Evidence for the Hormone Dependency of Hepatic Hyperplastic Nodules: Inhibition of Malignant Transformation After Exogenous 17β‐Estradiol and Tamoxifen

Abstract

Hepatic hyperplastic nodules (HHNs) in rats were studied as an experimental prototype of oral contraceptive‐related hepatic tumors. We have found cytoplasmic estrogen receptors in HHNs produced by acetylaminofluorene (AAF) (four cycles of 0.02% in diet). Rats with AAF‐induced HHNs were randomized into four groups: (i) AAF‐treated control; (ii) estrogen alone (estradiol‐17β); (iii) tamoxifen alone, and (iv) estrogen + tamoxifen. After 8 months of treatment with estrogen (estradiol‐17β) in combination with tamoxifen, there was regression of nodular involvement and no evidence of malignant transformation. Decreased nodular proliferation also occurred after 2 and 4 months treatment with estradiol‐17β and after 8 months of tamoxifen administration. The incidence of hepatocellular carcinoma after 8 months of treatment was significantly less after treatment with estrogen (40%) or tamoxifen (42.9%) when compared to AAF‐treated controls (87.5%). The number of ‐γ‐glutamyitranspeptidase‐positive foci were reduced in all treatment groups after 2,4, and 8 months of treatment; these changes were most pronounced in the estrogen‐treated group and did not directly correlate with the per cent inhibition of malignant transformation. Our results suggest that the malignant transformation of estrogen receptor‐positive HHNs is hormone dependent. Copyright © 1983 American Association for the Study of Liver Diseases