate, vitamin B6, selenium, and vitamin B12 potentially related to methylation. We also report on a family pedigree with high prevalence of arsenic-induced effects. Participants from this family had low InAs/metAs values, which is consistent with increased toxicity of trivalent methylated arsenic species. Despite our small sample size, we observed that methylation patterns aggregate in families and are correlated in siblings, providing evidence of a genetic basis for the variation in arsenic methylation. Larger studies with more extensive pedigrees will need to be conducted to confirm these findings.     

饮水型砷暴露对人群甲基化代谢能力的影响

目的探讨饮水型砷暴露对人群甲基化代谢能力的影响。方法以带有砷化物预处理装置的原子吸收分光光度计测定砷暴露人群及无砷暴露对照人群血、尿中无机砷(iAs)、甲基胂(MMA)、二甲基胂(DMA)含量。以iAs、MMA及DMA的总和表示总胂(tAs)水平;以(MMA+DMA)/tAs及DMA/(MMA+DMA)分别计算一甲基化率(PMI)和二甲基化率(SMI)水平。结果砷暴露人群血中iAs、MMA、DMA、tAs及PMI水平均显著高于相应对照人群的水平,而SMI水平显著低于对照人群。尿中MMA水平分别与血中PMI及SMI水平呈显著正相关(r=0.419,P<0.01)及负相关(r=-0.326,P<0.05)。暴露组和对照组血中各种砷化物水平及甲基化率水平在男女间差异无显著性。结论砷暴露人群与无砷暴露人群相比甲基化率有差异,PMI显著增高,SMI显著降低。人群甲基化率无显著性别差异。     

Intra-individual variation in the metabolism of inorganic arsenic

OBJECTIVE: Inorganic arsenic is metabolized to methylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are excreted in the urine. Previous studies have shown a marked inter-individual variation in the metabolism, but the within-person variation is unknown. Therefore, we determined the variation in the relative amount of urinary arsenic metabolites, i.e., inorganic arsenic, MMA and DMA, over time in women living in an Andean village with elevated arsenic levels in drinking water. METHODS: For our investigation of the individual day-to-day variation, daily spot urine samples were collected (at the same time of the day) for 5 consecutive days by 15 women. For our investigation of the within-day variation, seven women collected all the urine voided over a 72-h period, each voided into a separate container. RESULTS: Repeated measures analysis of variance (ANOVA) revealed no significant day-to-day variation, either in the relative distribution of inorganic arsenic metabolites (inorganic arsenic, MMA and DMA), or in the concentration of the metabolites. However, the percentage of DMA was slightly higher (on average 5.0%; P=0.003) and the percentage of inorganic arsenic lower (on average 5.8%; P=0.001) during the morning/day (03:00-15:00) compared with the evening/night (15:00-03:00). No within-day variation in the percentage of MMA was observed. CONCLUSION: The arsenic methylation efficiency of an individual is remarkably stable over time.     

Methylation study of a population environmentally exposed to arsenic in drinking water.

Methylation is considered the detoxification pathway for inorganic arsenic (InAs), an established human carcinogen. Urinary speciation analysis is used to assess the distribution of metabolites [monomethylarsonate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], as indicators of methylation capacity. We conducted a large biomarker study in northern Chile of a population chronically exposed to high levels of arsenic in drinking water. We report the results of the methylation study, which focused on the effects of exposure and other variables on the percent InAs, MMA, DMA, and the ratio of MMA to DMA in urine. The study consisted of 122 people in a town with arsenic water levels around 600 micrograms/l and 98 participants in a neighboring town with arsenic levels in water of about 15 micrograms/l. The corresponding mean urinary arsenic levels were 580 micrograms/l and 60 micrograms/l, of which 18.4% and 14.9% were InAs, respectively. The main differences were found for MMA:DMA; exposure, smoking, and being male were associated with higher MMA:DMA, while longer residence, Atacameño ethnicity, and being female were associated with lower MMA:DMA. Together, these variables explained about 30% of the variability in MMA:DMA. Overall, there was no evidence of a threshold for methylation capacity, even at very high exposures, and the interindividual differences were within a much wider range than those attributed to the variables investigated. The differences in percent InAs were small and within the ranges of other studies of background exposure levels. The biological significance of MMA:DMA, which was more than 1.5 times greater in the exposed group, and its relationship to sex, length of exposure, and ethnicity need further investigation because its relevance to health risk is not clear.     

Consumption of folate-related nutrients and metabolism of arsenic in Bangladesh

BACKGROUND: Inorganic arsenic (InAs) is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and this methylation facilitates urinary arsenic excretion. Previous studies suggest that persons with more complete methylation, characterized as greater proportions of DMA and lesser proportions of MMA and InAs in urine, have a lower risk of adverse arsenic-related health outcomes. OBJECTIVE: The purpose of this study was to examine whether the capacity to methylate arsenic differs by nutrient intake. DESIGN: Participants were 1016 Bangladeshi adults exposed to arsenic in drinking water. Nutrient intake was assessed with a validated food-frequency questionnaire. Multivariate regression analyses were used to examine associations of nutrients with urinary arsenic metabolite profiles. RESULTS: In multivariate analyses, higher intakes of cysteine, methionine, calcium, protein, and vitamin B-12 were associated with lower percentages of InAs and higher ratios of MMA to InAs in urine. Higher intakes of niacin (beta=0.22, P=0.02) and choline (beta=0.10, P=0.02) were associated with higher DMA-to-MMA ratios, after adjustment for age, sex, smoking, total urinary arsenic, and total energy intake. CONCLUSIONS: Findings from the current study show the influence of multiple nutrients on arsenic methylation. In particular, this study highlights the potential importance of dietary intakes of cysteine, methionine, niacin, vitamin B-12, and choline on health effects of arsenic by modulating its metabolism.     

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

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.     

Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh

BACKGROUND: Populations in South and East Asia and many other regions of the world are chronically exposed to arsenic-contaminated drinking water. To various degrees, ingested inorganic arsenic (InAs) is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via folate-dependent one-carbon metabolism; impaired methylation is associated with adverse health outcomes. Consequently, folate nutritional status may influence arsenic methylation and toxicity. OBJECTIVE: The objective of this study was to test the hypothesis that folic acid supplementation of arsenic-exposed adults would increase arsenic methylation. DESIGN: Two hundred adults in a rural region of Bangladesh, previously found to have low plasma concentrations of folate (相似文献   

Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a Michigan population with low levels of arsenic in drinking water

The large disparity between arsenic concentrations in drinking water and urine remains unexplained. This study aims to evaluate predictors of urinary arsenic in a population exposed to low concentrations (≤50?μg/l) of arsenic in drinking water. Urine and drinking water samples were collected from a subsample (n=343) of a population enrolled in a bladder cancer case-control study in southeastern Michigan. Total arsenic in water and arsenic species in urine were determined using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was obtained through a self-reported food intake questionnaire. Log(10)-transformed drinking water arsenic concentration at home was a significant (P<0.0001) predictor of SumAs (R(2)=0.18). Associations improved (R(2)=0.29, P<0.0001) when individuals with less than 1?μg/l of arsenic in drinking water were removed and further improved when analyses were applied to individuals who consumed amounts of home drinking water above the median volume (R(2)=0.40, P<0.0001). A separate analysis indicated that AsB and DMA[V] were significantly correlated with fish and shellfish consumption, which may suggest that seafood intake influences DMA[V] excretion. The Spearman correlation between arsenic concentration in toenails and SumAs was 0.36 and between arsenic concentration in toenails and arsenic concentration in water was 0.42. Results show that arsenic exposure from drinking water consumption is an important determinant of urinary arsenic concentrations, even in a population exposed to relatively low levels of arsenic in drinking water, and suggest that seafood intake may influence urinary DMA[V] concentrations.     

Metabolism of inorganic arsenic in children with chronic high arsenic exposure in northern Argentina.

This study concerns the metabolism of inorganic arsenic (As) in children in three villages in northern Argentina: San Antonio de los Cobres and Taco Pozo, each with about 200 microg As/l in the drinking water, and Rosario de Lerma, with 0.65 microg As/l. Findings show that the concentrations of As in the blood and urine of the children in the two As-rich villages were on average 9 and 380 microg/l, respectively, the highest ever recorded for children. The concentrations were about 10 and 30 times higher for blood and urine, respectively, than in Rosario de Lerma. Total As in urine was only slightly higher than the sum of metabolites of inorganic As (U-Asmet), i.e., inorganic As, methylarsonic acid (MMA), and dimethylarsinic acid (DMA); this shows that inorganic As was the main form of As ingested. In contrast to previous studies on urinary metabolites of inorganic As in various population groups, the children and women in the present study excreted very little MMA. Thus, there seems to be a polymorphism for the enzymes (methyltransferases) involved in the methylation of As. Interestingly, the children had a significantly higher percentage of inorganic As in urine than the women, about 50% versus 32%. Also, the percentage of inorganic As in the children is considerably higher than in previous studies on children (about 13% in the two studies available) and adults (about 15-25%) in other population groups. This may indicate that children are more sensitive to As-induced toxicity than adults, as the methylated metabolites bind less to tissue constituents than inorganic As. In the children, the percentage inorganic arsenic in urine decreased, and the percentage of DMA increased with increasing U-Asmet, indicating an induction of As methylation with increasing exposure.     

Creatinine, diet, micronutrients, and arsenic methylation in West Bengal, India

Background: Ingested inorganic arsenic (InAs) is methylated to monomethylated (MMA) and dimethylated metabolites (DMA). Methylation may have an important role in arsenic toxicity, because the monomethylated trivalent metabolite [MMA(III)] is highly toxic.Objectives: We assessed the relationship of creatinine and nutrition—using dietary intake and blood concentrations of micronutrients—with arsenic metabolism, as reflected in the proportions of InAS, MMA, and DMA in urine, in the first study that incorporated both dietary and micronutrient data.Methods: We studied methylation patterns and nutritional factors in 405 persons who were selected from a cross-sectional survey of 7,638 people in an arsenic-exposed population in West Bengal, India. We assessed associations of urine creatinine and nutritional factors (19 dietary intake variables and 16 blood micronutrients) with arsenic metabolites in urine.Results: Urinary creatinine had the strongest relationship with overall arsenic methylation to DMA. Those with the highest urinary creatinine concentrations had 7.2% more arsenic as DMA compared with those with low creatinine (p < 0.001). Animal fat intake had the strongest relationship with MMA% (highest tertile animal fat intake had 2.3% more arsenic as MMA, p < 0.001). Low serum selenium and low folate were also associated with increased MMA%.Conclusions: Urine creatinine concentration was the strongest biological marker of arsenic methylation efficiency, and therefore should not be used to adjust for urine concentration in arsenic studies. The new finding that animal fat intake has a positive relationship with MMA% warrants further assessment in other studies. Increased MMA% was also associated, to a lesser extent, with low serum selenium and folate.     

Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite,monomethylarsonate, or dimethylarsinate in man

Summary The urinary elimination of the metabolites of arsenic has been followed up as a function of time in volunteers who ingested a single oral dose of arsenic (500 g As) either as sodium arsenite (As_i), monomethylarsonate (MMA), or cacodylate (DMA). The excretion rate increased in the order As_i < DMA < MMA. After 4 days, the amount of arsenic excreted in urine represents 46, 78, and 75% of the ingested dose in the case of As_i, MMA and DMA, respectively. With regard to the in vivo biotransformations, it is concluded that DMA is excreted unchanged; MMA is slightly (13%) methylated into DMA while roughly 75% of the arsenic excreted after ingestion of As_i is methylated arsenic (about 1/3 as MMA and about 2/3 as DMA).This study was supported by a grant from the Commission of the European Communities     

外源性蛋氨酸对饮水砷暴露雌性小鼠体内砷形态分布的影响

目的 探讨外源性蛋氨酸(methionine,Met)对饮水砷暴露小鼠体内不同组织器官砷形态分布的影响.方法 将健康清洁级雌性昆明小鼠40只,随机分为对照组、单纯砷染毒组及低、中、高剂量Met与砷联合染毒组,每组8只.除对照组小鼠饮蒸馏水外,其余各组小鼠以自由饮水方式饮含50mg/L亚砷酸钠的水,连续染毒4周.在染毒的第4周,低、中、高剂量Met与砷联合染毒组小鼠分别被腹腔注射100、200、400 mg/kg的Met溶液,对照组和单纯砷染毒组小鼠被腹腔注射生理盐水,连续注射7 d.末次注射24 h后,处死小鼠,快速取血,分离肝和脑组织,分别检测无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)含量,并计算各组织中总砷含鼍(TAs)及砷一甲基化率(primary methylation ratio,PMR)和二甲基化率(secondary methylation ratio,SMR).结果 单纯砷染毒组和高、中、低剂量Met与砷联合染毒组小鼠肝、脑组织及全血中iAs、MMA、DMA和TAs含量均高于对照组,差异有统计学意义(P<0.05).与单纯砷染毒组比较,中、高剂量Met与砷联合染毒组小鼠肝组织中DMA含量和PMR较高,差异有统计学意义(P<0.05).与单纯砷染毒组比较,各剂量Met与砷联合染毒组小鼠全血中iAs、MMA和TAs含量均下降,差异有统计学意义(P<0.05).各剂量Met与砷联合染毒组小鼠脑组织中DMA和TAs含量低于单纯砷染毒组,差异有统计学意义(P<0.05).结论 外源性Met 对小鼠体内砷甲基化代谢具有促进作用,并可加速体内砷化物的排泄,从而减少血液和脑组织中的砷负荷.     

Dietary intake and arsenic methylation in a U.S. population

Millions of people worldwide are exposed to arsenic-contaminated drinking water, and ingestion of inorganic arsenic (InAs) has been associated with increased risks of cancer. The primary metabolic pathway of ingested InAs is methylation to monomethyl arsenic (MMA) and dimethyl arsenic (DMA). However, people vary greatly in the degree to which they methylate InAs, and recent evidence suggests that those who excrete high proportions of ingested arsenic as MMA are more susceptible than others to arsenic-caused cancer. To date, little is known about the factors that determine interindividual differences in arsenic methylation. In this study, we assessed the effect of diet on arsenic metabolism by measuring dietary intakes and urinary arsenic methylation patterns in 87 subjects from two arsenic-exposed regions in the western United States. Subjects in the lower quartile of protein intake excreted a higher proportion of ingested InAs as MMA (14.6 vs. 11.6%; p = 0.01) and a lower proportion as DMA (72.3 vs. 77.0%; p = 0.01) than did subjects in the upper quartile of protein intake. Subjects in the lower quartile of iron, zinc, and niacin intake also had higher urinary percent MMA and lower percent DMA levels than did subjects with higher intakes of these nutrients. These associations were also seen in multivariate regression analyses adjusted for age, sex, smoking, and total urinary arsenic. Given the previously reported links between high percent MMA and increased cancer risks, these findings are consistent with the theory that people with diets deficient in protein and other nutrients are more susceptible than others to arsenic-caused cancer.     

长期高砷暴露人群砷甲基化与皮肤损害关系的研究

目的探讨长期高砷暴露人群砷代谢差异与砷致皮肤损害之间的关系。方法随机选取某砷污染村庄常住居民327名,进行问卷调查和体格检查。二乙基二硫代氨基甲酸银比色法检测发总砷含量,离子色谱氢化物发生原子荧光法测定尿中四种砷代谢形态。结果发砷含量总体较高,但不同程度皮肤损害的4组间发砷含量差异无显著性;尿中DMA和MMA浓度随着年龄增加有上升的趋势,且与皮肤损害程度呈显著正相关,而无机砷浓度与皮肤损害未见显著相关;重度组人群尿中MMA相对比例显著高于其它3组,而重度组DMA/MMA比值显著低于对照组和轻度组;MMA比例与皮肤损害程度呈显著正相关,DMA/MMA比值与皮肤损害程度呈显著负相关;男性对砷的蓄积能力高于女性,但对砷的甲基化能力低于女性;40岁以上人群对砷的甲基化能力高于40岁以下成人;吸烟者和饮酒者对砷的甲基化代谢水平分别低于非吸烟者和非饮酒者。结论砷在人体内的甲基化代谢水平受性别、年龄、吸烟和饮酒等多因素影响;砷致皮肤损伤程度与砷在体内的甲基化程度有关。     

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

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

Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh

Chronic exposure to arsenic is occurring throughout South and East Asia due to groundwater contamination of well water. Variability in susceptibility to arsenic toxicity may be related to nutritional status. Arsenic is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via one-carbon metabolism, a biochemical pathway that is dependent on folate. The majority of one-carbon metabolism methylation reactions are devoted to biosynthesis of creatine, the precursor of creatinine. Our objectives of this cross-sectional study were to characterize the relationships among folate, cobalamin, homocysteine, and arsenic metabolism in Bangladeshi adults. Water arsenic, urinary arsenic, urinary creatinine, plasma folate, cobalamin, and homocysteine were assessed in 1,650 adults; urinary arsenic metabolites were analyzed for a subset of 300 individuals. The percentage of DMA in urine was positively associated with plasma folate (r = 0.14, p = 0.02) and negatively associated with total homocysteine (tHcys; r = -0.14, p = 0.01). Conversely, percent MMA was negatively associated with folate (r = -0.12, p = 0.04) and positively associated with tHcys (r = 0.21, p = 0.0002); percent inorganic arsenic (InAs) was negatively associated with folate (r = -0.12, p = 0.03). Urinary creatinine was positively correlated with percent DMA (r = 0.40 for males, p < 0.0001; 0.25 for females, p = 0.001), and with percent InAs (r = -0.45 for males, p < 0.0001; -0.20 for females, p = 0.01). Collectively, these data suggest that folate, tHcys, and other factors involved in one-carbon metabolism influence arsenic methylation. This may be particularly relevant in Bangladesh, where the prevalence of hyperhomocysteinemia is extremely high.     

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

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 (Asinorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (Assum). 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 micro g/g; median urinary Assum, 5.8 microg/L), there was a significant but weak association between As in soil and urinary Assum(r = 0.21, p < 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 Assum values (p < 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p < 0.001). NMSC cases had significantly higher levels of Assum, DMA, and Asinorg. The methylation index Asinorg/(MMA + DMA) was about 20% lower among cases (p < 0.05) and in men (p < 0.05) compared with controls and females, respectively.