Journal Article

Promotion, but not progression, effects of tamoxifen on uterine carcinogenesis in mice initiated with <i>N</i>-ethyl-<i>N′</i>-nitro-<i>N</i>-nitrosoguanidine

Masakazu Takahashi, Takasumi Shimomoto, Katsuhiro Miyajima, Seiichi Iizuka, Takao Watanabe, Midori Yoshida, Yuji Kurokawa and Akihiko Maekawa

in Carcinogenesis

Volume 23, issue 9, pages 1549-1555
Published in print September 2002 | ISSN: 0143-3334
Published online September 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.9.1549
Promotion, but not progression, effects of tamoxifen on uterine carcinogenesis in mice initiated with N-ethyl-N′-nitro-N-nitrosoguanidine

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Effects of tamoxifen (TAM) on development of uterine endometrial carcinogenesis were studied in intact and ovariectomized (OVX) mice initiated with N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG). In experiment I, animals were implanted with cholesterol (ChL, controls) or TAM (5% w/w) and/or 17β-oestradiol (E2, 0.5% w/w) pellets s.c. from 9 to 25 weeks of age, until the termination of the experiment, and all received a single intra-uterine administration of ENNG (12.5 mg/kg) at 10 weeks of age. They were divided into four groups: ENNG + ChL (control), ENNG + TAM, ENNG + E2 and ENNG + TAM + E2. Endometrial proliferative lesions (hyperplasias and/or carcinomas) were observed in all groups, the incidences in the TAM- and/or E2-treated groups being two times higher than in the ChL-treated control animals. High induction (11/20, 55%) of adenocarcinomas was observed in the E2 group but this was significantly decreased in combination with TAM (2/20, 10%), no carcinomas being found in the TAM group. In experiment II, animals pre-treated with TAM (10 weeks) and receiving E2 post-treated (4 weeks) developed adenocarcinomas, although no cancers were observed in mice treated by ChL instead of TAM. In animals pre-treated with TAM and post-treated with ChL or TAM, no adenocarcinomas were also developed. In OVX mice (experiment III), proliferative lesions were observed in the TAM- and/or E2-treated groups, at incidences significantly higher than in ChL-treated animals, in which these lesions were completely absent. However, no adenocarcinomas were found, only slight hyperplasias being observed in the TAM group, although the incidence of adenocarcinoma was highest in the E2 alone group, and significantly decreased in combination with TAM, as in experiment I. These results indicate that TAM may itself exert promotion effects, while exhibiting an anti-progression influence on uterine carcinogenesis in adult mice initiated by ENNG and receiving E2.

Keywords: ChL, cholesterol; ENNG, N-ethyl-N′-nitro-N-nitrosoguanidine; E2, 17β-oestradiol; P, progesterone; E2: P ratio, 17β-oestradiol: progesterone ratio; TAM, tamoxifen.

Journal Article.  5419 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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