title: Oxidation state specific analysis of arsenic species in tissues of wild-type and arsenic (+3 oxidation state) methyltransferase-knockout mice.
abstract: Arsenic methyltransferase (As3mt) catalyzes the conversion of inorganic arsenic (iAs) to its methylated metabolites, including toxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII). Knockout (KO) of As3mt was shown to reduce the capacity to methylate iAs in mice. However, no data are available on the oxidation states of As species in tissues of these mice. Here, we compare the oxidation states of As species in tissues of male C57BL/6 As3mt-KO and wild-type (WT) mice exposed to arsenite (iAsIII) in drinking water. WT mice were exposed to 50mg/L As and As3mt-KO mice that cannot tolerate 50mg/L As were exposed to 0, 15, 20, 25 or 30mg/L As. iAsIIIaccounted for 53% to 74% of total As in liver, pancreas, adipose, lung, heart, and kidney of As3mt-KO mice; tri- and pentavalent methylated arsenicals did not exceed 10% of total As. Tissues of WT mice retained iAs and methylated arsenicals: iAsIII, MAsIIIand DMAsIIIrepresented 55%-68% of the total As in the liver, pancreas, and brain. High levels of methylated species, particularly MAsIII, were found in the intestine of WT, but not As3mt-KO mice, suggesting that intestinal bacteria are not a major source of methylated As. Blood of WT mice contained significantly higher levels of As than blood of As3mt-KO mice. This study is the first to determine oxidation states of As species in tissues of As3mt-KO mice. Results will help to design studies using WT and As3mt-KO mice to examine the role of iAs methylation in adverse effects of iAs exposure.
authors.affiliation: Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: jenna.currier@gmail.com.
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Currier
authors.affiliation: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Christelle
authors.initials: C
authors.lastname: Douillet
authors.affiliation: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Drobná
authors.affiliation: Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: styblo@med.unc.edu.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Stýblo
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001152:Arsenicals / Q000494:pharmacology*; D008297:Male; D008780:Methyltransferases; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D001152:Arsenicals; D014874:Water Pollutants, Chemical; D008780:Methyltransferases; D001151:Arsenic
keywords: Arsenic (+3 oxidation state) methyltransferase; Arsenic speciation analysis; As3mt knockout mice; Hydride generation-cryotrapping-atomic absorption spectrometry