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Inhibitory effects of uterine endometrial carcinogenesis in Donryu rats by tamoxifen
M Yoshida1, K Kudoh, S Katsuda
1Department of Pathology, Sasaki Institute, Tokyo, Japan. amaekawa@sasaki.or.jp
Abstract:
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 mg/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 group). In the control group treated with ENNG alone, various proliferative lesions were induced in the uterine endometrium and the incidence of endometrial adenocarcinomas was about 30%. In contrast, the uteri in both TAM-treated groups showed severe atrophy and the incidences of uterine proliferative lesions were limited to a few endometrial hyperplasias in the half TAM group. Most of the vaginas in both TAM-treated groups showed mucification, while cornification was common in the vaginal epithelium of controls. The ovaries demonstrated similar atrophy with cystic follicles and no corpora lutea in all groups. Other estrogen responsive endocrine organs, such as the pituitaries 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 as an anti-estrogen on the adult rat uterus, inhibiting the development of endometrial adenocarcinomas initiated by ENNG.
Insights
Tamoxifen (TAM) inhibited uterine cancer development in rats initiated by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). TAM treatment led to uterine atrophy and reduced cancer incidence, demonstrating its anti-estrogenic effects on the uterus.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Uterine carcinogenesis is a complex process influenced by hormonal factors.
- Tamoxifen (TAM) is a selective estrogen receptor modulator with known effects on reproductive tissues.
- Investigating TAM's impact on chemically induced uterine cancer provides insight into its anti-estrogenic mechanisms.
Purpose of the Study:
- To evaluate the effects of tamoxifen (TAM) on the development of uterine adenocarcinomas initiated by N-ethyl-N itro-N-nitrosoguanidine (ENNG) in rats.
- To determine if TAM exhibits anti-estrogenic properties in the adult rat uterus in the context of carcinogenesis.
- To assess the impact of TAM on other estrogen-responsive organs.
Main Methods:
- Female Donryu rats were treated with ENNG to initiate uterine carcinogenesis.
- Tamoxifen (TAM) was administered via implanted cholesterol tubes for varying durations (full or half period).
- Uterine lesions, vaginal epithelium, ovaries, and endocrine organs were histologically examined; serum hormone levels were measured.
Main Results:
- ENNG alone induced significant endometrial adenocarcinoma in control rats (approx. 30% incidence).
- TAM treatment resulted in severe uterine atrophy and significantly reduced proliferative lesions and cancer incidence.
- TAM-treated rats showed vaginal mucification, ovarian atrophy, and smaller pituitary and adrenal glands, with lower serum estrogen levels.
Conclusions:
- Tamoxifen (TAM) acts as an anti-estrogen on the adult rat uterus.
- TAM effectively inhibits the development of endometrial adenocarcinomas initiated by ENNG.
- TAM's anti-estrogenic effects extend to other reproductive and endocrine organs in rats.