Early Stages of Nodular Transformation of the B6C3F1 Mouse Liver Induced by Choline Deficiency

Abstract

The B6C3F1 strain of mice is prone to develop liver nodules as animals grow older. This spontaneous tumor development is enhanced by dietary lipotrope deficiency. The present studies were performed to evaluate the liver of the B6C3F1 mice in early periods of lipotrope deficiency and before the nodules appear. Mice were fed high levels of dietary fat (cotton seed oil or beef fat) without choline or vitamin B12. The livers of these mice were compared with those of mice subjected to partial hepatectomy or dietary phenobarbital both of which enhance liver nodule formation. The ability of putative preneoplastic hepatocytes to exclude parenteral-administered iron was used to detect this eventual phenotype. A lipotrope-deficient condition was established which typically exhibited fatty liver and increased cell proliferation, the latter measured by autoradiography. In the time periods evaluated the lipotrope-devoid diets were not sufficient to induce nodular or putative preneoplastic lesions. An excessively high activity of p-nitroanisole-O-demethylase and a single small fatty nodule were obtained when phenobarbital was added to the lipotrope-deficient diet. Scattered eosinophilic hepatocytes were seen in every experimental group when the histologic slides were stained for iron pigments, but their biologic significance in the present experiments could not be established. Under the conditions of this study, the liver of the B6C3F1 strain of mouse exhibited only minor indications of future tumor development.