The effect of methyltransferase inhibition on the metabolism of [74As]arsenite in mice and rabbits.

The effect of periodate-oxidized adenosine (PAD), an inhibitor of certain methyltransferases, on the biotransformation and tissue retention of [74As]arsenite in mice and rabbits was studied. Injection of PAD (100 mumol/kg body wt.), 15-min prior to the injection of [74As]arsenite (0.4 mg As/kg body wt.), resulted in a 25-70% decrease in the production of [74As]dimethylarsinic acid ( [74As]DMA). This implies that S-adenosylmethionine is the methyl-donor in the methylation of inorganic arsenic in vivo. Due to interaction of the unmethylated arsenite with tissue constituents the PAD-treated animals had significantly higher (2-6 times) tissue concentrations of 74As than did the controls. This effect was first observed in the liver, indicating that this organ is the main site of the methylation of arsenic. The increase in the tissue retention due to the PAD-treatment remained also after cessation of the inhibition of methylation. The results can be seen as confirmation that alkylation of inorganic arsenic acts as a detoxification mechanism in mammals.