| Abstrakt: |
Arsenic methyltransferase (As3mt) catalyzes the conversion of inorganic arsenic (iAs) to its methylated metabolites, including toxic methylarsonite (MAs III ) and dimethylarsinite (DMAs III ). Knockout (KO) of As3mt was shown to reduce the capacity to methylate iAs in mice. However, no data are available on the oxidation states of As species in tissues of these mice. Here, we compare the oxidation states of As species in tissues of male C57BL/6 As3mt -KO and wild-type (WT) mice exposed to arsenite (iAs III ) in drinking water. WT mice were exposed to 50 mg/L As and As3mt -KO mice that cannot tolerate 50 mg/L As were exposed to 0, 15, 20, 25 or 30 mg/L As. iAs III accounted for 53% to 74% of total As in liver, pancreas, adipose, lung, heart, and kidney of As3mt -KO mice; tri- and pentavalent methylated arsenicals did not exceed 10% of total As. Tissues of WT mice retained iAs and methylated arsenicals: iAs III , MAs III and DMAs III represented 55%‐68% of the total As in the liver, pancreas, and brain. High levels of methylated species, particularly MAs III , were found in the intestine of WT, but not As3mt -KO mice, suggesting that intestinal bacteria are not a major source of methylated As. Blood of WT mice contained significantly higher levels of As than blood of As3mt -KO mice. This study is the first to determine oxidation states of As species in tissues of As3mt -KO mice. Results will help to design studies using WT and As3mt -KO mice to examine the role of iAs methylation in adverse effects of iAs exposure. [ABSTRACT FROM AUTHOR] |
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