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 car cinogen, undergoes bio-methylation to monomethylarsonate (MMA) and dim ethylarsinate (DMA). It has been proposed that saturation of methylati on capacity at high exposure levels may lead to a threshold for the ca rcinogenicity of In-As. The relative distribution of urinary In-As, MM A, and DMA is used as a measure of human methylation capacity. The mos t common pathway for elevated environmental exposure to In-As worldwid e is through drinking water. We conducted a biomarker study in norther n Chile of a population chronically exposed to water naturally contami nated with high arsenic-content (600 mu g/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 mu g/l) for 2 m onths. The proportions of In-As, MMA, and DMA in urine were compared b efore and after intervention, and the effect of other factors on the d istribution of arsenic metabolites was also analyzed. The findings of this study indicate that the decrease in arsenic exposure was associat ed 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 suc h as smoking, gender, age, years of residence, and ethnicity were asso ciated 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 cha nges observed in the percent In-As and in the MMA/DMA ratio do not sup port an exposure-based threshold for arsenic methylation in humans.