Abstract
A new hypothesis leading to a new model of liver carcinogenesis is described; it is based on the acquisition by carcinogen-altered hepatocytes during initiation of a new functional handle--resistance to the cytotoxicity of a carcinogen--and on the ability of such cells to proliferate in an environment that prevents proliferation of normal hepatocytes. The creation of such a differential environment now enables a quantitative analysis for initiation, the beginning synchronization of the putative premalignant hepatocytes for about 15 cell cycles, the study of the pattern of growth of such resistant cells to form nodules that have some resemblance to the organizational pattern of fetal liver, the analysis of the appearance of distinctive positive and negative markers for these cells, and the further investigation of the development of liver cancer from such cells. The remarkable similarity in overall pattern betweeen the development of cancer in the skin and in the liver with chemicals and the possible role of both somatic mutation and neodifferentiation in carcinogenesis are briefly discussed.
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Selected References
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