Busulfan胎生期曝露による第一次卵胞減少はDonryuラットの子宮発癌を促進する
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概要
- 論文の詳細を見る
Ovarian dysfunction leading to hormonal imbalance plays a crucial role in uterine carcinogenesis in rats as well as women. However, the effects of a reduction in primordial follicles at birth on uterine adenocarcinoma development have hitherto not been determined. The present study was therefore conducted using female Donryu rats, a high incidence rat strain of uterine adenocarcinoma. The animals were maternally exposed to 2.5 or 5.0 mg/kg of busulfan on gestation day 14 to reduce primordial follicles, and were then initiated by intrauterine treatment with N-ethyl-N-nitro-N- nitrosoguanidine at 11 weeks of age. Both busulfan treatment doses caused earlier occurrence of persistent estrus, with dose-dependence as compared to controls. At 15 months of age, the rats were euthanized. The incidence of uterine adenocarcinomas and multiplicity of uterine neoplastic lesions were significantly increased by the 5.0 mg/kg, but not the 2.5 mg/kg busulfan treatment. Morphologically, the ovaries exposed to busulfan treatment exhibited severe atrophy, with few or no follicles and corpus lutea. Serum 17β-estradiol (E2), progesterone, and inhibin levels were significantly decreased in the busulfan treatment groups, with a clear dose-relation. Interestingly, only the 5.0 mg/kg busulfan treatment elevated the E2/progesterone ratio. These results provide evidence that the reduction of primordial follicles promotes uterine adenocarcinoma development in rats in association with an earlier occurrence of the persistent estrus status.
- 日本繁殖生物学会の論文
著者
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WATANABE Gen
Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Toky
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TAYA Kazuyoshi
Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Toky
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Shirota Mariko
Hatano Research Institute, Food and Drug Safety Center
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渡辺 元
食品薬品安全センター秦野研究所
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吉田 緑
(財)佐々木研究所 病理部
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吉田 緑
佐々木研究所 病理部
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Taya Kazuyoshi
Laboratory Of Veterinary Physiology Department Of Veterinary Medicine Faculty Of Agriculture Tokyo U
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Shirota Mariko
Hatano Res. Inst. Food And Drug Safety Center
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代田 真理子
Hatano Research Institute Food And Drug Safety Center
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MAEKAWA AKIHIKO
Department of Pathology, Sasaki Institute
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YOSHIDA Midori
Department of Pathology, Sasaki Institute
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Yoshida Midori
Department Of Pathology Sasaki Institute
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Watanabe Gen
Laboratory Of Veterinary Physiology Department Of Veterinary Medicine Faculty Of Agriculture Tokyo U
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渡辺 元
Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Toky
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吉田 緑
Department of Pathology, Sasaki Institute
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Maekawa Akihiko
Department Of Pathology Nagoya City University Medical School
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Watanabe Gen
Laboratories Of Veterinary Physiology Dep. Of Veterinary Medicine Fac. Of Agriculture Tokyo Univ. Of
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SHIROTA Mariko
Hatano Research Institute of Food and Drug Safety Centre
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