ALTERED UTERINE SENSITIVITY TO OXYTOCIN AND PROSTAGLANDIN-F2-ALPHA INDIMETHYLBENZ(A)ANTHRACENE (DMBA)-INDUCED RAT MAMMARY-CARCINOMA - THE EFFECTS OF TAMOXIFEN AND OR RECOMBINANT HUMAN INTERFERON-ALPHA-2B THERAPY/

This study aimed to investigate the long-term toxicity of a preventive regimen of tamoxifen (TAM) and recombinant human interferon alpha 2b (rHuIFN alpha 2b) on the uterine responsiveness of tumour-bearing rats . The experimental tumour was induced by dimethylbenz(a)anthracene (DM BA) in virgin female albino rats and the therapy was started two month s after carcinogen administration. The acute effect of DMBA on the ute rine sensitivity was also assessed 24 h post-carcinogen. The uterotoni c potentials of oxytocin and prostaglandin F-2 alpha (PGF(2) alpha) we re markedly reduced in the control tumour-bearing group as compared to the normal one. Similarly, acute DMBA administration showed reduced u terine sensitivity to both agents. Treatment with either TAM or combin ed TAM/rHuIFN alpha 2b did not affect the uterine response to either o xytocin or PGF(2) alpha, while rHuIFN alpha 2b increased the uterine s ensitivity to oxytocin but not to PGF(2) alpha. These data indicate th at the carcinogenic agent per se and the presence of tumour reduce the contractile response in the rat uterus to oxytocic agents. Moreover, combined TAM/rHuIFN alpha 2b does not markedly affect the uterine sens itivity in DMBA-induced mammary carcinoma-bearing rats. (C) 1996 The I talian Pharmacological Society.