Factors influencing arsenic methylation in humans

Most mammals metabolize inorganic arsenic to methylarsonic acid (MMA) and d imethylarsinic acid (DMA) by stepwise transfer of methyl groups from S-aden osylmethionine to arsenic in its trivalent oxidation state. The methylated metabolites are less reactive with tissue components, less toxic, and more readily excreted in the urine than is inorganic arsenic. There are marked d ifferences in arsenic metabolism between mammalian species and between huma n population groups and individuals. We are studying arsenic metabolism in people of native Andean origin or mixed ethnic origin exposed to arsenic in drinking water (200 mu g As/L) in northern Argentina. These people have a unique metabolism of arsenic in that they excrete only a few percent MMA in the urine. All other population groups studied so far have an average urin ary metabolite distribution of inorganic arsenic, MMA, and DMA of about 20: 15:65. However, the interindividual variation is extensive. This may indica te the existence of genetic polymorphism in the expression of arsenic methy ltransferases. The toxicological significance of the observed differences i n formation of MMA and DMA is not clear. In the populations studied, arsenic methylation was influenced by age, expo sure level, and pregnancy. The relative percentage of urinary DMA was lower in children than in adults, which may indicate that children retain more a rsenic in their tissues and, therefore, are more sensitive to arsenic expos ure. In the children, there was an increase in % DMA with increasing exposu re level, indicating an induction of the methylation of arsenic. Previous s tudies on adult populations in Chile and Mexico indicate a decrease in the relative amount of DMA in urine and a corresponding increase in inorganic a rsenic and MMA, with increasing exposure levels. In the Argentinean populat ion groups, arsenic was shown to be transferred to the fetus, in line with previously published data from experimental animal studies. There was a mar ked increase in the relative amount of DMA in urine at the end of pregnancy , as well as in the newborn infant, indicating induction of arsenic methyla tion during pregnancy. J. Trace Elem. Exp. Med. 13:173-184, 2000. (C) 2000 Wiley-Liss, Inc.