Variation in human metabolism of arsenic

Inorganic arsenic is methylated to methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by alternating reduction of AsV to AsIII and addition of a methyl group from S-adenosylmethionine. The methylated metabolites are less reactive with tissue constituents and more readily excreted in the urine than is inorganic arsenic. Therefore, a low percentage of MMA + DMA in urine correlates with a low rate of excretion of the absorbed arsenic. Although most studies indicate on average 10-30% inorganic arsenic, 10-20% MMA, and 60-70% DMA in urine, there seems to be a polymorphism in arsenic methylation. Our studies on arsenic-exposed native Andean people in north-west Argentina, show only a few percent MMA in the urine, which in most other populations is a rare event, occurring in a few individuals only. However, in several other mammalian species this is a common feature. On the other hand, one study indicates a higher than usual % MMA in the urine of arsenic exposed people in Taiwan. There is also a marked intra-individual variation in the urinary pattern of arsenic metabolites. In experimental studies we have shown that the methylation of arsenic is influenced by the form of arsenic absorbed, the dose level, route of exposure, and nutritional status. Our studies in Argentina indicate that arsenic methylation is influenced by age, dose level and, probably, hormonal status. For example, in children there was a lower % DMA in urine compared to adults, and an increasing % DMA with increasing exposure level.