Early HistolÃ3gica!and Functional Alterations of Ethionine Liver Carcinogenesis in Rats Fed a Choline-deficient Diet1

The effects of feeding a choline-deficient (CD) or a choline-supplemented diet upon the early stages of DLethionine carcinogenesis in rat liver were investigated. Low levels of ou-ethionine (0.05 and 0.10%) when fed with a CD diet were found to induce within 4 weeks a massive proliferation of oval cells without significant cell necrosis or presence of inflammatory cell infiltrates. The same levels of ethionine when fed with a choline-supplemented diet caused no significant histolÃ3gica! alteration of the liver. In rats fed the CD plus ethionine diets concomitant with the proliferation of oval cells, there was a marked elevation in the content of «,-fetoprotein in both liver and plasma. After specific immunofluorescence staining, oval cells stained intensely for albumin and <x,-fetoprotein. Hepatocytes stained only for albumin, and bile duct cells stained for neither albumin nor «,-fetoprotein. These re sults indicate that a diet deficient in choline markedly alters the response of rat liver to carcinogenetic doses of ethionine. Thus, ethionine hepatocarcinogenesis in rats fed a CD diet may be a useful model for the exploration of the mechanism(s) whereby a dietary factor influences hepatocarcinogenesis.