Alpha-fetoprotein: cellular origin of a biological marker in rat liver under various experimental conditions.

Alpha1-fetoprotein (AFP) was detected by serological, light and electron microscopic methods in various experimental models. These included (a) liver regeneration after partial hepatectomy or CCl4 intoxication (mouse and rat); (b) liver intoxication by high doses of N-nitrosomorpholine (NNM) and chemical induction of hepatomas (rat). AFP levels varied greatly according to the animal species and strains used. Low and high AFP-producing species and strains were distinguished. In liver regeneration after hepatectomy or CCl4 intoxication, cellular AFP was found in the cytoplasm of hepatocytes. In NNM-intoxicated livers, elevated AFP levels were associated with proliferation of canalicular epithelial cells in which AFP was localized. In early stages of hepatocarcinogenesis, significant AFP increase occurred after high-dose carcinogen feeding and AFP was also localized in proliferating canalicular epithelial cells. On low-dose NNM feeding, no cellular AFP was detected unless hepatomas had developed. At the stage of malignant conversion, distinct AFP staining and non-AFP staining hepatocellular carcinomas appeared in livers.