UV- irradiation induces oxidative damage to mitochondrial DNA primarily through hydrogen peroxide

PURPOSE: The aim of this study is to investigate further roles of reactive oxygen species (ROS) in oxidative damages of mitochondrial DNA (mtDNA) by UV-irradiation.METHODS: We introduced cDNAs of MnSOD (manganese superoxide dismutase) and/or catalase (CAT) into the human hepatoma cell line, SK-HEP1. After UV-irradiation, purified mtDNA was hydrolyzed and analyzed using HPLC system to determine contents of 8-hydroxy-2\u27-deoxyguanosine (8OHdG), a marker of oxidatively damaged DNA molecule.RESULTS: UV-irradiation induced the accumulation of 8OHdG at a significant higher level in MnSOD-transfectants than in other cell lines. The accumulation of 8OHdG was reduced in cells overexpressing CAT when compared to that in the control cells. Co-overexpression of CAT inhibited the accumulation of 8OHdG in MnSOD-tranfectants and the accumulated levels of 8OHdG were in parallel with those of H2O2.CONCLUSIONS: Our results suggest that H2O2 plays a key role in mtDNA damage in UV-irradiated cells since MnSOD induces and CAT reduces the generation of H2O2. Our results also indicate that the increased activity of MnSOD may lead to a toxic effect on mtDNA by UV-irradiation.第７６会大