Effects of the antiandrogen, cyproterone acetate, on the induction of papillomas, DNA synthesis and ornithine decarboxylase activity in mouse skin.
The antiandrogen, cyproterone acetate (CPA), applied simultaneously with 12-O-tetradecanoylphorbol-13-acetate (TPA) to the dorsal skin of male and female SENCAR mice initiated with 7,12-dimethylbenz[a]anthracene inhibited the production of papillomas of the skin. Although 125 and 250 micrograms of CPA had no effect on the incidence of papillomas per mouse, 500 micrograms of CPA inhibited papilloma production by 95% and 91% in female mice after 20 and 37 weeks of promotion, respectively. Testosterone propionate only partially blocked the inhibitory effect of CPA. In male mice 500 micrograms and 1 mg of CPA inhibited papilloma production by 77% and 88%, respectively. In the two-stage promotion protocol 500 micrograms of CPA was ineffective as an inhibitor when it was applied with TPA during the 1st stage but inhibited papilloma production by 71% when it was applied with mezerein during the 2nd stage. CPA was also observed to inhibit TPA-stimulated epidermal DNA synthesis and inflammation but had no effect on TPA-induced epidermal ornithine decarboxylase activity.
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens; D003534:Cyproterone / Q000031:analogs & derivatives* / Q000633:toxicity; D017373:Cyproterone Acetate; D004261:DNA Replication / Q000187:drug effects*; D004790:Enzyme Induction; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010212:Papilloma / Q000139:chemically induced* / Q000473:pathology; D012867:Skin / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology; D013997:Time Factors
D000726:Androgen Antagonists; D002273:Carcinogens; D017373:Cyproterone Acetate; D003534:Cyproterone; D009955:Ornithine Decarboxylase