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Catalase plays an important role in a genotoxic pathway of methylated arsenicals
Citation:
KLIGERMAN, A. D., J. G. Munz, AND A. H. TENNANT. Catalase plays an important role in a genotoxic pathway of methylated arsenicals. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
Here we determine whether catalase (Cat) is also essential in protecting cells against methylated arsenical exposure
Description:
Arsenic is a common contaminant of drinking water in many parts of the world. Consumption of arsenic-contaminated drinking water has been implicated in both cancerous and non-cancerous health conditions. However, the pathways that lead to arsenic-induced health conditions have not been clearly defined. Previous work in our laboratory demonstrated a key protective role for superoxide dismutase in primary mouse lymphocytes exposed to methylated arsenicals. Here we determine whether catalase (Cat) is also essential in protecting cells against methylated arsenical exposure. Taken together these studies aim to identify an ultimate reactive oxygen species (ROS; O2 or OH) that may be involved in inducing genotoxic damage after arsenic exposure. Cat+/– mice were obtained and bred to produce offspring that were Cat+/+, Cat+/–, and Cat–/–for the Cat gene. Cat+/+: and Cat–/–mouse primary lymphocytes were isolated and exposed to various concentrations of hydrogen peroxide (H2O2) and monomethylarsonousacid (MMA111). We have used the alkaline single-cell electrophoresis assay(comet) to measure genotoxic damage. H2O2 was used as a positive control for ROS and methyl methanesulfonate (MMS), which does not induce DNA damage via oxidative stress, was used as a positive control for genotoxicity. When compared to Cat+/+: cells, an increase in DNA damage (as expressed by tail moment) was observed in Cat–/–-cells when exposed to both H2O 2 (36.3 vs. 44.5) and MMA111(7.0 vs.9.7),but not to MMS(7.7vs.8.9). Our results suggest that MMA111 induces DNA damage via the production of O2 and ·OH. A comparison of catalase activity between liver tissue and lymphocytes showed that the activity in the liver is higher by a factor of approximately 4. Therefore, future studies will determine if catalase offers hepatocytes greater protection from OH than is observed in lymphocytes. [This is an abstract or proposed presentation and does not necessarily reflect EPA policy.]