LIGHT-MICROSCOPIC AND ELECTRON-MICROSCOPIC AUTORADIOGRAPHIC ANALYSIS OF PROLIFERATING CELLS DURING THE EARLY STAGES OF CHEMICAL HEPATOCARCINOGENESIS IN THE RAT INDUCED BY FEEDING N-2-FLUORENYLACETAMIDE IN A CHOLINE-DEFICIENT DIET

Abstract

Proliferating cells that appear after feeding the hepatocarcinogen N-2-fluorenylacetamide in a choline-deficient diet were identified by autoradiographic electron and light microscopy. Labeled cells are first seen as nondescript periductular cells 1 day after feeding carcinogen. Proliferation of duct lining cells begins at 2-3 days. For the next 3 wk there is proliferation and extension of a mixture of nondescript cells and cells with a duct-like appearance from the portal zone into the adjacent liver. By 3-4 wk the entire liver lobule contains this new cell population. At 3 wk more differentiated duct-like structures are seen at the edge of the advancing new cell population. Newly appearing duct-like cells differ from normal duct cells in that they contain .alpha.-fetoprotein and albumin. The new cell population may arise from duct cells or periportal stem cells, or both.