Enhancing effect of tumor promoter 12-O-tetradecanoylphorbol-13-acetate on 8-azaguanine-resistant mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine in cultured chinese hamster cells.

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Abstract
Effects of a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), on mutagenesis (resistance to 8-azaguanine and to ouabain) in Chinese hamster V79-H3 cells were examined. TPA, at concentrations ranging from 10-6 .mu.g/ml-5 .mu.g/ml, enhanced the frequency of 8-azaguanine-resistant mutation induced by N-methyl-N''-nitro-N-nitrosoguanidine (MNNG). Whether TPA was present during the mutation expression time (0-72 h after MNNG treatment) or during the mutation selection time (72-240 h after MNNG treatment), this enhancing effect was observed. The enhancing effect of TPA reached a plateau at a concentration of 10-5 .mu.g/ml. The effect of TPA possibly was due to its inhibitory action on metabolic cooperation. This possibility was almost eliminated by measuring the amount of actual metabolic cooperation. It is difficult to explain at the molecular level why TPA enhances the frequency of 8-azaguanine-resistant mutation induced by MNNG. The results are consistent with the 2 stage theory of carcinogenesis. TPA did not affect the frequency of ouabain-resistant mutation induced by MNNG.