Transfection of the superoxide dismutase (SOD) gene for radioprotection

Radiotherapy is limited by normal tissue toxicity. Manganese SOD (MnSOD), is an endogenous antioxidant which catalyses the conversion of superoxide anions to hydrogen peroxide in the initial detoxification of these molecules. Using a three dimensional multicellular tumour spheroid model, we have established that transfection of the MnSOD gene, under the control of the RSV promoter, resulted in increased radioprotection of UVW glioma cells. The surviving fraction after a radiation dosage of 2Gy was 39% for UVW cells and 51 % for MnSOD transfected UVW cells. Insertion of the MnSOD gene in the reverse orientation (UVW SOD-) sensitised UVW cells to radiation. The surviving fraction after a radiation dosage of 2Gy was less than 10% for the reverse orientation construct, suggesting therapeutic possibilities for the expression of this construct in tumour cells. Preliminary studies indicate that antisense SOD transfectants succumb more readily than UVW cells to radiation insult, especially within the low dose (sub-Gray) range. This suggests that the mechanism by which the reverse orientation construct operates may not be the same as a specific antisense construct1(Kuninaka, Ichinose et al. 2000). If the mechanisms by which this phenomenon operates can be elucidated, it may offer the ability, in future, to alter the radioresistance of either tumour or normal body cells. This could therefore increase the differential between tumour and normal cells which is so crucial to efficient radiotherapy. References I. Kuninaka, S., Y. Ichinose, et al. (2000). "Suppression of manganese superoxide dismutase augments sensitivity to radiation, hyperthermia and doxorubicin in colon cancer cell lines by inducing apoptosis." Br J Cancer 83(7): 928-34.