Evidence for the hormone dependency of hepatic hyperplastic nodules: inhibition of malignant transformation after exogenous 17 beta-estradiol and tamoxifen.
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-17 beta); (iii) tamoxifen alone, and (iv) estrogen + tamoxifen. After 8 months of treatment with estrogen (estradiol-17 beta) 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-17 beta 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 gamma-glutamyltranspeptidase-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.
D015073:2-Acetylaminofluorene; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004958:Estradiol / Q000627:therapeutic use*; D006965:Hyperplasia; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000032:analysis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009376:Neoplasms, Hormone-Dependent; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*
D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D013629:Tamoxifen; D004958:Estradiol; D015073:2-Acetylaminofluorene