The role of glutathione and DNA strand break repair in determining the shoulder of the radiation survival curve.

The nonprotein thiol glutathione (GSH) and the rate and extent of repair of DNA strand breaks were investigated as two possible determinants of the size of the shoulder of the X-ray survival curve in Chinese Hamster Ovary (CHO) cells. Both cell survival and DNA single strand break repair were measured at comparable radiation doses (using clonogenic and alkaline elution assays respectively) following treatment of CHO cells with agents which deplete GSH levels and/or reduce the shoulder of the radiation survival curve. CHO cells were treated with diethylmaleate (DEM) at doses which reduce GSH levels from 10% to less than 1% of control values. GSH depletion produced dose-modifying radiosensitization of hypoxic but not aerobic cells, reducing the oxygen enhancement ratio (OER) from 2.6 to 1.7, with no change in the survival curve shoulder, nor in the rate of repair of DNA strand breaks. Since mitotic CHO cells exhibited a reduced shoulder compared to asynchronous cells with no difference in the Do of the survival curve, they provided an opportunity to test the possible association of the shoulder size with the repair rate of DNA breaks. Both mitotic and asynchronous cells had the same initial number of strand breaks for a given radiation dose, but mitotic cells had a half-life for repair of those breaks which was significantly longer.(ABSTRACT TRUNCATED AT 250 WORDS)