Experimental studies on hepatocarcinogenesis induced by oral contraceptives, with special reference to estrogen receptor and the effect of tamoxifen.
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Hepatocarcinogenesis induced by ethynylestradiol (E.E.) was investigated especially on estrogen receptor and the effect of antiestrogen agent, tamoxifen (TAM). Female rats of Wistar strain aged 4 weeks were used. In E.E. group, rats were daily given 0.075 mg of E.E. dissolved in 0.5 ml olive oil through a gastric tube for one year. In the other three groups, 0.075 mg of E.E. and 0.5 mg of TAM in 0.5ml of olive oil (E.E.+TAM group), 0.5 mg of TAM in 0.5 ml olive oil (TAM group) and 0.5 ml of olive oil alone (control group) were administrated daily, respectively, for one year the same method in E.E. group. The liver weight and DNA contents in the liver cell nuclei increased markedly in E.E. group, as compared with those in the other three groups. In E.E. group, hyperplastic nodules were observed in all rats at 4-months after start of drug administration and hepatocellular carcinoma developed in 5.9% of rats at the end of this experiment for 12 months. On the contrary, neither tumors nor hyperplastic nodules developed in the other groups. Estrogen receptor in cytosol of the liver tissue was positive in the groups of E.E. and control, while it was negative in the groups of E.E.+TAM and TAM. As a results, the administration of TAM completely inhibited hepatocarcinogenesis induced by E.E. It is, therefore, suggested that E.E. has a direct effect on hepatocarcinogenesis, combining with estrogen receptor of the liver cell.
- 社団法人 日本肝臓学会の論文