Changeinradiation sensitivityby mitochondrial damageand their mechanisms

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We observed previously that mitochondria DNA-less (Rho 0) cells are much more sensitive to radiation in terms of the radiationsensitivity (colony assay), apoptosis (Hoechst stain), DNA double strand breaks, and chromosome aberrations. An other finding is that Rho 0 cells contain much less amount of manganese superoxidedismutase (MnSOD) in themitochondria. A transfection vector containing MnSOD was made and was transfected to the Rhocells, and the change in apoptosis frequency was observed. The results showed that frequency of apoptosis by X-irradiation was decreased compared to that in the non-transfected cells, suggesting the MnSOD is a factor to determine the radiation sensitivity. These results indicate that changes in mitochondrial factors play an important key-role in determination of the radiation sensitivity. These evidences were also confirmed by transfecting to an other cell line, HLE, a hepatocarcinoma cell line, by transfecting the MnSOD gene containingvectors. These results suggest that change in superoxide levels in mitochondria is an important factor to determine the cellular radiation sensitivity.