EFFECT OF PHORBOL MYRISTATE ACETATE ON RECOVERY OF SPONTANEOUS AND ULTRAVIOLET LIGHT-INDUCED 6-THIOGUANINE AND OUABAIN-RESISTANT CHINESE-HAMSTER CELLS

Abstract

12-O-Tetradecanoyl-phorbol-13-acetate (TPA) and phorbol were tested in Chinese hamster [V79 lung] cells for their effects on mutagenesis (resistance to 6-thioguanine and ouabain), DNA repair and survival after UV irradiation. Recovery of 6-thioguanine- and ouabain-resistant colonies was increased by TPA treatment and, to a lesser extent, by phorbol in UV-irradiated cells. Maximum enhancement of recoverable UV-induced 6-thioguanine- and ouabain-resistant mutants occurred when TPA was present after the mutation expression time and after the completion of DNA repair. This enhancement effect, while persisting up to 18 days in the 6-thioguanine mutation system, was maximal when TPA was applied about 2 days after UV irradiation for the ouabain resistance mutation system. No significant decrease in cell survival was noted after post-UV treatment with TPA or phorbol, under conditions where there was a slight but nonspecific inhibition of unscheduled DNA repair synthesis. These results do not support the hypothesis that the tumor-promoting activity of TPA is due to its ability to inhibit error-free excision repair. The results are consistent with a 2-stage hypothesis of carcinogenesis which includes mutational and epigenetic mechanisms to explain the initiation and promotion phases.