Methylsulfonyl metabolites of polychlorinated biphenyl and polybrominated biphenyl as disrupters of endocrine action

多氯联苯和多溴联苯的甲磺酰代谢物作为内分泌作用的干扰物

基本信息

  • 批准号:
    12680549
  • 负责人:
  • 金额:
    $ 2.43万
  • 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:
    2000
  • 资助国家:
    日本
  • 起止时间:
    2000 至 2002
  • 项目状态:
    已结题

项目摘要

1. The results from the present study show that the effects of 3-methylsulfonyl-2, 2', 4', 5-tetrabromobiphenyl (3-MeSO_2-TetraBrB) on the drug-metabolizing enzymes, CYP2B1 and CYP2B2, are several thousand-fold higher than those of parent TetraBrB or phenobarbital, while the effects of its isomeric 4-MeSO_2-TetraBrB are not.2. The present results suggest that 3-MeSO_2-TetraBrB plays an important role in the induction of microsomal drug-metabolizing enzymes by TetraBrB.3. The present findings show that the nine MeSO_2 metabolites of 1, 3-dichlorobenzene (DCB), 1, 2, 4-trichloro-benzene, and tetra-, penta- and hexachlorobiphenyls reduce thyroid hormone levels in rats, suggesting that the metabolites may act as endocrine-disrupters.4. The present results indicate that increase in the hepatic thyroxine (T_4) glucuronidation after the administration of the eight MeSO_2-polychlorinated biphenyls and 3, 5-dichlorophenyl methyl sulfone possibly because of the induction of both UGT1A1 and UGT1A6 caused the reduction of serum T_4 levels.5. The difference in total hepatic concentration of MeSO_2 metabolites among DCB-, 2, 2', 4', 5, 5'-pentachlorobiphenyl-(PentaCB-), 2, 2', 3', 4', 5, 6-hexachlorobiphenyl- (HexaCB-) and Kanechlor-500- (KC500-) treated mice, hamsters, tats and guinea pigs was not correlated with that in the decrease in serum total T_4 level.6. The present findings suggest that the reduction of serum total T_4 level by DCB, HexaCB and KC500 in rats, mice and guines pigs, respectively, would occur at least in part by an increase in T_4 glucuronidation through the induction of hepatic T_4-UDP-glucuronosyltransferase (T_4-UDP-GT), especially UGT1A1 and UGT1A6, while the decrease of serum total T_4 level by PentaCB, TetraBrB and KC500 in mice, hamsters and rats may occur through alternative mechanisms.
1. 本研究结果表明,3-甲基磺酰基- 2,2′,4′,5-四溴联苯(3-MeSO_2-TetraBrB)对药物代谢酶CYP2B1和CYP2B2的影响比亲本TetraBrB或苯巴比多高几千倍,而其异构体4- meso_2 -TetraBrB的影响则没有。目前的结果表明,3-MeSO_2-TetraBrB在诱导微粒体药物代谢酶中起重要作用。本研究结果表明,1,3 -二氯苯(DCB)、1,2,4 -三氯苯和四、五、六氯联苯的九种MeSO_2代谢物可降低大鼠甲状腺激素水平,提示这些代谢物可能具有内分泌干扰物的作用。结果表明,8种meso_2 -多氯联苯和3,5 -二氯苯基甲基砜处理后肝脏甲状腺素(T_4)葡萄糖醛酸化升高可能是由于UGT1A1和UGT1A6的诱导导致血清T_4水平降低。DCB-、2,2′、4′、5,5′-五氯联苯-(PentaCB-)、2,2′、3′、4′、5,6 -六氯联苯-(HexaCB-)和kanechor -500- (KC500-)处理小鼠、仓鼠和豚鼠肝脏中MeSO_2代谢物总浓度的差异与血清总T_4水平的降低无关。本研究结果表明,DCB、HexaCB和KC500对大鼠、小鼠和豚鼠血清总T_4水平的降低,至少部分是通过诱导肝脏T_4- udp -葡萄糖醛酸转移酶(T_4- udp - gt),尤其是UGT1A1和UGT1A6,增加T_4糖醛酸糖醛酸化而发生的,而PentaCB、TetraBrB和KC500对小鼠、仓鼠和大鼠血清总T_4水平的降低可能是通过其他机制发生的。

项目成果

期刊论文数量(47)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yoshihisa Kato: "In vivo metabolism of 2,2',4',5,5'-pentachlorobiphenyl and its inductive activity of drug-metabolizing enzymes : Species difference between rats and mice"Organohalogen Compounds. 49. 213-216 (2000)
加藤嘉久:“2,2,4,5,5-五氯联苯的体内代谢及其药物代谢酶的诱导活性:大鼠和小鼠之间的物种差异”有机卤素化合物。
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    0
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  • 通讯作者:
Yoshihisa Kato.: "Effects of polychlorinated biphenyls (Kanechlor-500) on serum hormone levels in rats and mice"Organohalogen Compounds. 53. 47-49 (2001)
Yoshihisa Kato.:“多氯联苯 (Kanechlor-500) 对大鼠和小鼠血清激素水平的影响”有机卤素化合物。
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    0
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  • 通讯作者:
Yoshihisa Kato: "Reduction of serum thyroxine concentration by methylsulfonyl metabolites of chlorobenzenes in male rats"J.Toxicol.Sci.. 26. 241 (2001)
加藤嘉久:“雄性大鼠中氯苯甲磺酰代谢物降低血清甲状腺素浓度”J.Toxicol.Sci.. 26. 241 (2001)
  • DOI:
  • 发表时间:
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  • 影响因子:
    0
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  • 通讯作者:
Yoshihisa Kato: "3 -Methylsulfonyl-2,2',4',5 -tetrabromobiphenyl, a metabolite of 2,2',4',5-tetrabromobiphenyl induces CYP2B1/2 in rats"Organohalogen Compounds. 49. 209-212 (2000)
Yoshihisa Kato:“3-甲基磺酰基-2,2,4,5-四溴联苯,2,2,4,5-四溴联苯的代谢物在大鼠中诱导 CYP2B1/2”有机卤素化合物。
  • DOI:
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  • 期刊:
  • 影响因子:
    0
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Yoshihisa Kato: "The induction of hepatic microsomal UDP-glucuronosyltransferase by the methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats"Chem, -Biol. Interact.. 125. 107-115 (2000)
Yoshihisa Kato:“大鼠体内多氯联苯同系物的甲磺酰代谢物诱导肝微粒体 UDP-葡萄糖醛酸基转移酶”Chem,-Biol。
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    0
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KATO Yoshihisa其他文献

KATO Yoshihisa的其他文献

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{{ truncateString('KATO Yoshihisa', 18)}}的其他基金

Elucidation of the mechanism for the chemical substances such as polychlorinated biphenyls induced decrease in the serum thyroxine level
阐明多氯联苯等化学物质引起血清甲状腺素水平降低的机制
  • 批准号:
    18K11660
  • 财政年份:
    2018
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study on the exact mechanism for the polychlorinated biphenyl-induced decrease in the serum thyroxine level
多氯联苯引起血清甲状腺素水平降低的确切机制研究
  • 批准号:
    23510083
  • 财政年份:
    2011
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Chemical oceanographic section study of dissolved barium in the western Indian Ocean
西印度洋溶解钡的化学海洋剖面研究
  • 批准号:
    22510018
  • 财政年份:
    2010
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Latitudinal section mapping of pore water constituents in the central and eastern equatorial Pacific
赤道中东太平洋孔隙水成分纬向剖面图
  • 批准号:
    19510014
  • 财政年份:
    2007
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls
多氯联苯降低血清甲状腺素水平的可能机制
  • 批准号:
    18510061
  • 财政年份:
    2006
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of Ba-Si/N diagram in the ocean
海洋中 Ba-Si/N 图的发展
  • 批准号:
    15510010
  • 财政年份:
    2003
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Species differences among mice, hamsters, rats and guinea pigs in PCB-induced alteration of serum thyroid hormone level
PCB引起的血清甲状腺激素水平改变中小鼠、仓鼠、大鼠和豚鼠的物种差异
  • 批准号:
    15510058
  • 财政年份:
    2003
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Comparative paleoceanographical study using piston cores from Okhotsk Basin and Suiko Sea Mount
使用鄂霍次克盆地和Suiko海山的活塞岩心进行比较古海洋学研究
  • 批准号:
    11640491
  • 财政年份:
    1999
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The role of 3-methylsulfony (3-MeSOィイD22ィエD2) metabolites in the induction of hepatic microsomal drug-metabolizing enzymes by PCB congeners, and the toxicological effects of the MeSOィイD22ィエD2 metabolites of PCB congeners
3-甲基磺酰(3-MeSOD22D2)代谢物在PCB同系物诱导肝微粒体药物代谢酶中的作用,以及PCB同系物MeSOD22D2代谢物的毒理学作用
  • 批准号:
    09680531
  • 财政年份:
    1997
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
北西太平洋における海洋古環境の観測タワーとしての孤立海山の利用とその検証
西北太平洋海洋古环境孤立海山观测塔的利用与验证
  • 批准号:
    09640586
  • 财政年份:
    1997
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

Genetic Biomarkers of Polybrominated Biphenyl (PBB)
多溴联苯 (PBB) 的遗传生物标志物
  • 批准号:
    8965041
  • 财政年份:
    2015
  • 资助金额:
    $ 2.43万
  • 项目类别:
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