Lack of hepatogenotoxicity of oral contraceptive steroids

The objective of the present study was to determine whether mestranol could initiate hepatocarcinogenesis and whether various gonadal steroids have detectable hepatogenotoxic potential. To test for initiation potential, female, Sprague-Dawley rats were partially hepatectomized and intubated with mestranol (100 or 500 mg/kg) 24 h later. Twenty-four hours after treatment all rats were transferred to diet containing 0.05% phenobarbital to promote hepatocytes initiated by mestranol treatment. Four months later an analysis of putative preneoplastic gamma glutamyl transpeptidase positive foci indicated that mestranol did not cause a significant increase in the number of such foci. Hepatogenotoxicity was assessed in two ways, first using alkaline elution to detect liver DNA damage after in vivo treatment with mestranol, and second by detection of DNA repair synthesis in primary cultures of hepatocytes treated with various oral contraceptive steroids. The results of both studies were negative. In conclusion, the oral contraceptive steroids do not exhibit strong initiating or genotoxic potential.