Chemical carcinogenesis: hepatocyte nodules with a special phenotype as a common step at the crossroads

Unlike the great heterogeneity and diversity in the initial interactions of a chemical carcinogen with DNA and in the phenotypes of the late malignant neoplasms, the intermediate steps in liver carcinogenesis, the hepatocyte nodules, are remarkably similar. This commonality is seen in six different models of liver cancer development using carcinogens and promoters of quite different chemical structure and properties. The hepatocytes in the nodules show a similar arrangement and architecture, cytology and cytochemistry, blood supply, biological behavior, and biochemical pattern. These observations, coupled with the program nature of the remodeling of the hepatocyte nodules, strongly suggest that at least some of the earlier steps in carcinogenesis are of a physiological adaptive nature.