Catalase has a key role in protecting cells from the genotoxic effects of monomethylarsonous acid: A highly active metabolite of arsenic

Although it is widely known that arsenic‐contaminated drinking water causes many diseases, arsenic's exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as an important key event in the toxic MOA of arsenic. 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 (H₂O₂). The authors assessed the induction of DNA damage using the Comet assay following exposure of mouse Cat^+/+ and Cat^?/? primary splenic lymphocytes to monomethylarsonous acid (MMA^III) to identify the potential role of H₂O₂ in mediating cellular effects of this metalloid. The results showed that the Cat^?/? lymphocytes are more susceptible to MMA^III than the Cat^+/+ lymphocytes by a small (1.5‐fold) 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 Cat^+/+, Cat^+/?, and Cat^?/? hepatocytes to determine if the Cat^?/? cells were more susceptible to MMA^III than lymphocytes. The results showed that the Cat^?/? hepatocytes exhibit higher levels of DNA strand breakage than the Cat^+/+ (approximately fivefold) and Cat^+/? (approximately twofold) hepatocytes exposed to MMA^III. Electron spin resonance using 5,5‐dimethyl‐1‐pyrroline‐N‐oxide as the spin‐trap agent detected the generation of ·OH via MMA^III when H₂O₂ was present. These experiments suggest that CAT is involved in protecting cells against the genotoxic effects of the ·OH generated by MMA^III. Environ. Mol. Mutagen. 54:317–326, 2013. © 2013 Wiley Periodicals, Inc.