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The authors' studies are centered on identifying a reactive species involved in the genotoxicity of arsenic using a catalase (CAT) knockout mouse model that is impaired in its ability to breakdown hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>). The authors assessed the induction of DNA damage using the Comet assay following exposure of mouse <jats:italic>Cat<jats:sup>+\/<\/jats:sup><jats:sup>+<\/jats:sup><\/jats:italic> and <jats:italic>Cat<\/jats:italic><jats:sup>\u2212<\/jats:sup><jats:italic><jats:sup>\/<\/jats:sup><\/jats:italic><jats:sup>\u2212<\/jats:sup> primary splenic lymphocytes to monomethylarsonous acid (MMA<jats:sup>III<\/jats:sup>) to identify the potential role of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> in mediating cellular effects of this metalloid. The results showed that the <jats:italic>Cat<\/jats:italic><jats:sup>\u2212<\/jats:sup><jats:italic><jats:sup>\/<\/jats:sup><\/jats:italic><jats:sup>\u2212<\/jats:sup> lymphocytes are more susceptible to MMA<jats:sup>III<\/jats:sup> than the <jats:italic>Cat<jats:sup>+\/<\/jats:sup><jats:sup>+<\/jats:sup><\/jats:italic> lymphocytes by a small (1.5\u2010fold) but statistically significant difference. CAT activity assays demonstrated that liver tissue has approximately three times more CAT activity than lymphocytes. Therefore, Comet assays were performed on primary <jats:italic>Cat<jats:sup>+\/<\/jats:sup><jats:sup>+<\/jats:sup><\/jats:italic>, <jats:italic>Cat<jats:sup>+\/<\/jats:sup><\/jats:italic><jats:sup>\u2212<\/jats:sup>, and <jats:italic>Cat<\/jats:italic><jats:sup>\u2212<\/jats:sup><jats:italic><jats:sup>\/<\/jats:sup><\/jats:italic><jats:sup>\u2212<\/jats:sup> hepatocytes to determine if the <jats:italic>Cat<\/jats:italic><jats:sup>\u2212<\/jats:sup><jats:italic><jats:sup>\/<\/jats:sup><\/jats:italic><jats:sup>\u2212<\/jats:sup> cells were more susceptible to MMA<jats:sup>III<\/jats:sup> than lymphocytes. The results showed that the <jats:italic>Cat<\/jats:italic><jats:sup>\u2212<\/jats:sup><jats:italic><jats:sup>\/<\/jats:sup><\/jats:italic><jats:sup>\u2212<\/jats:sup> hepatocytes exhibit higher levels of DNA strand breakage than the <jats:italic>Cat<jats:sup>+\/<\/jats:sup><jats:sup>+<\/jats:sup><\/jats:italic> (approximately fivefold) and <jats:italic>Cat<jats:sup>+\/<\/jats:sup><\/jats:italic><jats:sup>\u2212<\/jats:sup> (approximately twofold) hepatocytes exposed to MMA<jats:sup>III<\/jats:sup>. Electron spin resonance using 5,5\u2010dimethyl\u20101\u2010pyrroline\u2010<jats:italic>N<\/jats:italic>\u2010oxide as the spin\u2010trap agent detected the generation of \u00b7OH via MMA<jats:sup>III<\/jats:sup> when H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> was present. These experiments suggest that CAT is involved in protecting cells against the genotoxic effects of the \u00b7OH generated by MMA<jats:sup>III<\/jats:sup>. Environ. Mol. Mutagen. 54:317\u2013326, 2013. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/em.21780","type":"journal-article","created":{"date-parts":[[2013,5,3]],"date-time":"2013-05-03T09:46:29Z","timestamp":1367574389000},"page":"317-326","source":"Crossref","is-referenced-by-count":7,"title":["Catalase has a key role in protecting cells from the genotoxic effects of monomethylarsonous acid: A highly active metabolite of arsenic"],"prefix":"10.1002","volume":"54","author":[{"given":"Jorge G.","family":"Mu\u00f1iz Ortiz","sequence":"first","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen A.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Integrated Systems Toxicology Division National Health and 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