Cyproterone acetate induces DNA damage in cultured rat hepatocytes and preferentially stimulates DNA synthesis in γ-glutamyltranspeptidase-positive cells

摘要: The synthetic anti-androgen and progestin cyproterone acetate (CPA) is known to increase the liver tumor rate in rats. tumorigenicity of CPA has been attributed a tumor-promoting activity steroid. In order discover whether acts directly on preneoplastic cells or via indirect effects, we investigated stimulates replicative DNA synthesis vitro hepatocytes isolated from carcinogen-treated rats (two-thirds hepatectomy, 1 x 30 mg diethylnitrosamine per kg 0.1% phenobarbital drinking water) degree stimulation differs gamma-glutamyltranspeptidase (GGT)-positive, putatively GGT-negative, 'normal' hepatocytes. possibility that might also have initiating potential was by studying its effects repair synthesis. Stimulation [3H]thymidine incorporation into only observed presence epidermal growth factor (EGF) (10 ng/ml) insulin mU/ml). Maximal were obtained between 2 10 microM. EGF/insulin reduced 'pure' flutamide, but stimulated promegestone. CPA, EGF insulin, labelling index twice as high GGT-positive GGT-negative cells, regardless mitogens added at 48 72 h. did not differ negative when omitted. These findings are consistent with idea activity. significantly induced both untreated This detected concentration low microM maximal 20 results indicate tumor-promoting, genotoxic chemical, i.e. it an potential.