Aneuploidy and progression in promoted preneoplastic foci during chemical hepatocarcinogenesis in the rat.

Since a number of rat hepatocarcinomas are aneuploid, the model DNA content of enzyme-altered foci was determined cytospectrophotometrically, to assess if ploidy changes occur before cancer is established. Male F344 rats treated with diethylnitrosamine and promoted with a choline-deficient, phenobarbital supplemented diet showed in most enzyme-altered foci a multimodal ploidy distribution with diploid, tetraploid and octoploid peaks. A minority of foci, however, exhibited an aneuploid pattern. This change in ploidy reflects irreversible genomic alterations, indicative of tumor progression. Thus, promotion and progression may coexist simultaneously in this model of carcinogenesis, long before hepatomas can be diagnosed.