Dose Dependent Induction of DNA Adducts, Gene Mutations, and Cell Proliferation by the Antiandrogenic Drug Cyproterone Acetate in Rat Liver
Formation of DNA adducts is regarded as the initial event in the multistep process of chemical carcinogenesis. The primary DNA damage can become permanent when the cells carrying the primary DNA damage divide and gene mutations arise. A wide variety of bacterial and mammalian in vitro systems have been developed to test for mutations and a plethora of chemicals have been already identified as mutagens in these systems. However, the in vitro tests have limitations. For example, the metabolic systems employed to activate promutagens may be not appropriate to activate every test compound. Moreover, in vitro systems are not suitable to study all factors affecting the mutagenicity of a compound in vivo, such as pharmakokinetics of the genotoxicant, cell proliferation and apoptosis. Therefore, in vivo studies are required to obtain realistic data on the mutagenicty of chemical agents which may improve the scientific basis for risk estimation.
KeywordsAgar Adduct Half Life Lime Progesterone
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- Lang, R., and Reimann, R., 1993, Studies for a genotoxic potential of some exogenous and endogenous sex steroids. 1. Communication: Examination for the induction of gene mutations using Ames Salmonella/microsome test and the HGPRT test in V79 cells, Environm. Mol. Mutagenesis 21:272–304.CrossRefGoogle Scholar
- Martelli, A., Brambilla-Campart G., Allavena, A., Mereto, E., Brambilla, G., 1996,Induction of micronuclei and initiation of enzyme-altered foci in the liver of female rats treated with cyproterone acetate, chlormadinone acetate, or megestrol acetate, Carcinogenesis 17:551–554.PubMedCrossRefGoogle Scholar
- Schulte-Hermann, R., Tinunermann-Trosiener, I., and Schuppler, J., Promotion of spontaneous preneoplastic cells in rat liver as a possible explanation of tumor production by nonmutagenic compounds, Cancer Res. 43: 839–844.Google Scholar
- Topinka, J., Binkova, B., Schwarz, L.R., and Wolff T., 1996, Cyproterone acetate is an integral part of hepatic DNA adducts induced by this steroidal drug,17:167–169.Google Scholar