Inhibitory effects of uterine endometrial carcinogenesis in Donryu rats by tamoxifen

Yoshida, Midori; Kudoh, Kayoko; Katsuda, Shin-ichi; Takahashi, Masakazu; Ando, Jin; Maekawa, Akihiko

doi:10.1016/s0304-3835(98)00240-7

Cited by 13 publications

(6 citation statements)

References 27 publications

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“…This pattern was slightly more pronounced in the Premarin + Acolbifene group and remained preponderant in all groups treated with Acolbifene, including when the SERM was combined with DHEA. Vaginal epithelium mucification has been reported in immature [38] and adult [39] rats under antiestrogen treatment. Although this morphological pattern has been compared to the progesterone-induced mucification [38], the molecular mechanism by which an antiestrogen induces epithelial mucification remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Effects of dehydroepiandrosterone, Premarin and Acolbifene on histomorphology and sex steroid receptors in the rat vagina

Berger

El‐Alfy

Martel

et al. 2005

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Discussionmentioning

confidence: 99%

Effects of dehydroepiandrosterone, Premarin and Acolbifene on histomorphology and sex steroid receptors in the rat vagina

Berger

El‐Alfy

Martel

et al. 2005

The Journal of Steroid Biochemistry and Molecular Biology

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“…Also the incidences of uterine and cervical/ vaginal cancers increased in rats, in the absence of any estrogen agonistic effect, when tamoxifen was administered orally on days 2-5 after birth 54 . Previously we reported that TAM showed potent anti-estrogenic effects on the adult rat uterus and inhibited the development of endometrial adenocarcinomas in our two-stage uterine carcinogenesis model 55 . In that study, however, the dose levels used might have been high.…”

Section: Effects On Uterine Carcinogenesismentioning

confidence: 66%

Toxicologic/carcinogenic Effects of Endocrine Disrupting Chemicals on the Female Genital Organs of Rodents

et al. 2004

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Toxicologic/carcinogenic effects of some representative endocrine disrupting chemicals (EDCs) having estrogenic activity, such as alkylphenols, on the female genital organs of rodents, especially rats, are reviewed and discussed, focusing on our recent research. Neonatal treatment of high-dose p-tert octylphenol (t-OP, 100 mg/kg s.c. injection every other day from postnatal day 1 (PND 1) to PND 15) induced various long-term persistent irreversible effects on the female reproductive system of Donryu rats, such as lower gonadotropin levels at prepuberty, inhibition of uterine gland genesis, persistent estrus and polycystic ovaries. The result indicates that neonatal high-dose treatment of estrogenic EDCs can affect gonadotropin secretion during the developmental period of sexual maturation with direct masculinization of the hypothalamic function. Exposure limited to the first 5 days after birth (PNDs 1-5) to 100 mg/ kg t-OP, however, caused delayed influence which was characterized by accerelated appearance of atrophic ovary, manifested by early-occurring and long-term continuing persistent estrus after puberty, whereas no abnormalities could be found with regard to growth and differentiation of the reproductive organs and the hypothalamo-pituitary-gonadal control system up to maturation, the influence being caused by delayed modulation of the hypothalamo-pituitary-gonadal control system. The most notable effect on the female reproductive system when normal cycling rats were exposed to high-doses t-OP for 28 days, was disappearance of the estrous cycle, but no clear changes were detected in other parameters such as uterine weight and morphology. These results indicate that the most serious issue with EDCs is the potential effects of prenatal and/or neonatal exposure on rodents. Well or moderately differentiated adenocarcinomas increased in Donryu rats initiated with N-ethyl-N'-nitro-N-nitrosoguanidine, when high-dose t-OP was given subcutaneously during adulthood. Neonatal exposure for PNDs 1-5 to high-dose t-OP also showed promoting effects on uterine adenocarcinoma development. However, in rats given t-OP for PNDs 1-15, uterine tumor malignancy was clearly increased, although there was no significant alteration in the total incidence of adenocarcinomas. The results are very interesting in consideration of the histogenesis of uterine adenocarcinomas. However, maternal exposure to low doses of EDCs such as nonylphenol and bisphenol A at actual human exposure levels by the oral route showed no effects on growth and development of the female reproductive system or uterine carcinogenesis. These results indicate that dietary exposure to low doses of EDCs might not induce any adverse effects on the female genital system in mammals including humans. (J Toxicol Pathol 2004; 17: 69-83)

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“…The other chemoprevention study was performed on N-ethyl-N′-nitro-Nnitrosoguanidine-treated Donryu rats. Tamoxifen treatment significantly reduced the number of proliferative lesions in the uteri which also was limited to a few hyperplastic lesions (Yoshida et al 1998). The authors claimed that tamoxifen acted as an antiestrogen, because of decreased serum estradiol levels.…”

Section: Donryu Ratsmentioning

confidence: 99%

Endometrial cancer: experimental models useful for studies on molecular aspects of endometrial cancer and carcinogenesis.

Vollmer

2003

Endocrine-Related Cancer

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There is definitely a need for the development of new drugs for the treatment and cure of endometrial cancer. In addition there are various new drugs or phyto-remedies under development which are intended for use in the treatment and prevention of breast cancer, for the treatment of menopausal symptoms and for hormone replacement therapy. The efficacy of novel drugs targeting steroid receptors in endometrial cancers has to be evaluated and the safety of other endocrine measures on endometrial cancers or on endometrial carcinogenesis has to be assessed. For these experimental purposes five main classes of experimental models are available: spontaneous endometrial tumorigenesis models in inbred animals (Donryu rats, DA/Han rats, BDII/Han rats), inoculation tumors from chunks of tumors (rat EnDA-tumor, human EnCa 101 tumor) or from inoculated tumor cell lines (rat RUCA-I cells, human Ishikawa and ECC-1 cells), developmental estrogenic exposure or chemical carcinogen exposure of CD-1 and ICR mice, transgenic approaches such as mice heterozygous regarding the tumor suppressor gene PTEN (pten + / − -mice) and endometrial tumor cell lines cultured under conditions promoting in vivo-like morphology and functions e.g. cell culture on reconstituted basement membrane. Although the number of models is comparatively small, most aspects related to functions of estrogenic or gestagenic substances are assessable, particularly if various experimental models are combined. Whereas models based on human endometrial adenocarcinoma cells are widely used, the properties and advantages of animal-derived models have mainly been ignored so far.

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Inhibitory effects of uterine endometrial carcinogenesis in Donryu rats by tamoxifen

Cited by 13 publications

References 27 publications

Effects of dehydroepiandrosterone, Premarin and Acolbifene on histomorphology and sex steroid receptors in the rat vagina

Effects of dehydroepiandrosterone, Premarin and Acolbifene on histomorphology and sex steroid receptors in the rat vagina

Toxicologic/carcinogenic Effects of Endocrine Disrupting Chemicals on the Female Genital Organs of Rodents

Endometrial cancer: experimental models useful for studies on molecular aspects of endometrial cancer and carcinogenesis.

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