Cell Proliferation and Cell Loss in Progression in Liver Carcinogenesis: A New Hypothesis
It is becoming well established that the development of hepatocellular carcinoma in the liver of the rat occurs through a number of steps (8 to 10 or more), some of which involve changes in a rare cell and others the progressive modulation of the phenotype in new hepatocyte populations1. Two major sequences appear in the majority of the models of liver carcinogenesis1,2. Sequence A, consisting of initiation and promotion, generates benign focal proliferations of hepatocytes (“clonal nodules”), a very small proportion (1–5%) of which persist2. Sequence B, consisting of progression, is the multistep process whereby the first precancerous lesion, the persistent hepatocyte nodule, slowly undergoes a series of changes leading to cancer. This sequence also includes the changes that occur in a bona fide cancer leading to increasing growth, invasion and metastasis2. Clearly, sequence B is the most relevant and most critical in the development of cancer. It can occur “spontaneously” and needs no external manipulation and is often not influenced in a major way by promoting environments.
KeywordsCell Loss Precancerous Lesion Cyproterone Acetate Orotic Acid Liver Carcinogenesis
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