Correlations between ploidy and initiation probability determined by DNA cytophotometry in individual altered hepatic foci

Abstract

Single cell DNA cytophotometry of ATPase-deficient putative preneoplastic foci in rat liver, induced by a single dose of N-methyl-N-nitrosourea (25 mg/kg or 50 mg/kg) and subsequent phenobarbital feeding (0.05% in the diet), revealed three different types: the majority of foci consisted of an almost exclusive diploid cell population, others showed a preferential tetraploid pattern and a few large foci contained a mixture of di-, tetra- and octoploid hepatocytes. The results of this selective measurement of individual preneoplastic foci in Feulgen-stained 20-microns-thick cryostat sections indicate that not only diploid hepatocytes are a target for the transforming action of a carcinogen, but also tetraploid cells, and that both initiated cell types are capable of expanding as a homogeneous clone. However, clonal homogeneity appears to be lost when foci enlarge. A few preneoplastic foci, heterogeneous with respect to DNA content and endowed with an increased proliferative potential, may represent cell populations at high risk of further development into malignancy.