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Catalase can protect cells against the genotoxic effects of monomethylarsonous acid
Citation:
MUNIZ ORTIZ, J. G., K. WALLACE, AND A. D. KLIGERMAN. Catalase can protect cells against the genotoxic effects of monomethylarsonous acid. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
Although it is widely known that arsenic-contaminated drinking water causes cancer and other health effects, its exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as a key event in the MOA of arsenic.
Description:
Although it is widely known that arsenic-contaminated drinking water causes cancer and other health effects, its exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as a key event in the MOA of arsenic. Our studies are centered on identifying a reactive oxygen species involved in the genotoxicity of arsenic using a catalase (Cat) knock-out mouse model, which is impaired in its ability to break down hydrogen peroxide (H202) that leads to an increase in hydroxyl radicals (•OH). We assessed the induction of DNA damage using the comet assay following exposure to monomethylarsonous acid (MMAIII) of Cat+/+ and Cat–/– primary lymphocytes to identify the potential role of H202 in mediating cellular effects of this metalloid. Our results showed that the Cat–/– lymphocytes are more susceptible to DNA damage following exposure to MMAIII than the Cat+/+ lymphocytes by a small (1.49-fold), but statistically significant difference. Cat activity assays demonstrated that liver tissue has ~3 times more Cat activity than lymphocytes. Therefore, comet assays were performed on primary Cat+/+, Cat+/–, and Cat–/– hepatocytes to determine if the Cat–/– hepatocytes were more susceptible to MMA11I than lymphocytes, Results with the comet assay showed that the Cat–/– hepatocytes exhibit higher levels of DNA strand breakage than did Cat+/+ and Cat+/– hepatocytes exposed to MMAIII. Our experiments suggest that Cat is involved in protecting cells against MMAIII-generated H202, and that •OH might be involved in its genotoxicity pathway. Furthermore, individuals afflicted with genetic polymorphisms in their Cat gene could exhibit altered susceptibility to arsenic toxicity. [This is an abstract or proposed presentation and does not necessarily reflect EPA policy.]