METHYLATION STUDY OF A POPULATION ENVIRONMENTALLY EXPOSED TO ARSENIC IN DRINKING-WATER

Methylation is considered the detoxification pathway for inorganic ars enic (InAs), an established human carcinogen. Urinary speciation analy sis is used to assess the distribution of metabolites [monomethylarson ate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], a s indicators of methylation capacity. We conducted a large biomarker s tudy in northern Chile of a population chronically exposed to high lev els of arsenic in drinking water. We report the results of the methyla tion study, which focused on the effects of exposure and other variabl es on the percent InAs, MMA, DMA, and the ratio of MMA. to DMA in urin e. The study consisted of 122 people in a town with arsenic water leve ls around 600 mu g/l and 98 participants in a neighboring town with ar senic levels in water of about 15 mu g/l. The corresponding mean urina ry arsenic levels were 580 mu g/l and 60 mu g/l, of which 18.4% and 14 .9% were InAs, respectively. The main differences were found for MMA:D MA; exposure, smoking, and being male were associated with higher MMA: DMA, while longer residence, Atacameno ethnicity, and being female wer e associated with lower MMA:DMA. Together, these variables explained a bout 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 tha n those attributed to the variables investigated. The differences in p ercent inks were small and within the ranges of other studies of backg round exposure levels. The biological significance of MMA:DMA, which w as more than 1.5 times greater in the exposed group, and its relations hip to sex, length of exposure, and ethnicity need further investigati on because its relevance to health risk is not clear.