Investigation of Genotoxic and Cytotoxic Effects of Hydrogen Peroxide(The Importance of DNA Repair in Oxidative Stress)

Abstract

Oxidative stress-induced reactive oxygen species induce DNA damages that may result in cell death and DNA mutations. In this study, a genotoxic and cytotoxic potential of hydrogen peroxide as a ROS generator, and the effect of cell repair of oxidative stress in TK6 cells were investigated by in vitro micronucleus assay. Cell repair was inhibited by using cytosine earabinoside. Cellular responses to different concentrations of hydrogen peroxide were evaluated by generating dose-response curves. The incidence of increased MN concentrations due to increased H2O2concentrations did not allow the identification of a plateau region. A similar curve pattern was also observed with the repair inhibited group. However, damage caused by H2O2was significantly higher (p<0.001) in the cells with repair inhibition. This demonstrates the importance of DNA repair in the observation of oxidative stress. Proliferative indexes did not change due to increasing H2O2 concentrations in both groups. But the curve of repair inhibited cells was significantly higher (p<0.001) than the curve of repair efficient cells. BN and multinucleate cell counts showed decreases with increasing ROS levels generated by H2O2. But these decreases were not reflected in proliferative index scores. This may be due to H2O2-induced apoptosis, which results in the overestimation of PI values in increasing H2O2concentrations.