On the Promoting Action of Tamoxifen in the P-Dimethylaminoazobenzene Induced Hepatocarcinogenesis CF1 Mice Model and the Cytoprotective Role of Heme Oxygenase

Carcinogenesis is a multistage, multimechanism process, involving the irreversible alteration of an initiated cell, followed by its clonal proliferation, from which the acquisition of the invasive and metastatic phenotypes are generated (Trosko and Chang, 2001). Chemically induced and spontaneous liver tumors share some metabolic alterations. We have developed an experimental mice model, by administrating p-dimethylaminoazobenzene (DAB) in the diet, to study the onset of hepatocarcino-genesis, that includes a primary activating liver stage, provoking biochemical alterations that lead to the true initiation step (Gerez et al., 1997; Vazquez et al., 1999). Tamoxifen (TMX) has proven to be an effective palliative treatment for advanced breast cancer with low reported incidence of side effects (Forbes, 1997). It has been observed, that TMX is a carcinogen capable of both initiating and promoting liver carcinogenesis in female rats (Dragan et al., 1996). Recently, we have demonstrated that TMX produced changes in hepatic enzyme activities which may be relevant to the metabolism and disposition of this and/or other drugs. We have found that long-term treatment with TMX enhances hepatocarcinogenesis induced by DAB (Caballero et al., 2001).