title: The role of biomethylation in toxicity and carcinogenicity of arsenic: a research update.
abstract: Recent research of the metabolism and biological effects of arsenic has profoundly changed our understanding of the role of metabolism in modulation of toxicity and carcinogenicity of this metalloid. Historically, the enzymatic conversion of inorganic arsenic to mono- and dimethylated species has been considered a major mechanism for detoxification of inorganic arsenic. However, compelling experimental evidence obtained from several laboratories suggests that biomethylation, particularly the production of methylated metabolites that contain trivalent arsenic, is a process that activates arsenic as a toxin and a carcinogen. This article summarizes this evidence and provides new data on a) the toxicity of methylated trivalent arsenicals in mammalian cells, b) the effects of methylated trivalent arsenicals on gene transcription, and c) the mechanisms involved in arsenic methylation in animal and human tissues.
authors.affiliation: Department of Pediatrics, Center for Environmental Medicine and Lung Biology, Burnett-Womack Clinical Sciences Building, University of North Carolina, Chapel Hill, NC 27599-7220, USA. styblo@med.unc.edu
authors.forename: Miroslav
authors.initials: M
authors.lastname: Stýblo
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Drobná
authors.forename: Ilona
authors.initials: I
authors.lastname: Jaspers
authors.forename: Shan
authors.initials: S
authors.lastname: Lin
authors.forename: David J
authors.initials: DJ
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001151:Arsenic / Q000378:metabolism* / Q000633:toxicity*; D001711:Biotransformation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006801:Humans; D008322:Mammals; D008745:Methylation; D008780:Methyltransferases / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D008780:Methyltransferases; D001151:Arsenic