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 (H
2O
2). 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 H
2O
2 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 H
2O
2 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.
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