Effects of Endocrine Disrupters (Environmental Hormone) on Sex-Hormone Target Organs and Mammary Carcinogenesis

内分泌干​​扰物（环境激素）对性激素靶器官和乳腺癌发生的影响

• 批准号: 12836013
• 负责人: YOSHIDA Hiroki
• 金额: $ 2.18万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12836013/
• 关键词: Endocrine disruntor; Rat; 7.12-dimethvbenz)a)anthracene; Mammarycarcinoma; 7, 12-dimethylbenz(a)anthracene

It has been hypothesized that environmental exposure to synthetic estrogenic chemicals and related endocrine-active compounds may be responsible for a global decrease in sperm counts, decreased male reproductive capacity, and breast cancer in women. Results of our studies showed that administration of diethylstilbestrol (DES), which had high estrogenic activity, disturbed pregnancy and delivery, and induced hypoplasia of testis and absence of corpora lutena in ovaries in Sprague-Dawley rats. Neonatal administration of DES accelerated mammary carcinogenesis in female rats. Neonatal administration of 4-n-octylphenol (n-OP, 1000μg) which exist in the environment and had a very week estrogenic activity, could not induce endocrine disruption in males and females, but oral administration of high dose (1000ppm) n-OP accelerated mammary carcinogenesis in adult male rats. Therefore, further studies on endocrine disruption of fetal n-OP are necessary.

据推测，环境暴露于合成雌激素化学品和相关的内分泌活性化合物可能是导致全球精子数量减少，男性生殖能力下降和女性乳腺癌的原因。本研究结果表明，具有高雌激素活性的己烯雌酚（DES）给药干扰了Sprague-Dawley大鼠的妊娠和分娩，并导致睾丸发育不全和卵巢黄体缺失。DES的新生儿管理加速乳腺癌的发生在雌性大鼠。环境中存在的雌激素活性很弱的4-正辛基酚（n-OP，1000μg），新生期给药不引起雄性和雌性大鼠内分泌紊乱，但大剂量（1000 ppm）n-OP可加速成年雄性大鼠乳腺癌的发生。因此，有必要进一步研究胎儿n-OP的内分泌干扰作用。

项目成果

Hiroaki Kawaguchi, Hiroki Yoshida, et al.: "Effects of high doses of 17 β-estradiol and ovariectomy on 7,12-Dimethylbenz[a]anthracene-induced mammary carcinomas and dysplasias in neonatally androgenized female Sprague-Dawley rats"Journal of Toxicologic Pa

Hiroaki Kawaguchi、Hiroki Yoshida 等人：“高剂量 17 β-雌二醇和卵巢切除术对新生雄激素化雌性 Sprague-Dawley 大鼠中 7,12-二甲基苯并[a]蒽诱导的乳腺癌和发育不良的影响”毒理学杂志帕

Umekita,Yoshihisa and Yoshida,Hiroki et al.: "Overexpression of cyclin D1 predicts for prognosis in estrogen receptor-negative breast cancer patients"Int. J. Cancer. 98 (in press). (2002)

Umekita, Yoshihisa 和 Yoshida, Hiroki 等人：“细胞周期蛋白 D1 的过度表达可预测雌激素受体阴性乳腺癌患者的预后”Int.

Yoshihisa Umekita,Hiroki Yoshida. et al.: "Co-expression of epidermal growth factor receptor and transforming growth factor-α predicts worse prognosis in breast-cancer patients."Int.J.Cancer (Pred.Oncol.). 89(6). 484-487 (2000)

Yoshihisa Umekita、Hiroki Yoshida 等人：“表皮生长因子受体和转化生长因子-α 的共表达预示着乳腺癌患者的预后较差。”Int.J.Cancer (Pred.Oncol.) 89(6)。 ）484-487（2000）。

Omachi,Katsumi, Yoshida,Hiroki et al.: "Effects of various doses of 17 β -estradiol on the progression of mammary carcinomas induced by single and multiple administration of 7,12-Dimethylbenz)a)anthracene in female rats"Journal of Toxicology Pathology. 13

Omachi、Katsumi、Yoshida、Hiroki 等人：“不同剂量的 17 β-雌二醇对雌性大鼠单次和多次施用 7,12-二甲基苯并）a）蒽诱导的乳腺癌进展的影响”毒理学杂志病理学 13

Kawaguchi,Hiroaki, Yoshida,Hiroki et al.: "Effects of high doses of 17 β-estradiol and ovariectomy on 7,12-Dimethylbenz[ a ]anthracene-induced mammary carcinomas and dysplasias in neonatally androgenized female Sprague-Dawley rats"Journal of Toxicology Pa

Kawaguchi，Hiroaki，Yoshida，Hiroki 等人：“高剂量 17 β-雌二醇和卵巢切除术对新生雄激素化雌性 Sprague-Dawley 大鼠中 7,12-二甲基苯[a]蒽诱导的乳腺癌和发育不良的影响”杂志毒理学帕