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

Abstract

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.Imagesp620-aFigure 1.Figure 2.Figure 2.Figure 2.Figure 2.

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

“…It is worth mentioning, however, that MMA has the highest correlation coefficient among the metabolites. MMA excretion has been associated with an increased risk of arsenic-related diseases such as bladder and skin cancer (Hopenhayn-Rich et al, 1996;Chen et al, 2003;Steinmaus et al, 2006). This information supports the hypothesis that arsenic drinking water concentrations are, to some extent, good surrogates of arsenic exposure, even in populations exposed to relatively low levels of arsenic in drinking water (o50 mg/l).…”

Arsenic in the human food chain, biotransformation and toxicology – Review focusing on seafood arsenic

“…For instance, increased presence of MA (III) in urine of a Mexican population chronically exposed to iAs in drinking water was associated with a greater risk of As-induced skin lesions [60]. Studies of populations chronically exposed to iAs from drinking water have shown that the relative proportion of urinary MA may increase with increasing dose of iAs exposure [86,87,170,171]. Higher urinary MA associated with increased exposure of iAs in drinking water, has been proposed to be a result of the inhibition of the second methylation step [172].…”

“…A high proportion of MA in urine may indicate lower methylation capacity. Age, smoking and gender seem to influence the relative distribution of methylated urinary arsenicals [85][86][87].…”

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

“…If the MMA/DMA ratio is high, there is poor methylation at the second step. Population studies have demonstrated that generally the relative distribution is in the range of 10-30% InAs, 10-20% MMA, and 60-80% DMA in populations exposed to arsenic (2,13). There is an emerging hypothesis that methylated forms of arsenic may play a larger role in arsenic toxicity (14).…”