Comparison of Oval Cells Induced in Rat Liver by Feeding N-2-Fluorenylacetamide in a Choline-devoid Diet and Bile Duct Cells Induced by Feeding 4,4′-Diaminodiphenylmethane¹ Free

Oval cells and duct-like structures produced in the livers of rats fed N-2-fluorenylacetamide in a choline-devoid diet differ from bile ducts produced after feeding 4,4′-diaminodiphenylmethane. Rapid elevations of serum α-fetoprotein (AFP) occur after feeding N-2-fluorenylacetamide in a choline-devoid diet; no elevations of AFP are seen during 4,4′-diaminodiphenylmethane feeding. The duct-like structures associated with oval cells frequently contain AFP and albumin and are faintly delineated by laminin, whereas normal bile ducts and ducts induced by 4,4′-diaminodiphenylmethane do not contain AFP or albumin and are delineated by an intensely staining layer of laminin. Zones of oval cell proliferation label intensely for fibronectin, whereas zones of bile duct proliferation label much less intensely. It is concluded that the “tubuloform degeneration” seen after carcinogen exposure does not necessarily represent differentiation to true bile duct structures and that oval cells may neither derive from nor differentiate into bile ducts. Oval cells have characteristics more like fetal hepatocytes than ductular cells and may represent a “stem cell”-like population with potential for loss of growth control and malignant transformation.