Hyperplasia of Syrian hamster epidermis induced by single but not multiple treatments with 12-O-tetradecanoylphorbol-13-acetate.

Treatment of initiated hamster skin with 12-O-tetradecanoylphorbol-13-acetate does not promote the formation of papillomas and carcinomas as it does in the classic two-stage epidermal carcinogenesis model in many strains of mice. We have begun to examine the basis of this species specificity to TPA. We have found that, although hamster and mouse epidermis respond to a single exposure of TPA with a comparable degree of hyperplasia, they differ in their response to multiple treatments. In contrast to the reported potentiation of hyperplasia of mouse skin following two or more treatments with TPA, hamster skin is capable of adapting to multiple exposures to the promoter. Weekly TPA treatments of hamster skin result in hyperplasia of 4 to 6 nucleated cell layers after the first treatment, reduced hyperplasia after the second treatment, and no hyperplasia after 4 weeks of treatment. Decreasing the time interval between treatments accelerates the adaptation process. This adaptation phenomenon should be useful in studying the mechanism of TPA action by examining TPA effects in adapted and nonadapted tissues from the same species.