Promotin action of tamoxifen in a model of hepatocarcinogenesis induced by p-dimethylaminoazobenzene

CABALLERO, F.; GEREZ, E.; OLIVERI, L.; FALCOFF, N.; BATLLE, A.; VAZQUEZ, E.

Birmingham - UK

Congreso; 18 th International Congress of Biochemistry and Molecular Biology - Beyond the Genome; 2000

Tamoxifen (TMX) has proven to be an effective palliative treatment for advanced breast cancer with low reported incidence of acute side effects. Nevertheless, TMX was demonstrated to be hepatocarcinogenic in rats when administered daily in the diet. It is also a promoting agent in the multistage model of hepatocarcinogenesis in rat. To document the long term effect of TMX in the liver of mice treated with p-dimethylaminoazobenzene (DAB), we investigated the time response of these drugs on different biochemical parameters. Male CF1 mice were employed . Animals received DAB (0,5% w/w) and / or TMX (0,025% w/w) in the diet during a whole period of 28 weeks. Control animals were fed with a standard laboratory diet for the same period. The ratio of liver weight to body weight was significantly increased in DAB and DAB+TMX groups. Glutathione S transferase, a key enzyme of hepatic metabolism, increased in all treated groups, reflecting liver damage. The high TBARS levels and the alteration of the activities of the antioxidant enzymes, catalase and superoxide dismutase, demonstrated the oxidative state provoked by these drugs. Histological studies revealed liver cell hyperplasia in the groups DAB and DAB+TXM; however, only in the group that received the co-treatment solid, trabecular and acinar hepatocellular carcinoma was confirmed at the end of the experimental trial. These results demonstrated that TMX supports tumor promotion in mice liver initiated with DAB. Because the natural history of the hepatic neoplastic disease rodents and humans is similar, the possible hazard of the long term therapy with TMX might be considered.