Oncogenic transformation of mouse BALB/3T3 cells by plutonium-238 alpha particles

The A31-11 mouse BALB/3T3 cell system was adapted for the study of malignant transformation induced by 5.3 MeV alpha particles from a specially constructed 238Pu source. The biologic effects were compared to those of 220 kVp X rays. The alpha-radiation survival curve showed a D0 of 70 rad and a relative biological effectiveness (RBE) of 3.5 at 50% survival. The transformation frequency increased exponentially with dose in the range examined (25-250 rad); the maximum RBE for the induction of transformation in growing cells was approximately 3. The RBE for alpha transformation in nonproliferating cells, however, appeared to be much higher; the yield of transformants among X-irradiated cells held in the stationary phase of growth for 6 to 220 hr after irradiation declined nearly 50-fold while no decrease occurred in alpha-irradiated cells. This finding supports the hypothesis that carcinogenic damage induced by high LET radiation in mammalian cells is inefficiently repaired compared with X-ray damage, and that the carcinogenic effect of exposures to high LET radiation may be simply cumulative in nature. It further suggests that the effective RBE for alpha radiation in nonproliferating cell populations in vivo may be much higher than one would predict based on measurements in dividing cells.