Localization of alpha-1-fetoprotein and DNA-synthesis

Six-, 12and 20-week-old rats were fed N-nitrosomorpholine (NNM) at low concentrations (6 mg/kg/day) or high concentrations (20 mg/kg/day) for 6 or 12 weeks. Irrespective of the age of the rats, both NNM schedules resulted in development of hepatomas and during the early stages of hepatoma induction, liver histotoxic patterns depended only on the dose of carcinogen employed. Necrosis of hepatocytes and proliferation of small, oval-shaped cells occurred when high doses of NNM were applied. Parallel to the proliferation of oval-shaped cells, resurgence of alpha-1-fetoprotein (AFP) in rat sera was observed and production of this protein was confined to the oval-shaped cells as shown by immunoperoxidase staining.