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2008 Fiscal Year Final Research Report

Biological function of aryl hydrocarbon receptors in the hematopoietic progenitor cells with respect to a possible toxicologic mechanism

Research Project

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Project/Area Number 18510066
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionNational Institute of Health Sciences

Principal Investigator

INOUE Tohru  National Institute of Health Sciences, 安全性生物試験研究センター, センター長 (50100110)

Co-Investigator(Kenkyū-buntansha) HIRABAYASHI Yoko  国立医薬品食品衛生研究所, 安全性生物試験研究センター毒性部, 室長 (30291115)
TSUBOI Isao  日本大学, 医学部, 講師 (30350028)
Research Collaborator YOON Byung-il  韓国江原大学校, 獣医学部, 准教授
Project Period (FY) 2006 – 2008
KeywordsAh受容体 / 造血幹細胞 / 遺伝子改変動物 / 細胞周期 / CYP2E1 / Ah受容体ノックアウトマウス / ベンゼン / ベンゼン代謝物
Research Abstract

骨髄では、アリールハイドロカーボン受容体(AhR)が、造血前駆細胞特異的に発現しており、同時に個々に特異的に発現するcytochrome p450 2E1(CYP2E1)の関与が、ベンゼンの毒性発現機構をなしている。これに基づいて、ベンゼンの影響を参照しつつ、
(1)AhRが分子進化に果たした役割、
(2)AhRの造血前駆細胞の細胞周期制御に対する役割、及び
(3)その異物相互作用の上での役割の3点を明らかにした。

  • Research Products

    (48 results)

All 2009 2008 2007 2006 Other

All Journal Article (15 results) Presentation (30 results) Book (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Aryl hydrocarbon receptor biology and xenobiotic responses in hematopoietic progenitor cells.2009

    • Author(s)
      Hirabayashi Y、Inoue T.
    • Journal Title

      Biochem Pharmacol 77

      Pages: 521-35

  • [Journal Article] Comparison of murine gene expression profiles between spontaneous and radiation- induced myelogenous leukemias : Stochastic and probabilistic expression variances in the former vs radiation-specific expression commonalities in the latter.2009

    • Author(s)
      Hirabayashi Y、Tsuboi I、(6名省略)、Inoue T.
    • Journal Title

      Exp Hematol 37

      Pages: 195-205

  • [Journal Article] AhR-mediated benzene-induced hematopoietic toxicities: differential toxicities between one from AhR in the hematopoietic stem cells for the bone marrow and the other from possible hepatic- AhR for the peripheral blood.2008

    • Author(s)
      Hirabayashi Y、Yoon BI、(4名省略)、Inoue T.
    • Journal Title

      Organohalogen Compounds 70

      Pages: 287-290

  • [Journal Article] Benzene-induced hematopoietic toxicity transmitted by AhR in wild-type mouse and nullified by repopulation with AhR-deficient bone marrow cells: time after benzene treatment and recovery.2008

    • Author(s)
      Hirabayashi Y、Yoon BI、(4名省略)、Inoue T.
    • Journal Title

      Chemosphere 73

      Pages: S290-4

  • [Journal Article] Implications of hemopoietic progenitor cell kinetics and experimental leukemogenesis: Relevance to Gompertzean mortality as possible hematotoxicological endpoint.2007

    • Author(s)
      Hirabayashi Y、Inoue T.
    • Journal Title

      Exp Hematol 35

      Pages: 125-33

  • [Journal Article] Membrane Channel Connexin 32 Maintains Lin(-)/c-kit (+) Hematopoietic Progenitor Cell Compartment: Analysis of the Cell Cycle.2007

    • Author(s)
      Hirabayashi Y、Yoon BI、Tsuboi I、(5名省略)、Inoue T.
    • Journal Title

      J Membr Biol 217

      Pages: 105-113

  • [Journal Article] Protective role of connexin 32 in steady-state hematopoiesis、regeneration state、and leukemogenesis.2007

    • Author(s)
      Hirabayashi Y、Yoon BI、Tsuboi I、(5名省略)、Inoue T.
    • Journal Title

      Exp Biol Med (Maywood) 232

      Pages: 700-12

  • [Journal Article] Aryl hydrocarbon receptor suppresses spontaneous neoplasms and extends life span : possible mechanism implied by hematopoietic stem cell kinetics.2007

    • Author(s)
      Hirabayashi Y、Yoon BI、(3名省略)、Inoue T.
    • Journal Title

      Organohalogen Compounds 69

      Pages: 357-361

  • [Journal Article] p53 (TRP53) deficiency-mediated antiapoptosis escape after 5 Gy X irradiation still induces stem cell leukemia in C3H/He mice : comparison between whole-body assay and bone marrow transplantation (BMT) assay.2007

    • Author(s)
      Yoshida K、Hirabayashi Y、(4名省略)、Inoue T.
    • Journal Title

      Radiat Res 167

      Pages: 703-10

  • [Journal Article] Tumor suppressor function of aryl hydro- carbon receptor (AhR): early onsets of sponta- neous lymphoma and hepatoma、and resulting shortened life span observed in AhR deficient mice.2006

    • Author(s)
      Hirabayashi Y、Yoon BI、(4名省略)、Inoue T.
    • Journal Title

      Organohalogen Compounds 68

      Pages: 556-559

  • [Journal Article] Thioredoxin overexpression in mice、model of attenuation of oxidative stress、prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma.2006

    • Author(s)
      Li GX、Hirabayashi Y、Yoon BI、Kawasaki Y、Tsuboi I、(4名省略)、Inoue T.
    • Journal Title

      Exp Hematol 34

      Pages: 1687-97

  • [Journal Article] Caloric restriction prevents radiation-induced myeloid leukemia in C3H/HeMs mice and inversely increases incidence of tumor-free death: implications in changes in number of hemopoietic progenitor cells.2006

    • Author(s)
      Yoshida K、Hirabayashi Y、(2名省略)、Inoue T.
    • Journal Title

      Exp Hematol 34

      Pages: 274-83

  • [Journal Article] Meeting report : Validation of toxicogenomics-based test systems: ECVAM-ICCVAM/NICEATM considerations for regulatory use.2006

    • Author(s)
      Corvi R、(11名省略)、Inoue T、(10名省略)、Schechtman LM.
    • Journal Title

      Environ Health Perspect 114

      Pages: 420-9

  • [Journal Article] 新しい視点からみたトキシコロジー-発生・成長・老化-2006

    • Author(s)
      上達
    • Journal Title

      The Journal of Toxicological Sciences 31(5)

      Pages: 69-73

  • [Journal Article] 老化と生体異物2006

    • Author(s)
      平林容子、井上達
    • Journal Title

      基礎老化研究 30(4)

      Pages: 9-15

  • [Presentation] ベンゼンの造血障害発現機構 : 多環芳香族炭化水素受容体の関与と骨髄特異的異物代謝続報2008

    • Author(s)
      井上達、尹秉一、(3名省略)、平林容子
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-12
  • [Presentation] チオレドキシン(Trx)遺伝子改変(ノックアウト及び過剰発現)マウスにおける異物相互作用2008

    • Author(s)
      平林容子、尹秉一、(3名省略)、井上達
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-11
  • [Presentation] Y:Gompertzean expression of the life span: Toxicological ultimate risk for xenobiotic responses.2008

    • Author(s)
      Inoue T、Hirabayashi Y
    • Organizer
      The 45^<th> Congress of the European Societies of Toxicology
    • Place of Presentation
      Athens, Greece
    • Year and Date
      2008-10-06
  • [Presentation] Hirabayashi Y、Yoon BI、(4名省略)、Inoue T2008

    • Author(s)
      Hirabayashi Y、Yoon BI、(4名省略)、Inoue T
    • Organizer
      28^<th> International Symposium on Halogenated Environmental Organic Pollutants and POPs (Dioxin 2008)
    • Place of Presentation
      Birmingham, UK
    • Year and Date
      2008-08-19
  • [Presentation] Benzene-induced hematopoietic impairment is mediated by aryl hydrocarbon receptor (AhR) function compartmentalized in the bone marrow.2008

    • Author(s)
      Hirabayashi Y、Yoon BI、(4名省略)、Inoue T
    • Organizer
      The 37^<th> Annual Scientific Meeting
    • Place of Presentation
      Boston, MA
    • Year and Date
      2008-07-09
  • [Presentation] アリールハイドロカーボン受容体の生物学とトキシコロジー2008

    • Author(s)
      平林容子、李光勲、尹秉一、(4名省略)、井達
    • Organizer
      第35回日本トキシコロジー学会学術年会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-26
  • [Presentation] 一般口演「血液2」ベンゼン誘発白血病の分子機構 : チオレドキシン過剰発現によるROS消去と白血病の抑制2008

    • Author(s)
      平林容子、李光勲、尹秉一、(3名省略)、井上達
    • Organizer
      第97回日本病理学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2008-05-16
  • [Presentation] Benzene-inhalation enhanced the incidence of hematopoietic neoplasms in p53-deficient mice with respect to strain- differences between C57BL/6 and C3H/He.2008

    • Author(s)
      Hirabayashi Y、Yoon BI、Tsuboi I、(2名省略)、Inoue T
    • Organizer
      Society of Toxicology 47^<th> Annual Meeting & ToxExpo
    • Place of Presentation
      Seattle WA
    • Year and Date
      2008-03-16
  • [Presentation] Role of Cx32 in steady-state hematopoiesis and leukemogenesis : study in the Cx32-knockout mice.2008

    • Author(s)
      Hirabayashi Y、Yoon BI、Tsuboi I、(2名省略)、Inoue T
    • Organizer
      Society of Toxicology 47^<th> Annual Meeting & ToxExpo
    • Place of Presentation
      Seattle,WA
    • Year and Date
      2008-03-16
  • [Presentation] ゴンパーツ函数を指標とした生体異物相互作用の加齢に及ぼす影響2007

    • Author(s)
      井上達、平林容子
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-14
  • [Presentation] 基調講演海外における化学物質の内分泌かく乱作用に関する取り組みWHO/IPCSの取り組み2007

    • Author(s)
      井上達
    • Organizer
      化学物質の環境リスクに関する国際シンポジウム化学物質の内分泌かく乱作用について~10年間のあゆみ~
    • Place of Presentation
      大宮
    • Year and Date
      2007-12-09
  • [Presentation] Attenuation of oxidative stress in the Trx-overexpression mice : Study on benzene induced hemopoietic malignancies.2007

    • Author(s)
      Inoue T
    • Organizer
      The 4^<th> Meeting of International REDOX Network
    • Place of Presentation
      Jeju Island, Korea
    • Year and Date
      2007-11-02
  • [Presentation] ベンゼンの造血障害発現機構 : 多環芳香族炭化水素受容体の関与と骨髄特異的異物代謝の関与の役割について2007

    • Author(s)
      井上達、尹秉一、(3名省略)、平林容子
    • Organizer
      第69回日本血液学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-11
  • [Presentation] Hemopoietic progenitors express aryl hydro- carbon receptors that suppress the cell cycle, thereby restoring their stemness.2007

    • Author(s)
      平林容子、尹秉一、(5名省略)、井上達
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
  • [Presentation] AhR, a suppressor gene: mice with low AhR or KO exhibit a shortened lifespan with early onset of spontaneous neoplasms.2007

    • Author(s)
      井上達、尹秉一、(5名省略)、平林容子
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
  • [Presentation] Aryl hydrocarbon receptor suppresses spontaneous neoplasms and extends life span: possible mechanism implied by hematopoietic stem cell kinetics.2007

    • Author(s)
      Hirabayashi Y、Yoon BI、(3名省略)、Inoue T
    • Organizer
      27th International Symposium on Halogeneated Environmental Organic Pollutants and POPs (Dioxin 2007)
    • URL

      日本基礎老化学会第30回大会

    • Place of Presentation
      Tokyo
    • Year and Date
      2007-09-04
  • [Presentation] A new toxicological biomarker, connexin 32, in the hematopoietic stem cells: the deficiency induced a prolongation of chemical damage and an increased incidence of leukemogenesis.2007

    • Author(s)
      Hirabayashi Y、Yoon BI、Tsuboi I、(5名省略)、Inoue T
    • Organizer
      International Congress of Toxicology XI
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2007-07-18
  • [Presentation] 話題提供「老化と環境化学物質生体応答」2007

    • Author(s)
      井上達、平林容子
    • Organizer
      日本基礎老化学会第30回大会
    • Place of Presentation
      札幌
    • Year and Date
      2007-06-22
  • [Presentation] 一般口演「腫瘍3」芳香族炭化水素受容体(AhR)の細胞周期抑制を介した腫瘍サプレッサー機能2007

    • Author(s)
      平林容子、(4名省略)、井上達
    • Organizer
      第96回日本病理学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-03-14
  • [Presentation] アリールハイドロカーボン受容体 : 癌抑制遺伝子モデル2006

    • Author(s)
      平林容子、(5名省略)、井上達
    • Organizer
      第23回日本疾患モデル学会
    • Place of Presentation
      伊香保
    • Year and Date
      2006-11-30
  • [Presentation] Effect of endocrine disruptors on health : possible underlying mechanistic background of low-dose and synergistic actions.2006

    • Author(s)
      Inoue T
    • Organizer
      Weybridge+10 Workshop Impacts of Endocrine Disrupters
    • Place of Presentation
      Helsinki, Finland
    • Year and Date
      2006-11-10
  • [Presentation] Xenobiotic response gene, aryl hydrocarbon receptor (AhR), plays a tumor suppressive function : an early onset and higher incidence of spontaneous tumori-/leukemogenicity and a consequent shortened lifespan in the AhR knockout mouse.2006

    • Author(s)
      Hirabayashi Y、(5名省略)、Inoue T
    • Organizer
      An AACR Special Conference in Cancer Research "Mouse Models of Cancer"
    • Place of Presentation
      Boston, MA
    • Year and Date
      2006-10-26
  • [Presentation] Tumor suppressor function of aryl hydrocarbon receptor (AhR) : early onsets of spontaneous lymphoma and hepatoma, and resulting shortened life span observed in AhR deficient mice.2006

    • Author(s)
      Hirabayashi Y、Yoon BI、(4名省略)、Inoue T
    • Organizer
      26^<th> International Symposium on Halogeneated Environmental Organic Pollutants and POPs (Dioxin 2006)
    • Place of Presentation
      Oslo. Norway
    • Year and Date
      2006-08-22
  • [Presentation] ベンゼンの毒性は、骨髄特異的異物代謝によって引き起こされる2006

    • Author(s)
      平林容子、尹秉一、(4名省略)、井上達
    • Organizer
      第33回日本トキシコロジー学会学術年会
    • Place of Presentation
      名古屋
    • Year and Date
      2006-07-05
  • [Presentation] 教育講演EL2 新しい視点から見たトキシコロジー : 発生・成長・老化2006

    • Author(s)
      井上達
    • Organizer
      第33回日本トキシコロジー学会学術年会
    • Place of Presentation
      名古屋
    • Year and Date
      2006-07-04
  • [Presentation] Possible stem cell-specific xenobiotic metabolism in the bone marrow.2006

    • Author(s)
      Hirabayashi Y, Yoon BI、(4名省略)、Inoue T
    • Organizer
      International Society of Stem Cell Research 4^<th> ISSCR Annual Meeting
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      2006-06-30
  • [Presentation] Global Gene-Expression Profilings of Steady-State Mice Carrying A Graded Dosage of Trx-Gene Elucidate Major Principal Gene-Component for the ROS-removal and for Trx-Dependent Anti-Oxidative Stress.2006

    • Author(s)
      Inoue T, Yoon BI、(3名省略)、Hirabayashi Y
    • Organizer
      20^<th> IUBMB International Congress of Biochemistry and Molecular Biology
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-23
  • [Presentation] Summary and Future Directions "Regulation of hematopoiesis".2006

    • Author(s)
      Inoue T
    • Organizer
      Pathophysio- logy & Molecular Biology of Hematopoiesis, Malignancy & Radiation Response "Internatio- nal Symposium in Memory of Eugene P. Cronkite, M.D."
    • Place of Presentation
      Upton, NY
    • Year and Date
      2006-05-12
  • [Presentation] 一般口演「造血器・リンパ節・脾臓6」アリールハイドロカーボン受容体の造血細胞での特異な発現とベンゼンの造血障害における役割2006

    • Author(s)
      平林容子、尹秉一、(4名省略)、井上達
    • Organizer
      第95回日本病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      2006-04-29
  • [Presentation] AhR mediated hematotoxicity is induced at the site of bone marrow where consequent CYP2E1-derived benzene metabolites locally induce their toxicity.2006

    • Author(s)
      Hirabayashi Y、Yoon BI、(4名省略)、Inoue T
    • Organizer
      Society of Toxicology 45^<th> Annual Meeting & ToxExpo
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2006-03-06
  • [Book] Principles of data-mining in toxicogenomics. In Toxicogenomics: A Powerful Tool for Toxicity Assessment (S. C. Sahu, Ed.)2007

    • Author(s)
      Hirabayashi Y、Inoue T.
    • Total Pages
      57-84
    • Publisher
      John Wiley & Sons, Ltd.
  • [Book] 新しい視点からみたトキシコロジー-発生・成長・老化-. In トキシコロジーの到達点と新しい展望-多様性科学としてのトキシコロジー-(堀井郁夫編),

    • Author(s)
      井上達
    • Publisher
      第33回日本トキシコロジー学会学術年会
  • [Patent(Industrial Property Rights)] 発がんプロモーター作用の測定法2008

    • Inventor(s)
      佐井君江、菅野 純、井上達
    • Industrial Property Rights Holder
      国立医薬品食品衛生研究所所長
    • Industrial Property Number
      特許第4171796
    • Acquisition Date
      2008-08-22

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Published: 2010-06-10   Modified: 2016-04-21  

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