Modification of the Response to Actinomycin D-induced Sublethal Damage by Simultaneous Recovery from Potentially Lethal Damage in Mammalian Cells1

conditions after single drug on irradiation treatments (3, 22). Conditions that are suboptimal for growth, such as low temperature, inhibition of protein synthesis, and mainte nance of cells in nutritionally depleted medium, have been reported as favoring recovery from PLO (3, 5, 14, 19, 22, 29). Recovery from PLO occurs in vivo and in vitro (3, 16, 24) in dividing and nondividing mammalian cells (3, 15, 19), in oxic and hypoxic cells (14), and independently of me covery from SLD (3, 14, 19). Conversely, the expression of PLO is measured by a decrease in survival, usually under conditions that inhibit DNA synthesis (22). The CHO cells used in our studies are able to recover from bleomycmn-mnducedPLO (3). The incubation period between SLD-fnactionated dose treatments exactly mimics that used to test for recovery from PLO, and the resulting data sug gest that part of the recovery from SLD observed after frac tionated dose treatments with bleomycin was due to me coveny from PLD (3). It has been reported (10) that the Chinese hamster cell line V79-753B exhibits an increase in survival after ex posume to fractionated doses of AMO. It was suggested, however, that the rise in survival was possibly due to cells progressing into less sensitive stages of the cell cycle by the time the 2nd dose of AMO was administered and not to recovery from SLD. The experiments that we report here suggest that the ap parent “recovery― from SLD after fractionated dose treat ments with AMO might be due entirely or in part to recovery from PLO.