Oval cells--hepatocytes relationships in Dipin-induced hepatocarcinogenesis in mice

During Dipin-induced hepatocarcinogenesis in mice there is powerful and prolonged proliferation of oval cells which are arranged in duct-like structures. Ultrastructure and differentiation pathways of oval cells depend on their location in the liver lobule. The major part of oval cells is represented by duct lining cells morphologically similar to biliary epithelial cells. They form the system of branching anastomozing ducts and expand into the parenchyma from portal to central veins. Later these ducts disintegrate. In the periportal areas, three stages of oval cell differentiation can be distinguished: (1) low differentiated cell similar to cells of terminal biliary ductules in their size and ultrastructure, (2) transitional cells and (3) young hepatocytes. Cells with ultrastructural characteristics of sequential stages of hepatocyte differentiation are located within the ducts surrounded by the basal lamina. Our data suggest that oval cells are the committed cell precursors capable of differentiating into hepatocytes or biliary epithelial cells in the periportal microenvironment.