An electron microscope study of hepatocellular changes in the rat during chronic treatment with acetamide....

Male Leeds strain rats were fed a diet containing 5.0% by weight of acetamide (AA), for up to 35 weeks, inducing a high incidence of hepatic cell neoplasms. The sequential morphological changes induced by AA in the hepatic parenchymal cells were studied by electron microscopy and were compared with those observed in foci of cellular alteration, neoplastic nodules and hepatocellular carcinomata. The observed fine structural changes including early glycogen depletion, dispersal and dislocation of the rough endoplasmic reticulum (ER), smooth ER proliferation and nuclear irregularity and nucleolar abnormalities. Glycogenosis developed in some cells during treatment and was characteristic of the 'clear cell' foci, as well as being common in the neoplasms. The most consistent alteration, observed in parenchymal cells and the cells of foci, nodules and carcinomas, was that involving the rough ER. This persisted after withdrawal of AA from the diet, whereas many other changes were transient, and may represent a change in differentiation associated with neoplastic induction.