MODERATE ENHANCEMENT OF THE PROMOTION PHASE OF SKIN TUMORIGENESIS IN HAIRLESS MICE BY TOPICAL PRETREATMENT WITH A MITOSIS-INHIBITING EPIDERMAL PENTAPEPTIDE

The effect of the physiological epidermal proliferation inhibitory sub stance (EPP) pG1u-G1u-Asp-Ser-G1yOH on the promotion phase in two-stag e carcinogenesis was investigated. EPP could be the active component i n what has been called epidermal chalone. Hairless mice were given an initial application of 100 nmol 7,12-dimethylbenz[a]anthracene in 200 mu l acetone. One week later promotion was started with topical applic ations of 17 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a w eek. Ninety minutes before each TPA application the control group rece ived a topical application of 200 mu l reagent grade acetone and the t wo experimental groups were given either 0.005% or 0.01% EPP in 200 mu l acetone. The mice were observed for time of occurrence and time of regression of papillomas. The number of tumors produced by the group g iven the inhibitory substances before TPA increased, and so did the pe rcentage of tumor-bearing animals. There was also a tendency towards a higher degree of papilloma regression in the animals treated with EPP before TPA. We have previously shown that EPP enhances methylnitrosou rea (MNU) carcinogenesis. Since we regard TPA as a skin-irritating pro moter with weak carcinogenic potency, very different from MNU, the fac t that EPP has the same enhancing effect on promotion as it has on com plete MNU carcinogenesis raises some very interesting questions, and m ay indicate a similarity between the mechanisms in promotion and compl ete carcinogenesis. Some possible explanations of the results are disc ussed, e.g. whether the transit zone late G(1)/S of the cell cycle is the most sensitive one for carcinogenic or tumorigenic effects.