Dr. Mishkin is the recipient of a Chercheur Boursier Award from the Quebec Medical Council (FRSQ).
Article first published online: 21 SEP 2007
Copyright © 1983 American Association for the Study of Liver Diseases
Volume 3, Issue 3, pages 308–316, 1983
How to Cite
Mishkin, S. Y., Farber, E., Ho, R. K., Mulay, S. and Mishkin, S. (1983), Evidence for the Hormone Dependency of Hepatic Hyperplastic Nodules: Inhibition of Malignant Transformation After Exogenous 17β-Estradiol and Tamoxifen. Hepatology, 3: 308–316. doi: 10.1002/hep.1840030306
This work was also presented in part at the Annual Meeting of the Canadian Society for Clinical Investigation (CSCI), September, 1981, Toronto, Ontario, Canada (Clin. Invest Med. 1981; 4:14B) and at the Annual Meeting of the American Association for Cancer Research, St. Louis, Missouri, April, 1982 (Proc. Am. Assoc. Cancer Res. 1982; 23:192).
This work is dedicated to the memory of Moe Yalovsky
- Issue published online: 21 SEP 2007
- Article first published online: 21 SEP 2007
- Manuscript Accepted: 20 DEC 1982
- Manuscript Received: 20 JUL 1982
- Medical Research Council of Canada
- Cedars Cancer Fund of the Royal Victoria Hospital
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.