Loss of S-phase-dependent radioresistance in irs-1 cells exposed to X-rays.

We measured radiosensitivity throughout the cell cycle in parental V79 cells and a radiation-sensitive mutant isolated from them, irs-1 (Jones et al. (1987) Mutation Res., 183, 279-286). We observed, as expected, large fluctuations in radiosensitivity throughout the cell cycle in parental V79 cells exposed to 5 or 9 Gy X-rays; cells irradiated at the G1/S border were generally radiosensitive whereas cells irradiated in mid- or late-S phase were radioresistant. In sharp contrast to this result, irs-1 cells showed a relatively flat response of radiosensitivity throughout the cell cycle mainly due to a lack of radioresistance during S. In general, irs-1 cells were maximally radiosensitive in phases of the cell cycle where V79 cells were radioresistant, and equally radiosensitive to V79 cells when compared at mitosis, the most radiosensitive phase of the V79 cell cycle. The results suggest that the subset of radiation-induced lesions whose repair is compromised by the irs-1 mutation is similar to the subset of lesions whose repair or expression causes the fluctuations in radiosensitivity throughout the cell cycle in repair-proficient cells. These observations add another unique phenotypic characteristic to the irs-1 mutation.