Influence of 3-methylcholanthrene on liver carcinogenesis in rats ingesting DL-ethionine, 3'-methyl-4-dimethylaminoazobenzene, and N-2-fluorenylacetamide.
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Biomedical subjects
Publications and source records attributed to E Farber.
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Within 3.5 to 4 hours after thionine administration, numerous small osmiophilic bodies, liposomes, appear in the endoplasmic reticulum of the liver cells. By fusion, the liposomes lead to the formation of larger collections of fat, giant liposomes. Adenine administration to ethionine-treated rats removes the liposomes from the hepatocytes and causes the transitory appearance of osmiophilic droplets in the sinusoidal space of Disse. The characteristic disaggregation of hepatic polysomes seen in the liver after ethionine administration is corrected by the injection of adenine.
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The effect of portal diversion by ameroid constriction was studied in the carcinogenic process in the rat after initiation of foci by diethylnitrosamine and after the establishment of putative preneoplastic nodules. Portal diversion or portal diversion plus partial hepatectomy did not act to promote or select for the development of nodules. Furthermore, portal diversion did not alter the natural history of established nodules. These results suggest that vascular factors are not important at these early stages of the carcinogenic process in the rat liver.
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.
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