Martelli A, Mattioli F, Ghia M, Mereto E, Brambilla G
Institute of Pharmacology, University of Genoa, Italy.
Carcinogenesis. 1996 May;17(5):1153-6. doi: 10.1093/carcin/17.5.1153.
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 microM 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 CPA > CMA > 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.
醋酸环丙孕酮（CPA）是一种合成孕激素，最近发现它能在雌性大鼠和男女两性人类的肝细胞中诱导遗传毒性效应。通过定量放射自显影测定，已对其与两种结构类似物醋酸氯地孕酮（CMA）和醋酸甲地孕酮（MGA）诱导DNA修复合成的能力进行了比较。将原代人肝细胞暴露于浓度范围为2至50微摩尔的CPA、CMA和MGA中20小时，在男女两性供体的培养物中均诱导出阳性反应，并且这三种孕激素引发的DNA修复量相似。在相同实验条件下，观察到雌性大鼠原代肝细胞中这三种孕激素引发的DNA修复量存在显著差异，其效力按以下顺序递减：CPA > CMA > MGA，并且这三种化合物在雄性大鼠肝细胞中未能诱导DNA修复。这些结果与先前的发现一致，表明对于这些性类固醇，将在大鼠中获得的结果外推至人类可能存在疑问。
