bol were tested in Chinese hamster cells for their effects on mutagenesis (resistance to 6-thioguanine and to ouabain), DNA repair, and survival after ultraviolet (UV) irradiation. Recovery of 6-thioguanine- and ouabain-resistant colonies

12-O-Tetnadecanoyl-phonbol-13-acetate (TPA) and phon bol were tested in Chinese hamster cells for their effects on mutagenesis (resistance to 6-thioguanine and to ouabain), DNA repair, and survival after ultraviolet (UV) irradiation. Recovery of 6-thioguanineand ouabain-resistant colonies was significantly increased by TPA treatment and, to a lessen extent, by phonbol in UV-innadiated cells. Moreover, maximum enhancement of recoverable UV-induced 6-thio guanineand ouabain-resistant mutants occurred when TPA was present after the mutation “expression― time and after the completion of DNA repair. This enhancement ef fect, 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 muta tion system. No significant decrease in cell survival was noted after post-UV treatment with TPA on phonbol, under conditions where there was a slight but nonspecific inhibi tion of unscheduled DNA repair synthesis. These results do not support the hypothesis that the tumor-promoting activ ity of TPA is due to its ability to inhibit “error-free― excision repair. The results are, however, consistent with a “two stage― hypothesis of carcinogenesis which includes muta tional and epigenetic mechanisms to explain the initiation and promotion phases.