ENZYMATIC METHYLATION OF ARSENIC COMPOUNDS .4. IN-VITRO AND IN-VIVO DEFICIENCY OF THE METHYLATION OF ARSENITE AND MONOMETHYLARSONIC ACID INTHE GUINEA-PIG

Using an in vitro as say which measures the transfer of a radiolabeled methyl moiety of S-[methyl-H-3]adenosylmethionine ([H-3]SAM) to arsen ite or monomethylarsonate (MMA) to yield [methyl-H-3]MMA or [methyl-H- 3]dimethylarsinate (DMA) respectively, guinea pig liver cytosol was fo und to be deficient in the enzyme activities which methylate these sub strates. Moreover, when guinea pigs were given a single intraperitonea l dose of [As-73]arsenate (400 mu g/kg body weight, 25 mu Ci/kg body w eight), very little or no methylated arsenic species were detected in the urine after cation exchange chromatography. The urine collected 0- 12 h after arsenate injection contained 98% inorganic arsenic and less than 1% DMA. No MMA was detected in the 0-12 h urine. Urine collected 12-24 h after injection contained approximately 93% inorganic arsenic , 2% MMA and 3% DMA in five of the six animals studied. However, in th e 12-24 h urine of one guinea pig, 17% of the radioactivity was DMA, 8 0% was inorganic arsenic and 3% was MMA. The guinea pig, like the marm oset and tamarin monkeys and unlike most other animals studied thus fa r, appears to be deficient as far as the enzyme activities that methyl ate inorganic arsenite. The results of these experiments suggest that there may be a genetic polymorphism associated with the enzymes that m ethylate inorganic arsenite.