Promotion, dose rate, and repair processes in radiation-induced neoplastic transformation

C3H10T1/2 cells were exposed to low doses of 60Co gamma rays at 100 or 0.10 cGy/min and the incidence of neoplastic transformation was assayed with or without the addition of tetradecanoylphorbol-13-acetate (TPA). As we reported earlier [A. Han, C. K. Hill, and M. M. Elkind, Cancer Res. 40, 3328-3332 (1980); C. K. Hill, A. Han, F. Buonaguro, and M. M. Elkind, Carcinogenesis 5, 193-197 (1984)], the frequency of neoplastic transformation per unit dose following low doses appears to be linear and is reduced 2.3-fold at 0.10 cGy/min compared to 100 cGy/min. We report now that the addition of TPA 24 h after irradiation appreciably enhances the frequency after both low- and high-dose-rate exposures. The enhancement indicates that TPA leads to the expression of potentially effective, preneoplastic damage due to gamma rays. Our data suggest that the enhancement of transformation by TPA is essentially independent of dose rate. Also, our results suggest that the sector of preneoplastic damage which is repaired during protracted exposures becomes unavailable to enhancement by TPA.