Rapid development of large numbers of alpha-fetoprotein-containing "oval" cells in the liver of rats fed N-2-fluorenylacetamide in a choline-devoid diet
Sell, S.; Leffert, H.L.; Shinozuka, H.; Lombardi, B.; Gochman, N.
Gan 72(4): 479-487
1981
ISSN/ISBN: 0016-450X PMID: 6171471 Document Number: 172185
Fischer rats, fed 0.05% w/w N-2-fluorenylacetamide in a choline-devoid diet for 2 weeks, develop a massive infiltration of the liver by small "oval" cells. This occurs rapidly one week after feeding the diet for two weeks. All rats fed choline-devoid diet die within 5 weeks, with massive oval cell infiltration of the liver. Although similar changes occur in rats fed N-2 fluorenylacetamide in a choline-supplemented diet, their degree is much less. In rats fed a choline-devoid diet without N-2-fluorenylacetamide, proliferation of hepatocytes, but not of oval cells, is observed. Because the carcinogen-enhancing effects of choline-devoid diets seem to exceed those of partial hepatectomy, such diets may work by causing changes distinct from those induced by partial hepatectomy. Many oval cells contain alpha-fetoprotein, and the rapid oval cell increase is associated with an exponential increase in serum alpha-fetoprotein concentration. These observations suggest that a cellular change, not an alteration of gene expression in parenchymal cells, is the primary cause of hyper-alphafetoproteinemia during the course of chemical carcinogenesis in rats.