TRANSITORY CELL ANTIGENS OF RAT LIVER. III. THE REAPPEARANCE OF α‐FETOPROTEIN DURING CHEMICAL CARCINOGENESIS

When rats were fed a basal diet containing 0.01 to 0.04% 3′‐methyl‐4‐dimethyl‐aminoazobenzene (3′DAB), no serum α‐fetoprotein (αFP) was detected by gel immunodiffusion techniques during the first month of ingestion. On the contrary, with 0.06% 3′DAB in the same basal diet, α‐FP was detected after only two weeks in the sera of almost all animals, irrespective of age at the onset of feeding. An even earlier “reappearance” of α‐FP was observed with the hepatocarcinogen dimethylnitrosamine, given in drinking water. However, the frequency of α‐FP reappearance was dependent on the age of the animals when treatment was begun. Once detected, the α‐FP persisted in the blood for some time and was independent on the continued administration of carcinogen. The reappearance was characterized by several waves of α‐FP secretion over a given period. Animals whose serum α‐FP level became stabilized had a high probability of developing an hepatocellular carcinoma. Nevertheless, in 30% of hepatoma bearing animals, α‐FP could not be detected. Administration of the basal diet either alone or supplemented with 0.06% of the non‐carcinogenic 4′‐methyl‐4‐dimethylamino‐azobenzene also resulted in α‐FP reappearance. However, here the reappearance took place later and at a frequency equal to or lower than 30%. In the light of the above results, the reported specificity of the association between serum α‐FP and primary liver cancer should be reconsidered, at least during the early stages of the neoplastic transformation.