Cellular Analysis of Liver Carcinogenesis. III. Comparison of the Ultrastructure of Hyperplastic Liver Nodules and Hepatocellular Carcinomas Induced in Rat Liver by 2-Fluorenylacetamide<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>

Abstract

The ultrastructure of hyperplastic liver nodules and hepato-cellular carcinomas induced in rat liver by 2-fluorenylacetamide (2-FAA) was studied and compared to gain further insight into the biology of the oncogenic process and the possible role of the hyperplastic liver nodule as an intermediary cell population between normal hepatocytes and hepatocellular malignancy. Cells obtained from hepatocellular malignancies typically showed marked variation of their cytostructure. In contrast, a relatively uniform cytological structure characterized hepatocytes within hyperplastic liver nodules. The fine structure of malignant hepatoma cells was not significantly altered when the host animals were fasted for 24 hours before being killed, whereas the hyperplastic liver nodule cells displayed considerable difference in ultrastructure after a fast. A number of similarities were observed between organelles within cells of hyperplastic liver nodules and malignant hepatomas. Both lesions had similar features including prominence of smooth endoplasmic reticulum, often in cluster formation, and a relative paucity of parallel-arrayed, rough endoplasmic reticulum. Annulate lamellae, previously reported present in 2-FAA-induced hyperplastic liver nodules, were also readily detected in malignant hepatomas. Since the above alterations were not observed in liver adjacent to hyperplastic liver nodules, these observations indicate that cells in the hyperplastic liver nodules have certain resemblances to those in liver cancer. However, the hyperplastic liver nodule is composed of cells which differ significantly and reproducibly from those within either normal liver or overtly malignant hepatocellular carcinoma.