Promoter-enhanced neoplastic transformation after gamma-ray exposure at 10 cGy/day

We have measured gamma-ray-induced neoplastic transformation in C3H10T1/2 mouse embryo cells irradiated at an average 10 cGy/day throughout the useful life span of these cells for transformation studies. At cumulative total doses of 50, 150, 300, and 450 cGy, samples of cells were assayed for cell survival and neoplastic transformation with or without the administration of 0.1 micrograms/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA) starting 24 h after the irradiation. The results indicate that, at a dose rate of 10 cGy/day, the rate of induction of neoplastic transformation is reduced by a factor of thirteen compared to that at 100 cGy/min. Still, frequencies above the background level are observed. These results are consistent with previous data which, at 144 cGy/day (0.1 cGy/min), showed that radiation-induced initiation events could be repaired during exposure, thus reducing the frequency of transformation from that observed at 100 cGy/min [A. Han et al., Cancer Res. 40, 3328-3332 (1980)]. Although the addition of TPA after the delivery of a particular dose at 10 cGy/day produced a significant increase in the frequency of neoplastic transformation, the degree of enhancement was less than after higher-dose-rate exposures [C.K. Hill et al., Radiat. Res. 109, 347-351 (1987)]. These results indicate that during 7 weeks of exposure, the repair of radiation-induced initiation was extensive but not complete, and suggest that a significant part of the damage persists which can be promoted by TPA. These observations support the inference that initiation and promotion are not tightly coupled and are probably independent processes.