Quantitative relationship between hepatocytic neoplasms and islands of cellular alteration during hepatocarcinogenesis in the male F344 rat.

Hepatocytic neoplasms (nodules and carcinomas) and islands of cellular alteration which display abnormal retention of glycogen on fasting were quantified in F344 male rats at intervals after initiation of hepatocarcinogenesis by the combination of a two-thirds partial hepatectomy with a single treatment with methyl(acetoxymethyl)-nitrosamine during the subsequent peak of DNA synthesis in regenerating livers. In initiated rats fed the liver tumor promoter phenobarbital, yields of neoplasms and islands maintained a constant numerical relationship over time, with one neoplasm emerging for every 1600 islands. Significantly fewer neoplasms developed in rats not fed the phenobarbital, although the numbers of islands observed at 45 and 60 weeks after initiation were not significantly increased by the promoter. The ratio of islands to neoplasms in rats not fed the phenobarbital was about 11,000:1. Dietary phenobarbital appeared to have an effect on initiated hepatocytes (or latent neoplasms) that was not revealed by its effects on the growth and size of the island population.