Formation of Hydroxylated Metabolites Responsible for the Toxicity of Brominated Flame Retardants and Thyroid Hormone Disrupting Action

羟基化代谢物的形成导致溴化阻燃剂的毒性和甲状腺激素干扰作用

• 批准号: 18590118
• 负责人: KITAMURA Shigeyuki
• 金额: $ 2.36万
• 依托单位: Nihon Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590118/
• 关键词: Endocrine disruptor; Brominated flame retardant; Tetrabromobisphenol A; Polybromodiphenyl ether; Thyroid hormonal activity; Estrogenic activity; Metabolic activation; Amphibian metamorphosis; ブロム化難燃剤; ポリブロモジフェニールエーテル; 甲状腺ホルモン; 内分泌撹乱作用

Endocrine-disrupting activity of some brominated flame retardants was examined. 1) The thyroid hormone-disrupting activity of tetrabromobisphenol A, tetrachlorobisphenol A, some 4-hydroxylated polybromodiphenyl ethers was observed in the assay of binding to thyroid hormone receptor. These chemicals also showed thyroid hormonal effect on GH3 cell. However, polybrominated diphenyl ethers and bisphenol A did not exhibit the activity. Especially, tetrabromobisphenol A exhibited the highest thyroid hormonal activity. 3, 5-Substituted bromide is an essential factor for the thyroid hormonal activity. 2) 4-Hydroxy-2, 2', 4-tribromodiphenyl ether exhibited estrogenic activity in the reporter assay using human breast cancer cell line MCF-7. In this case, 3, 5-dibromo substitution decreased the estrogenic activity. 3) The action of these chemicals was also estimated by amphibian metamorphosis using tadpole. The tail of tadopole was shortened by the addition of triiodothyronine (T3). These chemicals showed antagonistic effect against the T3-induced tadpole tail regression. These facts suggest that hydroxylated brominated flame retardants exhibited endocrine-disrupting effect in the worldwide life.

考察了几种含溴阻燃剂的内分泌干扰活性。1)在与甲状腺激素受体结合的实验中，观察到四溴双酚A、四氯双酚A、某些4-羟基多溴二苯醚对甲状腺激素的干扰作用。这些化学物质对GH3细胞也表现出甲状腺激素效应。而多溴二苯醚和双酚A则无此活性。尤其是四溴双酚A表现出最高的甲状腺激素活性。3，5-取代溴是甲状腺激素活性的重要因素。2)4-羟基-2，2‘，4-三溴二苯醚在人乳腺癌细胞株MCF-7的报告实验中显示出雌激素样活性。在这种情况下，3，5-二溴取代降低了雌激素活性。3)利用蝌蚪进行两栖动物变态实验，评价了这些化合物的作用。通过添加三碘甲腺原氨酸(T3)，他多洛尔的尾巴变短。这些化合物对T3诱导的蝌蚪尾巴退化表现出拮抗作用。这些事实表明，羟基溴化阻燃剂在世界范围内具有内分泌干扰作用。

项目成果

Parabens and phthalates : Their metabolism, AhR ligand activity, estrogenic Activity, and P450-inhibitory activity

对羟基苯甲酸酯和邻苯二甲酸盐：它们的代谢、AhR 配体活性、雌激素活性和 P450 抑制活性

• 发表时间: 2007
• 作者: H.;Oz-aki;S.;Shinohara;S.;Tange;K.;Sugihara;S.;Kitamura;S.;Ohta
• 通讯作者: Ohta

Suppression of amphibian metamorphosis by bisphenol A and related chemical substances

• DOI: 10.1248/jhs.52.160
• 发表时间: 2006-04-01
• 期刊: JOURNAL OF HEALTH SCIENCE
• 作者: Goto, Y;Kitamura, S;Kashiwagi, A
• 通讯作者: Kashiwagi, A

Effects of environmental antiandrogenic chemicals on expression of androgen-responsive genes in rat prostate lobes

环境抗雄激素化学物质对大鼠前列腺叶雄激素反应基因表达的影响

• 发表时间: 2007
• 期刊: Journal of Health Sciences 53
• 作者: Suzuki;et. al.
• 通讯作者: et. al.

Novel metabolic pathways ofp-n-nonylphenol catalyzed by cytochrome P450 and estrogen recentor bindina activity of new metabolites

细胞色素P450催化对正壬基苯酚的新代谢途径和新代谢物的雌激素受体结合活性

• 发表时间: 2007
• 期刊: Journal of Health Science 53(5)
• 作者: Shigeru;Ohta;Shigeo;Nakamura;Tadahiko;Mashino
• 通讯作者: Mashino

4-Hydroxy-3, 5, 3', 4'-tetrachlorobiphenyl induced membrane permeability transition in isolated rat liver mitochondria

4-羟基-3,5,3,4-四氯联苯诱导离体大鼠肝线粒体膜通透性转变

• 发表时间: 2006
• 期刊: J. Clin. Biochem. Nutr. 38
• 作者: K.;Utsumi
• 通讯作者: Utsumi