Transformation-sensitive cells in G2/M-phase are not promoted by TPA following 137Cs gamma-rays

Mouse C3H 10T1/2 cells are most sensitive to radiation-induced neoplastic transformation in the G2/M-phase of the cell cycle. When synchronized 10T1/2 cells were exposed to phorbol 12-myristate 13-acetate (TPA) after irradiation, transformation of cells not in the transformation-sensitive window was enhanced, but transformation of cells already in the transformation-sensitive window was not. Earlier work showed that (a) TPA enhances the frequency of transformation of both high and low dose-rate gamma-irradiated cells by about the same factor, but that (b) TPA enhances the transformation of cells exposed to low dose-rate fission spectrum neutrons appreciably less than cells exposed to high dose-rate fission spectrum neutrons. The latter observation is consistent with the inability of TPA to promote cells in the transformation-sensitive window and with the role of such cells in enhancing transformation by protracted doses of neutrons. The data provide a cellular basis for studying the biochemical/molecular aspects of TPA promotion in vitro.