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Do Superoxide Dismutase (SOD) and Catalase (CAT) protect Cells from DNA Damage Induced by Active Arsenicals?
KLIGERMAN, A. D., A. H. TENNANT, AND J. Muniz-Ortiz. Do Superoxide Dismutase (SOD) and Catalase (CAT) protect Cells from DNA Damage Induced by Active Arsenicals? Presented at Environmental Mutagen Society Annual Meeting, Fort Worth, TX, October 23 - 27, 2010.
This presentation gives strong evidence that reactive oxygen species are involved in the DNA damage caused bv reactive arsenicals. It also shows that superoxide IS either directly or indirectly involved in this process, and that the genotype of cells can offer protection against this.
Superoxide dismutase (SOD) catalyzes the conversion of superoxide to hydrogen peroxide, which can be converted to water and oxygen through the action of catalase. Heterozygous mice of strain B6: 129S7-SodltmlLeb/J were obtained from Jackson Laboratories and bred to produce offspring that were heterozygous (+/Sod Itml Leb), homozygous wild-type (+1+), and homozygous knockout (SodltmlLeb /SodltmIl.eb ) for the Cu/Zn superoxide dismutase ( Sod l ) gene. Splenocytes from these mice were exposed to several concentrations of either sodium arsenite (As3 [0-200 11M)), monomethylarsonous acid (MMA3 [0-10 11M)), or dimethylarsinous acid (DMA3 [0-10 11M)) for 2 hours. Cells were then examined for DNA damage using the alkaline single cell gel electrophoresis assay. Methyl methanesulfonate (MMS) was used as a positive control. Splenocytes from each of the 3 genotypes for Sodl were equally sensitive to MMS and As3. However, at equimolar concentrations DMA3 and NlMA3 produced significantly more DNA damage in the homozygous knock-out mouse splenocytes than in the splenocytes from the wild-type or heterozygous mice. These findings suggest that superoxide is involved either directly or indirectly in producing DNA damage in cells exposed to trivalent methylated arsenicals. Additional studies will be presented on data obtained from catalase knock-out mice to determine if the peroxide radical is also involved in arsenic-induced DNA damage. [This abstract does not necessarily reflect EPA policy.]
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
GENETIC AND CELLULAR TOXICOLOGY BRANCH