Further evidence that the survival of irradiated mammalian cells is controlled by temporal processes.

Theories of mammalian cellular radiosensitivity that exclude metabolic modification of radiation damage are untenable (Nagasawa et al., 1980). Evidence supporting that conclusion has been obtained from experiments with a radiosensitive, proliferating cell, the S/S variant of the L5178Y murine leukaemic lymphoblast, and a radioresistant, nondividing cell, the retinal photoreceptor (rod) of the rabbit. When S/S cells (mid-) G1 + 8 h in the cycle, at the peak of radioresistance, were X-irradiated at 37 degrees C and then treated hyperthermically (12 h, 38.7-40.3 degrees C), the survival curve, which has a shoulder at 37 degrees C, changed progressively to the simple exponential obtained for G1 cells. Under conditions where Ne ions (LET = 35 keV microns-1) have a relative biological effectiveness (RBE) of approximately 2 for normally radioresistant cells in vitro and in situ, the RBE for G1 S/S cells was approximately 1. Neon ions (1-50 Gy) caused similar amounts of DNA damage in S/S cells and photoreceptors, but the cellular responses were very different. After 5 Gy, the surviving fraction of asynchronous S/S cells was 10(-5), DNA structures were not restored and by 8 h post-irradiation extensive DNA degradation was evident; in the retina, however, the photoreceptor complement was unchanged for greater than 1 year, DNA structures appeared to be restored and remained so (many months) until late DNA degradation began. These phenomena can be explained satisfactorily only if temporal processes play a significant role in cellular radiosensitivity.