title: Arsenic (+ 3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis.
abstract: Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+ 3 oxidation state) methyltransferase (As3mt) yielding mono-, di-, and trimethylated arsenicals. To investigate the evolution of molecular mechanisms that mediate arsenic biotransformation, a comparative genomic approach focusing on the invertebrate chordate Ciona intestinalis was used. Bioinformatic analyses identified an As3mt gene in the C. intestinalis genome. Constitutive As3mt RNA expression was observed in heart, branchial sac, and gastrointestinal tract. Adult animals were exposed to 0 or 1 ppm of iAs for 1 or 5 days. Steady-state As3mt RNA expression in the gastrointestinal tract was not modulated significantly by 5 days of exposure to iAs. Tissue levels of iAs and its methylated metabolites were determined by hydride generation-cryotrapping-gas chromatography-atomic absorption spectrometry. At either time point, exposure to iAs significantly increased concentrations of iAs and its methylated metabolites in tissues. After 5 days of exposure, total speciated arsenic concentrations were highest in branchial sac (3705 ng/g), followed by heart (1019 ng/g) and gastrointestinal tract (835 ng/g). At this time point, the sum of the speciated arsenical concentrations in gastrointestinal tract and heart equaled or exceeded that of iAs; in branchial sac, iAs was the predominant species present. Ciona intestinalis metabolizes iAs to its methylated metabolites, which are retained in tissues. This metabolic pattern is consistent with the presence of an As3mt ortholog in its genome and constitutive expression of the gene in prominent organs, making this basal chordate a useful model to examine the evolution of arsenic detoxification.
authors.affiliation: Pharmacokinetics Branch, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. thomas.david@epa.gov
authors.forename: David J
authors.initials: DJ
authors.lastname: Thomas
authors.forename: Gerardo M
authors.initials: GM
authors.lastname: Nava
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Cai
authors.forename: James L
authors.initials: JL
authors.lastname: Boyer
authors.forename: Araceli
authors.initials: A
authors.lastname: Hernández-Zavala
authors.forename: H Rex
authors.initials: HR
authors.lastname: Gaskins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018053:Arsenites / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation; D001934:Branchial Region / Q000201:enzymology; D002849:Chromatography, Gas; D002938:Ciona intestinalis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D030541:Databases, Genetic; D019143:Evolution, Molecular; D041981:Gastrointestinal Tract / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D017670:Sodium Compounds / Q000378:metabolism* / Q000633:toxicity; D013054:Spectrophotometry, Atomic; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000378:metabolism* / Q000633:toxicity
chemical_list: D018053:Arsenites; D012333:RNA, Messenger; D017670:Sodium Compounds; D014874:Water Pollutants, Chemical; C017947:sodium arsenite; D008780:Methyltransferases