Inhibitory effects of uterine endometrial carcinogenesis in Donryu rats bytamoxifen

The effects of tamoxifen (TAM) on uterine carcinogenesis were investigated in female Donryu rats; The effects were initiated by a single intrauterine treatment with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at a dose of 20 m g/kg body weight via the vagina at 10 weeks of age. TAM tubes (cholesterol tubes containing 50% TAM) were implanted into the backs of the rats for 13 months (full TAM group) or for the second-half of this period (half TAM gro up). In the control group treated with ENNG alone, various proliferative le sions were induced in the uterine endometrium and the incidence of endometr ial adenocarcinomas was about 30%. In contrast, the uteri in both TAM-treat ed groups showed severe atrophy and the incidences of uterine proliferative lesions were limited to a few endometrial hyperplasias in the half TAM gro up. Most of the vaginas in both TAM-treated groups showed mucification, whi le cornification was common in the vaginal epithelium of controls. The ovar ies demonstrated similar atrophy with cystic follicles and no corpora lutea in all groups. Other estrogen responsive endocrine organs, such as the pit uitaries and adrenals, were small in the TAM-treated groups. Serum estrogen levels in the TAM-treated groups were lower than in the control group but progesterone levels did not differ. These results indicated that TAM acts a s an anti-estrogen on the adult rat uterus, inhibiting the development of e ndometrial adenocarcinomas initiated by ENNG. (C) 1998 Elsevier Science Ire land Ltd. All rights reserved.