DNA Content of Liver Cell Nuclei of N-2-Fluorenylacetamide-Induced Altered Foci and Neoplasms in Rats and Human Hyperplastic Foci2

Abstract

The DNA content of cell nuclei of liver lesions induced in inbred male ACI rats by administration of 0.02% N-2-fluorenylacetamide (2-FAA) diet was measured with a microspectrophotometer in Feulgen-stained specimens. Altered liver foci of the eosinophilic, clear, and simple basophilic (toluidine blue weakly positive or negative) types had modal DNA values with a wider deviation (2C-10C) than the euploid pattern of normal hepatocytes (2C-6C). However, the DNA histograms of cells in hyperbasophilic (intensely toluidine blue-positive) foci were aneuploid (2C-18C) and resembled those of cells in hepatocellular carcinomas (2C-23C). Conversely, the modal DNA values of neoplastic nodules showed a narrower range (2C-12C). These results confirm that the hyperbasophilic foci may be a population similar to carcinoma in situ or may be a direct precursor lesion of hepatocellular carcinoma. In the livers from 4 humans, 3 of whom had a history of long-term use of some drugs, multiple hyperplastic foci resembling eosinophilic or clear cell foci in rats were identified. The modal DNA values of the cell nuclei in these foci showed a wider deviation (2C-10C) than in surrounding hepatocytes (2C-6C). In 2 patients, the lesions contained neoplasms and, therefore, hyperplastic foci in humans may be related to tumor development.