TOXI 103 |
| A striking feature of inorganic arsenic metabolism is its conversion to methylated arsenicals. Intermediates and products formed in this pathway are likely to mediate some toxic and carcinogenic effects which are ascribed to inorganic arsenic. Elucidating this pathway involves development of analytical techniques needed to identify each arsenical and examination of biological processes involved in metabolite formation. For example, one enzyme, arsenic (+3 oxidation state) methyltransferase (AS3MT), catalyzes a series of coupled reactions in which arsenicals are oxidatively methylated and reduced, forming a pathway from arsenite to its ultimate metabolite, trimethylarsine. AS3MT's catalytic activity depends on cellular reductants (e.g., thioredoxin and glutathione) and is affected by common polymorphisms. Understanding the roles of cellular reductants and of genetic variation in control of AS3MT activity provides a more complete picture of linkage between the metabolism of arsenicals and their toxic and carcinogenic effects. (Abstract does not reflect US EPA policy). |
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Metal Carcinogenesis: New Concepts
2:00 PM-5:00 PM, Wednesday, 13 September 2006 Moscone Center -- Room 308, Oral
Division of Chemical Toxicology |