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Study of the mechanism of developmental toxicology by dioxin with cDNA microarray analysis

Research Project

Project/Area Number 14560254
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionRakuno Gakuen University

Principal Investigator

TERAOKA Hiroki  Rakuno Gakuen University, School of Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (50222146)

Co-Investigator(Kenkyū-buntansha) UENO Naoto  National Institute for Basic Biology, Deparment of Developmental Biology, Professor, 基礎生物学研究所, 教授 (40221105)
ENDOH Daiji  Rakuno Gakuen University, School of Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (40168828)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordszebrafish / Xenopus laevis / TCDD / developmental toxicology / arylhydrocarbon receptor / circulation failure / cytochrome P450 1A / cyclooxygenase 2 / マイクロアレイ / 循環障害 / 頭部顔面奇形 / ソニックヘッジホッグ / COX2
Research Abstract

1)We carried out the extensive macmarray analysis with forty thousand clones for Xenopus laevis (Xenopus) to investigated the mechanism of 2,3,7,8-tetrachlomdibenzo-gdioxin (TODD). TODD caused induction of 1 done and reduction of 5 clones at 27 hours post fertilization (hpf), induction of 41 clones at 7 dpf and induction of 14 clones and reduction of 42 clones. However, we mould not find any done, which was confirmed with northern blot analysis except cytochmme P4501A(CYP1A6, 7).
2)We originally cloned a cDNA of arylhydrocarbon receptor from Xenopus (xAHR). xAHR was already expressed from ldpf and was increased by 7dpf with concomitant induction of CYP1A6 and 7 by TCDD. While CYP1B was induced, Arnt and glutathion transferase was not affected by TCDD treatment.
3)Injection with either AHR2 morpholino (AHR2-MO) or CYP1A morpholino (CYP1A-MO) blocked induction of CYP1A protein in the vascular endothelium and protected against all endpoints of TCDD developmental toxicity already observed in … More cluding circulation failure and impairement of lower jaw growth. For all observations, CYP1A-MO was more effective against the higher TCDD concentrations than AHR2-MO. These suggest that AHR2-mediated CYP1A induction in the vascular endothelium of the zebrafish embryo is involved in various toxicity elicited by TCDD.
4)TCDD-inducecl mesencephalic circulation failure was markedly inhibited by selective COX2 inhibitors but not by selective COX1 inhibitor and a selective 5-lipoxygenase (5-LOX) inhibitor. Morpholino antisense oligos against COX2 (COX2-MO) also recovered mesencephalic circulation failure by TCDD. Furthermore, TCDD-induced apoptosis in dorsal midbrain was also abolished by both COX2 inhibitor and COX2-MO. COX2 transcripts were detected in some vessels including carotid artery, while the expression was not affected by TCDD. These results suggest the involvement of COX2 in TCDD-induced mesencephalic circulation failure in developing zebrafish.
5)Zebrafish developing lower jaw expresses Sonic hedgehog (Shh), Tiggy"winkle hedgehog (Twhh) and their receptors as well as their transcription factors. Shh function-defective mutant or normal larva treated with cyclopamine, an inhibitor for hedgehog signaling showed marked retardation of jaw growth. Larvae treated with TCDD also exhibiting jaw retardation showed a marked reduction of Shh and Twhh expression in the developing lower jaw, although transcripts of their receptors and transcriptional factors were hardly affected. AHR2-MO inhibited the reduction of hedgehog expression as well as the typical macroscopic endpoints of TCDD toxicity. These results suggest a reduction in Shh by TCDD exposure occurs postactivation of the AHR pathway and possible contribution to the adverse effects on the development of the jaw. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (39 results)

All 2005 2004 2003 2002 Other

All Journal Article (30 results) Publications (9 results)

  • [Journal Article] Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphe neurones and cranial motoneurones.2005

    • Author(s)
      Norton WH, Mangoli M, et al.
    • Journal Title

      Development 132

      Pages: 645-658

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Zebrafish as a Model Vertebrate for Investigating Chemical Toxicity2005

    • Author(s)
      Hill AJ, Teraoka-H, et al.
    • Journal Title

      Toxicological Sciences (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mechanism of cell death in inflamed superficial digital flexor tendon in the horse.2005

    • Author(s)
      Hosaka Y, Teraoka H, Yamamoto E, Ueda H, Takehana K
    • Journal Title

      Journal of Comparative Pathology 132

      Pages: 51-58

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Oxidative stress and apoptosis induced by tributyltin in retinal neuronal cels of developing zebrafish.2005

    • Author(s)
      Dogn W, Muramoto W, et al.
    • Journal Title

      Aquatic Toxicology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mechanism of cell death in inflamed superficial digital flexor tendon in the horse.2005

    • Author(s)
      Hosaka Y, Teraoka H, Yamamoto E, Ueda H, Takehana K
    • Journal Title

      J Comp Pathol. 132

      Pages: 51-58

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphe neurones and cranial motoneurones.2005

    • Author(s)
      Norton WH, Mangoli M.et al.
    • Journal Title

      Development 132

      Pages: 645-658

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Zebrafish as a model vertebrate for Investigating Chemical Toxicity2005

    • Author(s)
      Hill AJ, Teraoka-H et al.
    • Journal Title

      Toxicological Sciences (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Oxidative stress and apoptosis induced by tributyltin in retinal neuronal cells of developing zebrafish.2005

    • Author(s)
      Dong W, Muramoto W.et al.
    • Journal Title

      Aquatic Toxicology (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Role of aryl hydrocarbon receptor in mesencephalic circulation failure and apoptosis in zebrafish embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin2004

    • Author(s)
      Dong-W, Teraoka-H, et al.
    • Journal Title

      Toxicological Sciences 77

      Pages: 109-116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hedgehog and Fgf signaling pathways regulate the development of tphR-expressing serotonergic raphe neurons in zebrafish embryos2004

    • Author(s)
      Teraoka-H, Russel-C, et al.
    • Journal Title

      Journal of Neurobiology 60

      Pages: 275-288

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Decreased apoptosis of beta2-integrin-deficient bovine neutrophils.2004

    • Author(s)
      Nagahata-H, Higuchi-H, et al.
    • Journal Title

      Immunology and Cell Biology 82

      Pages: 32-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hedgehog and Fgf signaling pathways regulate the development of tphR-expressing serotonergic raphe neurons in zebrafish embryos.2004

    • Author(s)
      Teraoka H, Russell C, Regan J, Chandrasekhar A, Concha ML, Yokoyama R, Higashi K, Take-Uchi M, Dong W, Hiraga T, Holder N, Wilson SW
    • Journal Title

      J Neurobiol. 60

      Pages: 275-288

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Role of aryl hydrocarbon receptor in mesencephalic circulation failure and apoptosis in zebrafish embryos exposed to 2,3,7,8-tetrachlorodibenzo -p-dioxin.2004

    • Author(s)
      Dong W, Teraoka H, Tsujimoto Y, Stegeman JJ, Hiraga T
    • Journal Title

      Toxicol Sci. 77

      Pages: 109-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Monorail/FoxA2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphe neurons and cranial motor neurons.2004

    • Author(s)
      Norton W, Mangoli M, Lele Z, Pagoda H-M, Diamond B, Russell C, Teraoka H, Stickney H, Rauch G-J, Heisenberg C-P, Houart C, Schilling T, Frohnhoefer HG, Rastegar S, Neumann C, Gardiner M, Strahle U, Geisler R, Rees M, Talbot W, Wilson SW
    • Journal Title

      Development 132

      Pages: 645-658

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Decreased apoptosis of beta 2-integrin-deficient bovine neutrophils.2004

    • Author(s)
      Nagahata H, Higuchi H, Teraoka H, Takahashi K, Inanami O, Kuwabara M
    • Journal Title

      Immunol Cell Biol. 82

      Pages: 32-37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hedgehog and Fgf signaling pathways regulate the development of tphR-expressing serotonergic raphe neurons in zebrafish embryos.2004

    • Author(s)
      Teraoka-H, Russel-C.et al.
    • Journal Title

      Journal of Neurobiology 60

      Pages: 275-288

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Induction of cytochrome P450 1A is required for circulation failure andedema by 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish2003

    • Author(s)
      Teraoka H, Dong W, Tsujimoto Y, Iwasa H, Endoh D, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 304

      Pages: 223-228

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Zebrafish as a novel experimental model for developmental Toxicology2003

    • Author(s)
      Teraoka-H, Dong-W, et al.
    • Journal Title

      Congenital Anomaly (Kyoto) 43

      Pages: 123-132

    • NAID

      110002785608

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Aryl hydrocarbon receptor 2 mediates 2,3,7,8-tetrachlorodibenzo-p-dioxin developmental toxicity in zebrafish2003

    • Author(s)
      Prasch-AL, Teraoka-H et al.
    • Journal Title

      Toxicological Sciences 76

      Pages: 138-150

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of cytochrome P450 1A is required for circulation failure and edema by 2,3,7,8-tetrachlorodibenzo- p-dioxin in zebrafish.2003

    • Author(s)
      Teraoka H, Dong W, Tsujimoto Y, Iwasa H, Endoh D, Ueno N, Stegeman JJ, Peterson RE, Hiraga T
    • Journal Title

      Biochem Biophys Res Commun. 304

      Pages: 223-228

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Aryl hydrocarbon receptor 2 mediates 2,3,7,8-tetrachlorodibenzo-p-dioxin developmental toxicity in zebrafish.2003

    • Author(s)
      Prasch AL, Teraoka H, Carney SA, Dong W, Hiraga T, Stegeman JJ, Heideman W, Peterson RE
    • Journal Title

      Toxicol Sci. 76

      Pages: 138-150

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Zebrafish as a novel experimental model for developmental toxicology.2003

    • Author(s)
      Teraoka H, Dong W, Hiraga T
    • Journal Title

      Congenit Anom. (Review) 43

      Pages: 123-132

    • NAID

      110002785608

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity in the zebrafish embryo: altered regional blood flow and impaired lower jaw development.2002

    • Author(s)
      Teraoka H, Dong W, Ogawa S, et al.
    • Journal Title

      Toxicological Sciences 65

      Pages: 192-199

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 2,3,7,8-Tetrachloridibenzo-p-dioxin toxicity in the zebxafish embryo: Local circulation failure in the dorsal midbrain is associated with in creased apoptosis.2002

    • Author(s)
      Dong W, Teraoka H, Yamazaki K, Tsukiyama S, Imani S, et al.
    • Journal Title

      Toxicological Sciences 69

      Pages: 191-201

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] cDNA cloning and expressions of cytochrome P450 1A in zebrafish embryos2002

    • Author(s)
      Yamazaki K, Teraoka H, Dong W, Stegeman JJ, Hiraga T
    • Journal Title

      Journal of Veterinary Medical Science 64

      Pages: 829-833

    • NAID

      110003920947

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity in the zebrafish embryo altered regional blood flow and impaired lower jaw development.2002

    • Author(s)
      Teraoka H, Dong W, Ogawa S, Tsukiyama S, Okuhara Y, Niiyama M, Ueno N, Peterson RE, Hiraga T
    • Journal Title

      Toxicol Sci. 65

      Pages: 192-199

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in the zebrafish embryo : local circulation failure in the dorsal midbrain is associated with increased apoptosis.2002

    • Author(s)
      Dong W, Teraoka H, Yamazaki K, Tsukiyama S, Imani S, Imagawa T, Stegeman JJ, Peterson RE, Hiraga T
    • Journal Title

      Toxicol Sci. 69

      Pages: 191-201

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] cDNA cloning and expressions of cytochrome P450 IA in zebrafish embryos.2002

    • Author(s)
      Yamazaki K, Teraoka H, Dong W, Stegeman JJ, Hiraga T
    • Journal Title

      J Vet Med Sci. 64

      Pages: 829-833

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Oxidative stress and apoptosis induced by tributyltin in retinal neuronal cells of developing zebrafish.

    • Author(s)
      Dong W, Muramoto W, Takehana K, Stegem JJ, Teraoka H, Hiraga T
    • Journal Title

      Aquatic Toxicol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Zebrafish as a Model Vertebrate for Investigating Chemical Toxicity.

    • Author(s)
      Hill AJ, Teraoka H, Heideman W, Peterson RE
    • Journal Title

      Toxicol Sci. (Review) (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Teraoka-H, Dong-W et al.: "Induction of cytochrome P450 1A is required for circulation failure and edema by 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish."Biochem Biophys Res Commun. 304. 223-228 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Teraoka-H, Dong-W et al.: "Zebrafish as a novel experimental model for developmental toxicology"Congenit Anom Kyoto.. 43. 123-132 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Prasch-AL, Teraoka-H et al.: "Aryl hydrocarbon receptor 2 mediates 2,3,7,8-tetrachlorodibenzo-p-dioxin developmental toxicity in zebrafish"Toxicol Sci.. 76. 138-150 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Dong-W, Teraoka-H.: "Role of aryl hydrocarbon receptor in mesencephalic circulation failure and apoptosis in zebrafish embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin"Toxicol.Sci.. 77. 109-116 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Teraoka-H, Russel-C.: "Hedgehog and Fgf signaling pathways regulate the development of tphR-expressing serotonergic raphe neurons in zebrafish Embryos"J.Neurobiol.. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nagahata-H, Higuchi-H.: "Decreased apoptosis of beta2- integrin-deficient bovine neutrophils."Immunol.Cell Biol.. 82. 32-37 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Dong W, Teraoka H, Yamazaki K, Tsukiyama S, Imani S, et al.: "2,3,7,8-Tetrachloridibenzo-p-dioxin toxicity in the zebrafish embryo : Local circulation failure in the dorsal midbrain is assocaited with increased apoptosis"Toxicological Sciences. 69(1). 191-201 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamazaki K, Teraoka H, Dong W, Stegeman JJ, Hiraga T.: "cDNA cloning and expressions of cytochrome P450 1A in zebrafish embryos"Journal of Veterinary Medical Science. 64(9). 829-833 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Teraoka H, Dong W, Tsujimoto Y, Iwasa H, Endoh D, et al.: "Induction of cytochrome P450 1A is required for circulation failure and edema by 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish"Biochemical and Biophysical Research Communications. (in press).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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