Oral contraceptive steroids as promoters or complete carcinogens for liver in female Sprague-Dawley rats.

Published reports have described an increased incidence of adenomas and of hepatocellular carcinomas in livers of women with a history of long-term oral contraceptive use. Evidence derived from human and experimental animals suggests that oral contraceptive steroids may be liver tumor promoters. Experiments were designed to determine the initiating and/or promoting potential of two oral contraceptive steroids, namely mestranol and norethynodrel. The results show that: mestranol and norethynodrel can promote DEN-initiated hepatocarcinogenesis, as indicated by increased numbers of gamma-glutamyl transpeptidase-positive, putative preneoplastic lesions and by the appearance of carcinomas. Various synthetic estrogens fail to cause detectable levels of DNA damage in hepatocytes. Mestranol has weak, if any, initiating potential. Neither mestranol nor norethynodrel exhibits antiglucocorticoid activity. Mestranol and norethynodrel inhibit metabolic cooperation in V-79 Chinese hamster cells. Taken together, these results and those reported by others demonstrate that oral contraceptive steroids are relatively strong promoters of hepatocarcinogenesis and have little if any genotoxic effect.