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

ABSTRACT-Altered foci resistant to Iron accumulation were Induced by N-2-fluorenylacetamlde In livers made siderotic by feeding 8-hydroxyqulnollne and ferrous gluconate to Inbred F344 rats. Following cessation of carcinogen feeding, most foci re-verted to Iron accumulation and could no longer be detected by 24 weeks, but some persisted for this Interval. Furthermore, 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 per-sistence of altered foci and Increased the Incidence of liver tumors to 78-89%.-J Natl Cancer Inst 61: 1311-1314, 1978. The promoting process in neoplastic development whereby cells exposed to a carcinogen are made to develop into tumors by agents incapable of inducing tumors when acting i~dependently was delineated ex