Enzymatic methylation of arsenic compounds. IX. Liver arsenite methyltransferase and arsenate reductase activities in primates.
Inorganic arsenic is an important environmental toxicant of both natural and anthropogenic sources. It is a human carcinogen for which appropriate animal models of most arsenic-induced cancers are missing. Although methylation of inorganic arsenic has been considered its primary mechanism for detoxification, the results of recent investigations disagree. We have investigated 17 species of non-human primates, including great apes, New and Old World monkeys and prosimians, and have found that thirteen of them lacked hepatic arsenite methyltransferase activity in vitro. Four primate species, three from the Old World genus Macaca, and one of three animals from the New World genus Saimiri, had arsenite methyltransferase activity. That all the tissues examined were viable was demonstrated by their all having arsenate reductase activity. These data suggest that methylation of inorganic arsenic is not a detoxification mechanism for many non-human primates. Thus, alternative methods of detoxifying inorganic arsenic in mammals need to be considered and investigated. In addition, there appears to be a phylogenetic component to having arsenite methyltransferase activity, as evidenced by the result of our study of the Macaca species.
Wildfang
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Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85721, USA.
Radabaugh
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Vasken Aposhian
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D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001151:Arsenic / Q000652:urine; D001152:Arsenicals / Q000378:metabolism*; D053501:Arsenite Transporting ATPases; D003600:Cytosol / Q000201:enzymology; D016623:Ion Pumps; D008099:Liver / Q000201:enzymology*; D008780:Methyltransferases / Q000378:metabolism*; D009097:Multienzyme Complexes; D011323:Primates / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D001152:Arsenicals; D016623:Ion Pumps; D009097:Multienzyme Complexes; D013438:Sulfhydryl Compounds; D008780:Methyltransferases; C116338:arsenite methyltransferase; D000251:Adenosine Triphosphatases; D053501:Arsenite Transporting ATPases; D001151:Arsenic