Experimental induction of hepatocellular carcinoma as a paradigm for carcinogenesis.

The current status of our understanding of the step-by-step development of cancer in the liver in the rat, initiated with chemical carcinogens, is reviewed briefly. The carcinogenic process consists of a sequence of changes in rare hepatocytes, some of which become evident by clonal expansion to form nodules, separated by long periods of progressive change in gene expression. Cell proliferation is important in initiation, in promotion and in progression as well as in cancer per se. Some of the known mechanisms for initiation, promotion and progression are briefly reviewed. The apparent similarity between the process of cancer development in the experimental animal and in the human is emphasized. The possible relation of the process to oncogenes and growth factors is discussed briefly.