Development of Preneoplastic and Neoplastic Lesions of the Liver in Male Rats Given 0.025 Percent N-2-Fluorenyldiacetamide2

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Abstract
Three hundred sixty-eight male rats were fed 0.025 percent N-2-fluorenyldiacetamide in a semisynthetic diet for varying periods until there were hyperplastic lesions of the liver. The carcinogenic diet was then discontinued so that the evolution of such lesions could be studied. Cirrhosis developed simultaneously with hyperplasia of the parenchymal cells as long as the carcinogen was fed. After feeding of the carcinogen was discontinued, the cirrhosis decreased in severity and regressed whereas the hyperplastic hepatic cells continued to grow. The change of the parenchymal cells from hyperplastic to neoplastic took place gradually over a long period. Before becoming well-developed carcinomas, areas of hyperplasia passed through the stages of nodules of hyperplasia, nodules with atypical cells, and small hepatocellular carcinomas. Most carcinomas were well differentiated histologically, with the remaining highly or poorly differentiated. Only a few of the earliest hyperplastic lesions progressed to carcinomas. Some of them disappeared. Most underwent degenerative cytoplasmic changes. On the other hand, the nodules of hyperplasia, present when the carcinogen was discontinued, usually developed into hepatocellular carcinomas or remained as nodules. The rate at which the hyperplastic lesions grew depended on the duration of carcinogen administration; the lesions developed most typically after 16 weeks on carcinogenic diet. With shorter or longer periods of feeding, it was more difficult to distinguish histologically between hyperplastic nodules and well-differentiated hepatocellular carcinomas because the cords were so well formed in the carcinomas. The biological behavior of the carcinomas depended on the morphologic pattern, size, and duration of carcinogen feeding.

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