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A Morphological and Histochemical Study of Carcinogenesis of the Liver in Rats Fed 3'-Methyl-4-dimethylaminoazobenzene¹

Department of Pathology, University of Wisconsin School of Medicine, Madison, Wisconsin 53706

Histological and histochemical studies of livers from rats sacrificed at intervals after they were fed 3'-methyl-4-dimethylaminoazobenzene for 46 days suggest that there are two different pathways of progression from preneoplastic lesions to hepatic carcinomas.

In one sequence, hepatocytes that were deficient in glucose 6-phosphatase and formed prominent hyperplastic nodules appeared to develop into hepatocellular carcinomas that were also deficient in this enzyme. The carcinomas were moderately well differentiated and first appeared 9 weeks after drug discontinuation. Two types of cells that were deficient in glucose 6-phosphatase were seen in the hyperplastic nodules: large hydropic-appearing cells containing glycogen that frequently showed degenerative changes and less frequent, variably sized basophilic cells that were more similar to induced hepatocellular carcinomas, since both were deficient in glycogen.

In a second sequence, foci of cells within areas of cholangiofibrosis appeared to give rise to cholangiocarcinomas that also contained areas of poorly differentiated hepatocellular carcinomas. These pleomorphic carcinomas were more than three times as frequent as the homogeneous hepatocellular carcinomas and were first seen 4 weeks after drug discontinuation. Progression from cholangiofibrosis to the pleomorphic cholangiocarcinomas was suggested by the finding of transition from the hyperplastic to the malignant lesions and by high levels of butyrocholinesterase in both. The enzyme similarities seem especially significant in view of the absence of butyrocholinesterase in biliary ducts and ductules and its only mild activity in persisting hepatocellular nodules.

¹ The research reported in this paper was supported by USPHS Grant CA-08202. Presented in part at the 58th Annual Meeting of the American Association for Cancer Research in Chicago, Ill., April 15, 1967.

Received 12/29/72. Accepted 1/29/73.