Preneoplastic Livers Cells Isolated by Centrifugal Elutriation from Normal and Isozyme Profiles of Oval Cells, Parenchymal Cells, and Biliary

The fetal liver ¡sozymes aldolase A and pyruvate kinase K increase in livers of adult rats fed a choline deficient-diet contain ing 0.1% ethionine. Oval cells isolated by centrifugal elutriation from preneoplastic livers of animals receiving the carcinogenic diet contained these fetal forms as well as fetal-adult isozyme hybrids. In contrast, parenchymal cells isolated from the livers of these animals had only aldolase B and pyruvate kinase L, the same isozymes present in parenchymal cells of normal adult rats. Liver homogenates from rats receiving the carcinogenic diet contain lactate dehydrogenase (LDH) 1, LDH 2, and LDH 3 in addition to LDH 4 and LDH 5, which are the forms detected in normal liver homogenates. LDH 1, LDH 2, and LDH 3 are present in oval cells of preneoplastic livers and in biliary epithelial cells of normal livers, but not in parenchymal cells isolated from normal and preneoplastic livers. Cells of biliary epithelium from normal livers also contain aldolase A and pyruvate kinase K, but not the fetal-adult isozymes present in oval cell populations. The results indicate that, in animals receiving this carcinogenic diet, isozyme alterations associated with neoplasia result from the proliferation of a new cell population which contains these en zymes and not from "dedifferentiation" of mature hepatocytes. Furthermore, the data suggest that this new cell population may include a liver stem cell compartment containing cells in transi tional states of differentiation.