Enhancement of rat hepatocellular-altered foci by the liver tumor promoter phenobarbital: evidence that foci are precursors of neoplasms and that the promoter acts on carcinogen-induced lesions.

Altered foci resistant to iron accumulation were induced by N-2-fluorenylacetamide in livers made siderotic by feeding 8-hydroxyquinoline and ferrous gluconate to inbred F344 rats. Following cessation of carcinogen feeding, most foci reverted to iron accumulation and could no longer be detected by 24 weeks, but some persisted for this interval. Futhermore, in 2 groups, 33 and 50% of rats developed liver tumors by 24 weeks after removal of the carcinogen. The addition of phenobarbital to the diet after cessation of carcinogen feeding enhanced persistence of altered foci and increased the incidence of liver tumors to 78--89%.