Journal Article

Comparative study of DNA repair induced by cyproterone acetate, chlormadinone acetate and megestrol acetate in primary cultures of human and rat hepatocytes

Antonietta Martelli, Francesca Mattioli, Marco Ghia, Eugenio Mereto and Giovanni Brambilla

in Carcinogenesis

Volume 17, issue 5, pages 1153-1156
Published in print May 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.5.1153
Comparative study of DNA repair induced by cyproterone acetate, chlormadinone acetate and megestrol acetate in primary cultures of human and rat hepatocytes

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Cyproterone acetate (CPA), a synthetic progestin recently found to induce genotoxic effects in hepatocytes from female rats and from humans of both genders, and two structural analogues, chlormadinone acetate (CMA) and megestrol acetate (MGA), have been compared for their capacity to induce DNA repair synthesis as measured by quantitative autoradiography. Exposure of primary human hepatocytes for 20 h to concentrations of CPA, CMA and MGA ranging from 2 to 50 uM induced positive responses in cultures from donors of both genders and the amounts of DNA repair elicited by the three progestins were similar. Under the same experimental conditions substantial differences were observed in the amounts of DNA repair elicited by the three progestins in primary hepatocytes from female rats, their potency decreasing in the following order CP≫ CM≫ MGA, and the three compounds failed to induce DNA repair in hepatocytes from male rats. These results, which agree with previous findings, suggest that for these sex steroids extrapolation to humans of results obtained in rats might be questionable.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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