The effect of the tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on UV- and MNNG-induced sister chromatid exchanges in mammalian cells.
The induction of sister chromatid exchanges (SCE) by the tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) has been studied in V79 Chinese hamster cells comparing control untreated cells with either UV-irradiation or MNNG-treated cells. In untreated cells TPA induced SCE at a very low concentration. An increase of approximately 50% over the level of spontaneous SCE formation was observed. In UV-irradiated cells, TPA, when present after the UV-irradiation, significantly enhanced UV-induced SCE formation, more SCE being induced than the expected sum of SCE formed by the separate treatments. TPA also enhanced MNNG-induced SCE but only when it was present for 28 h before, and not after, the MNNG-treatment. The protease inhibitor antipain fully inhibited TPA-induced SCE but did not inhibit UV-induced SCE. When UV-irradiated cells were treated with both TPA and antipain the enhanced UV-induced SCE induction was only partly inhibited by antipain, showing that TPA is responsible for two independent effects, both leading to SCE formation. These results are discussed in relation to the hypothesis that tumour promotion by TPA may depend on the enhancement of mitotic recombination leading to the segregation of a mutational event.
D000818:Animals; D006224:Cricetinae; D003434:Crossing Over, Genetic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000528:radiation effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014466:Ultraviolet Rays
D010704:Phorbols; D008769:Methylnitronitrosoguanidine; D013755:Tetradecanoylphorbol Acetate