title: Methylation of inorganic arsenic by murine fetal tissue explants.
abstract: Although it is generally believed that the developing fetus is principally exposed to inorganic arsenic and the methylated metabolites from the maternal metabolism of arsenic, little is known about whether the developing embryo can autonomously metabolize arsenic. This study investigates inorganic arsenic methylation by murine embryonic organ cultures of the heart, lung, and liver. mRNA for AS3mt, the gene responsible for methylation of arsenic, was detected in all embryonic tissue types studied. In addition, methylated arsenic metabolites were generated by all three tissue types. The fetal liver explants yielded the most methylated arsenic metabolites (∼7% of total arsenic/48 h incubation) while the heart, and lung preparations produced slightly greater than 2% methylated metabolites. With all tissues the methylation proceeded mostly to the dimethylated arsenic species. This has profound implications for understanding arsenic-induced fetal toxicity, particularly if the methylated metabolites are produced autonomously by embryonic tissues.
authors.affiliation: a Department of Pharmacology and Toxicology , Molecular and Cellular Biology, Bio5 Institute, and Southwest Environmental Health Sciences Center, University of Arizona , Tucson , AZ , USA.
authors.forename: Derrick
authors.initials: D
authors.lastname: Broka
authors.affiliation: a Department of Pharmacology and Toxicology , Molecular and Cellular Biology, Bio5 Institute, and Southwest Environmental Health Sciences Center, University of Arizona , Tucson , AZ , USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Ditzel
authors.affiliation: a Department of Pharmacology and Toxicology , Molecular and Cellular Biology, Bio5 Institute, and Southwest Environmental Health Sciences Center, University of Arizona , Tucson , AZ , USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Quach
authors.affiliation: a Department of Pharmacology and Toxicology , Molecular and Cellular Biology, Bio5 Institute, and Southwest Environmental Health Sciences Center, University of Arizona , Tucson , AZ , USA.
authors.forename: Todd D
authors.initials: TD
authors.lastname: Camenisch
mesh_terms: D000818:Animals; D018053:Arsenites / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000196:embryology; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D009924:Organ Culture Techniques; D017670:Sodium Compounds / Q000378:metabolism* / Q000633:toxicity
chemical_list: D018053:Arsenites; D017670:Sodium Compounds; C017947:sodium arsenite; D008780:Methyltransferases; C116338:arsenite methyltransferase
keywords: Arsenicals; development; metabolism