ABSTRACT
Hepatic carcinomas were induced with the administration of diethyl-nitrosamine (DEN) in rats. The morphological changes of the liver tissues in the course of carcinogenesis could be divided into 3 successive stages: the nonspecific changes reacting to the drug toxicity, non-cancerous hyperplastic nodules of hepatocytes and ductular cystadenomatous lesions,and the lesions of genuine malignancy including hepatocellular carcinoma and cholangiocarcinoma.The ultrastructural alterations of hepatocellular carcinoma showed a complicate picture and were related to the differentiation of the tumor cells. In one case of cholangiocarcinoma, numerous cytoplasmic dense-core granules similar to the neurosecretary granules seen in apudoma were found in some of the tumor cells, which is postulated to be a special type of cholangiocarcinoma. On the basis of the results, Ihe histogenesis of the neoplasms after DEN administration is considered to originate from hyperplastic nodules of hepatic cells and ductular hyperplasia.