Promoting action of tamoxifen in a model of hepatocarcinogenesis induced by p-dimethyl-aminoazobenzene.

CABALLERO, FABIANA; GEREZ, ESTHER; OLIVERI, LEDA; FALCOFF NORA; BATLLE, ALCIRA; VAZQUEZ, ELBA

Birmingham, UK

Congreso; 18TH. INTERNATIONAL CONGRESS OF BIOCHEMISTRY AND MOLECULAR BIOLOGY; 2000

International Union of Biochemistry and Molecular Biology (IUBMB), Biochemical Society, FEBS

Tamoxifen (TMX)  has proven to be an effective palliative treatment for advanced breast cancer with low reported incidence of acute side effect. Nevertheless, TMX was demostrated to be hepotocarcinogenic in rats when administrated 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 iver 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 whole period of 28 weeks. Control animals were fed with a standart laboratory diet for the same period. The ratio of liver weight to body weigth was significantly increased in DAB and DAB+TMX groups. Glutathione S transferase, a key enzyme of hepatic metabolism, increased in all treated groups, relecting liver damage. The high TBARS levels and the alterations of  the activities of the antioxidant enzymes, catalase ans superoxide dismutase, demostrated the oxidative state provoked by these drugs. Histological studies revealed liver cell hyperplasia in the groups DAB and DAB+TMX; however, only in the group that received the cotreatment solid, trabecular and acinar hepatocellular carcinoma was confirmed at the end of the experimental trial. These results demonstrated that TMX supports tumor promotion in the mice liver iniciated with DAB. Because the natural history of the hepatic neoplastic disease in rodents and humans is similar, the possible hazard of the long term therapy with TMX might be considered.