PMID: 7542174Jul 1, 1995Paper

DNA-damaging activity of the cyproterone acetate analogues chlormadinone acetate and megestrol acetate in rat liver

Carcinogenesis
J TopinkaT Wolff

Abstract

The synthetic progestin cyproterone acetate (CPA) has been recently shown to elicit DNA repair synthesis in cultured rat hepatocytes and to form adducts with rat hepatocyte DNA in vitro and in vivo. In the present study we have examined the genotoxic potential of the structural analogues of CPA, chlormadinone acetate (CMA) and megestrol acetate (MGA) in rat liver cells. CPA strongly induced DNA repair synthesis in hepatocyte cultures from females but not from males. In contrast, CMA and MGA (2-50 microM) did not detectably increase repair synthesis in cultured hepatocytes from either gender. CMA and MGA, however, caused the formation of DNA adducts detectable by the 32P-postlabelling technique. At a concentration of 30 microM, between 30 and 50 adducts/10(9) nucleotides were found with MGA and CMA in cultured hepatocytes of female rats, and between 5 and 20 adducts/10(9) nucleotides were found in hepatocytes of males. By comparison, 30 microM CPA has been found to produce 1670 adducts/10(9) nucleotides in hepatocytes from female rats. CMA and MGA also induced low levels of DNA adducts in vivo. When female rats were treated with 100 mg/kg of CMA or MGA per os, the adduct levels were 2 and 19 adducts/10(9) nucleotides respectivel...Continue Reading

Citations

Aug 1, 1998·Toxicology in Vitro : an International Journal Published in Association with BIBRA·W FeserW Kuhnz
Dec 5, 2002·Mutation Research·Giovanni Brambilla, Antonietta Martelli
Nov 17, 2001·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·A G Abdel-RahmanM A Mustafa
May 10, 2005·Environmental and Molecular Mutagenesis·Theo M de KokJos C Kleinjans
Feb 12, 2002·Environmental Health Perspectives·Frederica P PereraVirginia A Rauh
Feb 26, 1998·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·E Pucci, F Petraglia
Oct 11, 2008·Mutation Research·Giovanni Brambilla, Antonietta Martelli
Jun 5, 2004·Toxicology Letters·H F P JoostenE I Krajnc
Dec 8, 2004·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Yasir Hasan Siddique, Mohammad Afzal
May 20, 2005·Human & Experimental Toxicology·Yasir Hasan SiddiqueMohammad Afzal
May 11, 2018·Drug and Chemical Toxicology·Eyyüp Rencüzoğulları, Muhsin Aydın

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