Effects of inhibitors of tumor promotion on 12-O-tetradecanoylphorbol-13-acetate-induced keratin modification in mouse epidermis

Abstract

In order to investigate the role that hyperplasia plays in the induction of the keratin modifications by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), the effects of several inhibitors of tumor promotion and cycloheximide on the TPA-induced protein changes were studied. The antiinflammatory steroid fluocinolone acetonide and cycloheximide, which prevent the induction of hyperplasia, were found to prevent the appearance of the TPA-induced keratin modifications. Retinoic acid and tosylphenylalanylchloromethyl ketone, which have minor influence on hyperplasia, were found to have essentially no effect on these protein changes. These results provided further evidence that the TPA-induced epidermal keratin changes were associated with the induction of hyperplasia by TPA and not necessarily related to promoting ability.