Thyroid hormone-disrupting activity of brominated retardants and hydroxylated PCBs
Thyroid hormone-disrupting activity of brominated retardants and hydroxylated PCBs
批准号:
16590092
负责人:
KITAMURA Shigeyuki
金额:
$2.24万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2004
资助国家:
日本
项目状态:
已结题
起止时间:
2004 至 2005
中文摘要
用大鼠垂体细胞系(GH 3)和中国仓鼠卵巢细胞系(CHO-K1)进行报告基因测定,估计双酚A衍生物和某些多氯联苯的甲状腺功能破坏活性。四溴双酚A(TBBPA)、四氯双酚A、4-羟基-2,2 ',3,4',5,5 '-六氯联苯、4-羟基-3,3',4 ',5-四氯联苯和4,4'-二羟基-3,3 ',5,5'-四氯联苯对GH 3细胞有甲状腺激素效应。而4-羟基-2,2 ',5,5'-四氯联苯、4-羟基-2 ',4',6 '-三氯联苯、3-羟基-2,2',5,5 '-四氯联苯、2,3',5,5 '-四氯联苯和双酚A则不显示活性。特别是,TBBPA,阻燃剂,表现出最高的甲状腺激素活性。相反,这些化学物质对转染甲状腺激素受体(TR)的CHO-K1细胞中三碘甲状腺原氨酸(T3)的活性表现出抗甲状腺激素作用。3,5-取代的溴化物或氯是甲状腺激素干扰活性的重要因素。这些化学品的行动也估计了两栖类变态蝌蚪。T3的加入使蝌蚪的尾巴变短。这些化合物对T3诱导的蝌蚪尾退化有拮抗作用。这些事实表明,溴化阻燃剂,TBBPA和羟基化多氯联苯表现出内分泌干扰作用的野生动物。
英文摘要
The thyroid hormone-disrupting activity of bisphenol A derivatives and some PCBs was estimated by the reporter assay using a rat pituitary cell line (GH3) and a Chinese hamster ovary cell line (CHO-K1). Tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A, 4-hydroxy-2,2',3,4',5,5'-hexachiorobiphenyl, 4-hydroxy-3,3',4',5-tetrachlorobiphenyl and 4,4'-dihydroxy-3,3',5,5'-tetrachlorobiphenyl showed thyroid hormonal effect on GH3 cells. However, 4-hydroxy-2,2',5,5'-tetrachlorobiphenyl, 4-hydroxy-2',4',6'-trichlorobiphenyl, 3-hydroxy-2,2',5,5'-tetrachlorobiphenyl, 2,3',5,5'-tetrachlorobiphenyl and bisphenol A did not exhibit the activity. Especially, TBBPA, a flame retardant, exhibited the highest thyroid hormonal activity. In contrast, these chemicals showed anti-thyroid hormone effects on the activity of triiodothyronine (T3) in CHO-K1 cells transfected with thyroid hormone receptor (TR). 3,5-Substituted bromide or chlorine is an essential factor for the thyroid hormone-disrupting activity. The action of these chemicals was also estimated by amphibian metamorphosis using tadpole. The tail of tadpole was shortened by the addition of T3. These chemicals showed antagonistic effect on the T3-induced tadpole tail regression. These facts suggest that a brominated flame retardant, TBBPA, and hydroxylated PCBs exhibit endocrine-disrupting action in the wildlife.
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DOI:
10.1016/j.taap.2004.07.005
发表时间:
2005-02-15
期刊:
TOXICOLOGY AND APPLIED PHARMACOLOGY
影响因子:
3.8
作者:
[Suzuki, T, Kitamura, S, Ohta, S]
通讯作者:
Ohta, S
DOI:
10.1016/j.lfs.2004.08.030
发表时间:
2005-02-18
期刊:
LIFE SCIENCES
影响因子:
6.1
作者:
[Kitamura, S, Kato, T, Kashiwagi, A]
通讯作者:
Kashiwagi, A
DOI:
10.1093/toxsci/kfi074
发表时间:
2005-04-01
期刊:
TOXICOLOGICAL SCIENCES
影响因子:
3.8
作者:
[Kitamura, S, Suzuki, T, Ohta, S]
通讯作者:
Ohta, S
DOI:
10.1124/dmd.104.002634
发表时间:
2005-08-01
期刊:
DRUG METABOLISM AND DISPOSITION
影响因子:
3.9
作者:
[Kohno, Y, Kitamura, S, Ohta, S]
通讯作者:
Ohta, S
DOI:
10.1016/j.bbrc.2004.04.066
发表时间:
2004-05-28
期刊:
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
影响因子:
3.1
作者:
[Sugihara, K, Kitamura, S, Matsuda, T]
通讯作者:
Matsuda, T
共 9 条
Determination of targets for thyroid hormone disruption by brominated flame retardants
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批准号:22510071
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项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.91万
-
财政年份:2011
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负责人:KITAMURA Shigeyuki
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依托单位:
Formation of Hydroxylated Metabolites Responsible for the Toxicity of Brominated Flame Retardants and Thyroid Hormone Disrupting Action
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批准号:18590118
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.36万
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财政年份:2006
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负责人:KITAMURA Shigeyuki
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依托单位:
Metabolic activation of endocrine-disruptors in animal body
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批准号:13672343
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.24万
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财政年份:2001
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负责人:KITAMURA Shigeyuki
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依托单位:
Metabolism and endocrine disrupting action of environmental pollutants
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批准号:11557199
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项目类别:Grant-in-Aid for Scientific Research (B).
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资助金额:$7.87万
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财政年份:1999
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负责人:KITAMURA Shigeyuki
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依托单位:
海外基金