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Superoxide Dismutase Protects Cells from DNA Damage Induced by Trivalent Methylated Arsenicals
Citation:
TENNANT, A. H. AND A. D. KLIGERMAN. Superoxide Dismutase Protects Cells from DNA Damage Induced by Trivalent Methylated Arsenicals. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS. John Wiley & Sons, Inc, Hoboken, NJ, 52(3):238-243, (2011).
Impact/Purpose:
Arsenic is a human carcinogen, yet we still do not know how arsenic induces cancer. One way to investigate how arsenic induces cancer is to determine how arsenic induces genetic damage, a key event in cancer induction. By exploring how antioxidant defense mechanisms, such as superoxide dismutase, affects the induction of DNA from arsenic, we may be able to understand how arsenic induces cancer and how carcinogenic or other toxic effects of arsenic may be prevented.
Description:
Superoxide dismutase (SOD) catalyzes the conversion of superoxide to hydrogen peroxide. Heterozygous mice of strain B6; 129S7-Sod1(tm1Leb)/J were obtained from Jackson Laboratories and bred to produce offspring that were heterozygous (+/Sod1(tm1Leb)), homozygous wild-type (+/+), and homozygous knockout (Sod1 (tm1Leb/Sod1(tm1Leb )) for the CU/Zn superoxide dismutase ( Sod1) gene. Splenocytes from these mice were exposed to several concentrations of either sodium arsenite (As3 [0-200 uMD], monomethylarsonous acid (MMA3 [0-10 uM]), or dimethylarsinous acid (DMA3 [0-10 uM]) 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 Sod1 were equally sensitive to MMS and As3. However, at equimolar concentrations DMA3 and MMA3 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. These arsenicals may generate reactive oxygen species that damage DNA that could be a key event in cancer initiation.
