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Species difference in hydroxylation of polychlorinated biphenyls and exposure of metabolites in human blood.

Research Project

Project/Area Number 16590101
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionDaiichi College of Pharmaceutical Sciences

Principal Investigator

HARAGUCHI Koichi  Daiichi College of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00258500)

Co-Investigator(Kenkyū-buntansha) NISHIMURA Eri  Daiichi College of Pharmaceutical Sciences, Research Associate, 薬学部, 助手 (80412550)
青島 理恵  第一薬科大学, 薬学部, 助手
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsPCB / hydroxylated metabolites / human / blood / species difference / catechol / カテコール代謝物 / Gunnラット / ハムスター / GC-MS / UGT活性
Research Abstract

1. In the hydroxylation metabolism of polychlorinated biphenyls (PCBs), species differences were studied in rats, mice, hamsters and guinea pigs dosed with PCB mixture (Kanechlor 500). Catechol PCBs (mainly di0H-CBH0) were highly produced in hamsters, while hydroxylated PCBs (mainly 4-OH-CB 107) and methylsulfonyl PCBs were preferably produced in rats and mice. Guinea pigs produced methylsulfonyl-hydroxylated PCBs. All diOH-PCBs were found to be derived from 2,5-or 2,3,6-chlorinated PCBs.
2. The in vitro metabolism of PCB 101 was studied using liver microsomes of rats, hamsters and guinea pigs.3-0H-, 3'-OH-, 4'-OH-and 3',4'-di0H-CB101 were formed by liver microsomes of rats and guinea pigs. The formation of di0H-CB101 from 3'-OH-and 4'-0H-CB101 proceeded at much higher rate than that from CB101 and was accelerated by phenobarbital-treatment. The result indicated that the metabolism of CB 101 to di0H-CB101 is principally catalyzed by CYP2B enzymes, which prefer 4'-0H-and 3'-OH to CB101.
3. Hydroxyl Ted PCBs retained in human blood were found to be 4-0H-CB107, 4-0H-CB146 and 4-0H-CB187.In order to further investigate the body burden of di0H-PCBs in human, blood samples from Fukuoka residents were analyzed by electron capture negative ionization-gas chromatography-mass spectrometry (ECNI-GC), using 18 synthesized references (veratrolic PCBs) for catechol metabolites. As a result, one di0H-PCB was detected in human blood, and identified as 4,5-(OH)_2-2,3,6,2',4',5'-hexaCB (di0H-CB149).Further monitoring and toxicological significance of hydroxylated PCBs including catecholic PCBs should be performed, since these metabolites may decrease the thyroxine levels in human body.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (33 results)

All 2007 2006 2005 2004

All Journal Article (33 results)

  • [Journal Article] Metabolism of 2,2',4,5,5'-pentachlorobiphenyl (CB101) by liver microsomes of rats, hamsters and guinea pigs.2007

    • Author(s)
      太田千穂
    • Journal Title

      福岡医学雑誌 (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Metabolism of 2,2',4,5,5'-pentachlorobiphenyl (CB101) by liver microsomes of rats, hamsters and guinea pigs.2007

    • Author(s)
      C.Ohta, M.Matsuoka, K.Haraguchi, Y.Kato, T.Endo, N.Koga
    • Journal Title

      Fukuoka Acta Med. 97(in press)

    • NAID

      120000987159

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fungal bioconversion of toxic polychlorinated biphenyls by white-rot fungus, Phlebia brevispora.2006

    • Author(s)
      I.Kamei
    • Journal Title

      Appl. Microbiol. Biotechnol. 73

      Pages: 932-940

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 2,2',3,4',5,5'-七塩素化ビフェニル(CB187)の主代謝物の合成2006

    • Author(s)
      太田千穂
    • Journal Title

      中村学園大学・中村学園短期大学部研究紀要 38

      Pages: 197-201

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fungal bioconversion of toxic polychlorinated biphenyls by white-rot fungus, Phlebia brevispora.2006

    • Author(s)
      I.Kamei, S.Sonoki, K.Haraguchi, R.Kondo
    • Journal Title

      Appl. Microbiol. Biotechnol. 73

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Synthesis of major metabolites of 2,2',3,4',5,5',6-heptachlorobiphenyl (CB187).2006

    • Author(s)
      C.Ohta, K.Haraguchi, M.Ozaki, M.Matsuoka, N.Koga
    • Journal Title

      Bull. Nakamura Gakuen Univ. and Nakakura Gakuen Junior College. 38

      Pages: 197-201

    • NAID

      110006405532

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 2,2',3,4',5,5',6-七塩素化ビフェニル(CB187)の主代謝物の合成2006

    • Author(s)
      太田千穂
    • Journal Title

      中村学園大学 研究紀要 38

      Pages: 197-201

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Concentration of dioxins and related compounds in the blood of Fukuoka residents.2005

    • Author(s)
      Y.Masuda
    • Journal Title

      Chemosphere 58

      Pages: 329-344

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 2,3',4,4',5-五塩素化ビフェニル(CB118)のモルモット肝ミクロゾームによる 代謝2005

    • Author(s)
      太田千穂
    • Journal Title

      福岡医学雑誌 96

      Pages: 232-240

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Species differences in the tissue distribution of catechol and methylsulfonyl metabolites of 2,4,5,2',5'-penta- and 2,3,4,2',3',6'-hexachlorobiphenyl in rats, mice, hamsters and guinea pig.2005

    • Author(s)
      K.Haraguchi
    • Journal Title

      Xenobiotica 35

      Pages: 85-96

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Comparative metabolism of polychlorinated biphenyls and tissue distribution of persistent metabolites in rats, hamsters and guinea pigs.2005

    • Author(s)
      K.Haraguchi
    • Journal Title

      Drug Metab. Dispos. 33

      Pages: 373-380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vitro metabolism of 2,2',3,4',5',6-heptachloro- biphenyl (CB187) by liver microsomes from rats, hamsters and guinea pigs.2005

    • Author(s)
      C.Ohta
    • Journal Title

      Xenobiotica 35

      Pages: 319-330

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The decrease in level of serum thyroxine by 2,2',4,5,5'-pentachlorobiphenyl in rats and mice : No correlation with formation of methylsulfonyl metabolites.2005

    • Author(s)
      Y.Kato
    • Journal Title

      Drug. Metab. Dispos. 33

      Pages: 1611-1665

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Concentrations of dioxins and related compounds in the blood of Fukuoka residents.2005

    • Author(s)
      Y.Masuda, K.Haraguchi, S.Kono, H.Tsuji, 0.Papke
    • Journal Title

      Chemosphere 58

      Pages: 329-344

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Metabolism of 2, 3', 4, 4', 5-pentachlorobiphenyl in guinea pig microsomes2005

    • Author(s)
      C.Ohta, K.Haraguchi, Y.Kato, N.Koga.
    • Journal Title

      Fukuoka Acta Med. 96

      Pages: 232-240

    • NAID

      120002834566

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Species differences in the tissue distribution of catechol and methylsulphonyl metabolites of 2,4,5,2',5'-penta-and 2,3,4,2',3',6'-hexachloro-biphenyl in rats, mice, hamsters and guinea pigs.2005

    • Author(s)
      K.Haraguchi, Y.Kato, N.Koga, M.Degawa
    • Journal Title

      Xenobiotica 35

      Pages: 85-96

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Comparative metabolism of polychlorinated biphenyls and tissue distribution of persistent metabolites in rats, hamsters and guinea pigs.2005

    • Author(s)
      K.Haraguchi, N.Koga, Y.Kato
    • Journal Title

      Drug Metab. Dispos. 33

      Pages: 373-380

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vitro metabolism of 2,2',3,4',5,5',6-heptachlorobiphenyl (CB187) by liver microsomes from rats, hamsters and guinea pigs.2005

    • Author(s)
      C.Ohta, K.Haraguchi, Y.Kato, N.Koga
    • Journal Title

      Xenobiotica 35

      Pages: 319-330

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The decrease in level of serum thyroxine by 2,2',4,5,5'-pentachlorobiphenyl in rats and mice : No correlation with formation of methylsulfonyl metabolites.2005

    • Author(s)
      Y.Kato, K.Haraguchi, T.Yamazaki, R.Kimura, N.Koga, S.Yamada, M.Degawa
    • Journal Title

      Drug Metab. Dispos. 33

      Pages: 1661-1665

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 2,3',4,4'5-五塩素化ビフェニル(CB118)のモルモット肝ミクロソームによる代謝2005

    • Author(s)
      太田千穂
    • Journal Title

      福岡医学雑誌 96

      Pages: 232-240

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 油症患者体内のPCBおよびPCDFの35年間の挙動と毒性影響2005

    • Author(s)
      増田義人
    • Journal Title

      福岡医学雑誌 96

      Pages: 113-123

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The decrease in levels of serum thyroxine by 2,2',4,4',5,5'- pentachlorobiphenyl in rats and mice: No correlation with formation of methylsulfonyl metabolites2005

    • Author(s)
      Y.Kato
    • Journal Title

      Drug Metabolism and Disposition 33

      Pages: 1661-1665

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Comparative metabolism of polychlorinated biphenyls and tissue distribution of persistent metabolites in rats, hamsters and guinea pigs.2005

    • Author(s)
      K.Haraguchi
    • Journal Title

      Drug Metabolism and Disposition 33

      Pages: 373-380

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Species differences in tissue distribution of catechol and methylsulphonyl metabolites of polychlorinated biphenyls in rats, mice, hamsters and guinea pigs.2005

    • Author(s)
      K.Haraguchi
    • Journal Title

      Xenobiotica 35

      Pages: 85-96

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vitro metabolism of 2,2',3,4',5,5',6-heptachlorobiphenyl (CB187) by liver microsomes from rats, hamsters and guinea pigs.2005

    • Author(s)
      C.Ohta
    • Journal Title

      Xenobiotica (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Metabolism of polychlorinated biphenyls by Gun rats : identification and serum retention of catechol metabolites.2004

    • Author(s)
      K.Haraguchi
    • Journal Title

      Chem. Res. Toxicol. 17

      Pages: 1684-1691

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats.2004

    • Author(s)
      Y.Kato
    • Journal Title

      Toxicol. Sci. 81

      Pages: 309-315

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors2004

    • Author(s)
      KJ.Gauger
    • Journal Title

      Environ. Health Oerspect. 112

      Pages: 516-523

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Metabolism of polychlorinated biphenyls by Gunn rats : Identification and serum retention of catechol metabolites.2004

    • Author(s)
      K.Haraguchi, Y.Kato, N.Koga, M.Degawa
    • Journal Title

      Chem. Res. Toxicol. 17

      Pages: 1684-1691

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats.2004

    • Author(s)
      Y.Kato, S.Ikushiro, K.Haraguchi, T.Yamazaki, Y.Ito, H.Suzuki, R.Kimura, S.Yamada, T.Inoue, M.Degawa
    • Journal Title

      Toxicol. Sci. 81

      Pages: 309-315

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors.2004

    • Author(s)
      KJ.Gauger, Y.Kato, K.Haraguchi, H-J.Lehmler, LW.Robertson, R.Bansal, RT.Zoeller
    • Journal Title

      Environ. Health Perspect. 112

      Pages: 516-523

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats2004

    • Author(s)
      Y.Kato
    • Journal Title

      Toxicological Science 81

      Pages: 309-315

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Metabolism of polychlorinated biphenyls by Gunn rats ; Identification and serum retention of catechol metabolites2004

    • Author(s)
      K.Haraguchi
    • Journal Title

      Chemical Research in Toxicology 17

      Pages: 1684-1691

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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