Radiation-induced neoplastic transformation of stationary phase C3H/10T1/2 cells in response to different dose rates and to post-irradiation treatment with tumor promoter

Abstract

The induction of neoplastic transformation by exposure to high (HDR, 0.66 Gy/min) or very low (LDR, 4.8 × 10 −4 Gy/min) dose rates of 137Cs gamma-rays was studied in C3H/10T1/2 mouse embryo fibroblasts. Cells in stationary phase were exposed in the dose range 1–6 Gy in combination with a post-irradiation treatment with the tumor promoter, 12- O-tetradecanoylphorbol-13-acetate (TPA). The post-irradiation treatment with TPA during 6 weeks of transformation assay did not induce any notable increase in the slope of the dose-response curves for transformation frequency, compared to the conditions without TPA treatment. The lack of an enhancing TPA effect at both dose rates applied in this study may be related to the fact that the cells were irradiated in the stationary growth phase. Thus, the results differ from those generally obtained when exponentially growing cells are exposed to gamma-rays and afterwards treated with TPA in the transformation assay. Earlier studies of exponentially growing C3H/10T1/2 cells exposed to different dose rates show a significantly higher transformation frequency for high dose rate. This study, using stationary phase cells, also shows that the slopes of dose response curves for transformed foci were somewhat higher (about 1.5-fold) for HDR exposure compared with LDR exposure. However, the difference was not statistically significant.