[Evolution of hepatocyte population in the process of chemical carcinogenesis]

Abstract

By means of two different markers of differentiation, using immunofluorescene method, the authors have characterized changes in the population of hepatic cells 1-8 weeks following the start of 3'-methyl-4-dimethyl-aminoazobenzene or 2-acetyl-aminofluorene action. Alpha-fetoprotein served as a marker of embryonic hepatocyte differentiation; while ligandin-as a marker of high-differentiated mature hepatocytes. The toxic effect of the carcinogens on hepatic stem cells was accompanied with a decrease of ligandin content in centrilobular hepatocytes. Among newly proliferating elements "oval" cells, cells of bile tract epithelium and most of basophilic hepatocyte-like cells fail to contain either alpha-fetoprotein or ligandin. Small groups of basophilic hepatocyte-like cells would contein alpha-fetoprotein. In cells of high cylinder-shaped epithelium of intestinal type ligandin was found, but alpha-fetoprotein was not found. The latter was absent in oxyphilous hepatocytes of hyperplastic nodules. In terms of ligandin content three types of morphologically identical nodules were differentiated; a) ones not containing this protein, b) ones containing it in amounts common to normal mature hepatocyte, and c) hyperdifferentiated nodules containing abnormally high concentrations of ligandin. Within one nodule cell all cells were identical in ligandin content. Thus, it is shown that at early stages of chemical carcinogenesis there occure in the liver multiple foci of differentiation of various kind. These intensive processes are assumed to be essential for tumor evolution in the tissue.