Combined effect of misonidazole and glutathione depletion by buthionine sulphoximine on cellular radiation response.

Chinese hamster cells (V79) and glutathione-proficient (GSH+/+) and glutathione-deficient (GSH-/-) human fibroblasts were treated with a glutathione (GSH)-depleting agent buthionine sulphoximine (BSO) and the hypoxic radiosensitizer misonidazole (MISO), separately or in combination. Subsequently, the cells were exposed to X-rays. Determination of the yield of single-strand DNA breaks (ssb) immediately after irradiation indicated no effect of BSO or MISO treatment when radiation exposure was made aerobically. Assuming that ssb determined immediately after irradiation reflects mainly the effect of radical processes, the results obtained with BSO and MISO, singly and in combination, agreed well with the predictions of a modified version of the 'competition model' using V79 and GSH+/+ cells. Some results obtained with GSH-/- cells could not be so explained.