Glutathione peroxidase compensates for the hypersensitivity of Cu,Zn-superoxide dismutase overproducers to oxidant stress.

The balance between several components of the antioxidant defenses appears to be important for the cellular resistance to oxidative stress. While Cu,Zn-superoxide dismutase (SOD) transfectants of mouse epidermal cells JB6 clone 41 were sensitized to oxidants produced by xanthine/xanthine oxidase (X/XO) consecutive transfection with catalase corrected their hypersensitivity (Amstad, P., Peskin, A., Shah, G., Mirault, M. E., Moret, R., Zbinden, I., and Cerutti, P. (1991) Biochemistry 30, 9305-9313). We studied the effect of the transfection of bovine selenoglutathione peroxidase (GPx) on the sensitivity of JB6 clone 41 and its SOD transfectants. Sensitivity to DNA strand breakage and killing by X/XO was reversely related to the activity ratios GPx over SOD. A GPx-transfectant of JB6 clone 41 cells with a GPx/SOD ratio of 3.8 was very strongly protected. The hypersensitivity of the SOD clones with GPx/SOD ratios of 0.4 was corrected or overcorrected by secondary transfection with bovine Se-GPx resulting in increased activity ratios GPx/SOD of 1 to 2.4. Our results indicate that small deviations from the physiological activity ratios of GPx/SOD have a dramatic effect on the resistance of cells to oxidant-induced damage to the genome and cell killing.