Serum α-fetoprotein (AFP) concentrations were determined by a sensitive radioimmunoassay throughout various carcinogenic regimens at several concentrations of N-2-acetylaminofluorene (AAF) and diethylnitrosamine (DEN). A number of results derived from these experiments demonstrated striking differences between the effects of these hepatocarcinogens. The almost immediate elevation of AFP resulting from exposure to AAF at all levels tested was absent with DEN; AFP elevation occurred only after a significant number of weeks of DEN exposure. This and other findings suggest that neither hepatocyte injury alone nor selected hepatocyte gene derepression, as related to carcinogenicity, is responsible for the early AFP elevation with AAF and other carcinogens. We postulate, rather, that AAF stimulates the production of AFP by a specific cell population, as has been suggested in the literature, which may or may not be related to carcinogenesis.
The rise of AFP, when it did occur after DEN exposure, was rapid and progressive and appeared to be associated with the presence of histologically malignant cell foci. DEN exposure resulted in a much earlier appearance of hepatocellular carcinomas than with AAF. These were almost invariably multiple and associated with microscopic foci of malignancy, neither finding being demonstrated with AAF. The DEN-induced carcinomas invariably produced AFP while many which resulted from AAF exposure did not. Therefore, since every rat exposed to a carcinogenic regimen of AAF demonstrated a remarkably similar kinetic of AFP response, the pattern for a given rat was not predictive of the functional activity of the carcinomas which resulted.
These experiments were supported by Grant CA-20657 and Contract VO-1-CP-33403 awarded by the National Cancer Institute, Department of Health, Education, and Welfare.