Liver Tumor Promotion and Breast Cancer Chemoprevention: Common Mechanisms

Carcinogenesis has been operationally divided into three stages (Fig. 1) (Dragan and Pitot 1992). The first stage is initiation, which involves an irreversible genetic change that occurs in cells either spontaneously or upon exposure to chemical and physical agents. The reversible process of promotion, the second stage of neoplastic development, selectively expands the number of these initiated cells. The final stage of tumor development is progression. It entails the accumulation of additional genetic lesions that result in the activation of oncogenes and/or the inactivation of tumor suppressor genes (Vogelstein and Kinzler 1993). It is during this latter stage of tumor development that hepatocellular carcinomas are observed forming within benign adenomas.