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

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 repa...

Full description

Saved in:
Bibliographic Details
Published in:Carcinogenesis (New York) 1996-05, Vol.17 (5), p.1153-1156
Main Authors: Martelli, Antonietta, Mattioli, Francesca, Ghia, Marco, Mereto, Eugenio, Brambilla, Giovanni
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cells, Cultured
Chlormadinone Acetate - toxicity
Cyproterone Acetate - toxicity
DNA Repair - drug effects
Drug toxicity and drugs side effects treatment
Female
Humans
Liver - drug effects
Liver - metabolism
Male
Medical sciences
Megestrol - analogs & derivatives
Megestrol - toxicity
Megestrol Acetate
Miscellaneous (drug allergy, mutagens, teratogens...)
Pharmacology. Drug treatments
Progesterone Congeners - toxicity
Rats
Rats, Sprague-Dawley
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/17.5.1153