Enhancement of carcinogen-induced mutations or recombinations by 12-O-tetradecanoyl-phorbol-13-acetate in the mammalian spot test

The mammalian spot test is suitable for detecting gene mutations and reciprocal recombinations. When given alone 12-O-tetradecanoyl-phorbol-13-acetate (TPA) did not have any statistically significant effect upon these genetic alterations. In combination with ethylnitrosourea (ENU) however TPA enhanced the effect of the mutagen/carcinogen. The effective dose range of TPA + ENU was very small, i.e., between 2 X 0.2 and 2 X 0.33 mg/kg, but the effect was very strong as shown by the steep slope of the dose-effect curve. The results agree with the hypothesis that the mode of action of cocarcinogens and tumor promoters is a genetic one and that recombination plays an important role in this process.