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Heterogeneity of alpha-fetoprotein(AFP) and albumin containing cells in normal and pathological permissive states for AFP production: AFP containing cells induced in adult rats recapitulate the appearance of AFP containing hepatocytes in fetal rats.

The cellular localization of alpha-fetoprotein (AFP) and albumin (ALB) in permissive states for AFP synthesis has been examined. The cells containing AFP associated with permissive states in the adult are similar in appearance to cells that are present during the development of fetal liver. In fetal liver, AFP is seen in most developing hepatocytes ranging from small 'oval' like cells to larger dividing hepatocytes and in cells organized in glandular structures. Following exposure to some chemical hepatocarcinogens, AFP can also be seen in small 'oval' cells, ductal-like cells, and larger atypical hepatocytes that form glandular-like structures. Following partial hepatectomy or galactosamine-induced live injury, AFP is seen in a few large parenchymal cells usually containing identifiable chromatin Cells which contain AFP almost always contain ALB as well, but for each cell type there are many more ALB containing cells than AFP containing cells. ALB and AFP containing hepatoma cells are more frequently located adjacent to tumor vessels and AFP production by hepatoma 777 in vitro is associated with the growth state of the tumor. The AFP containing cells that are seen during restitutive proliferation most likely arise from deregulation of proliferating adult hepatocytes. The non-hepatoma AFP containing cells that appear early during carcinogenesis may arise in the adult by retrodifferentiation of hepatocytes or by proliferation of stem cells. These morphologically different AFP containing cells may or may not be precursors of the hepatocellular carcinomas which develop later.