Mechanism of functional impairment of the hematopoietic stem cell niches by oxidative stress in the site of xenobiotic interrelationship

2010 Fiscal Year Self-evaluation Report

• Project/Area Number: 20590388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National Institute of Health Sciences
• Principal Investigator: HIRABAYASHI Yoko National Institute of Health Sciences, 安全性生物試験研究センター毒性部, 室長 (30291115)
• Project Period (FY): 2008 – 2011
• Keywords: 造血幹細胞 / 幹細胞ニッチ / 生体異物相互作用 / 細胞周期 / 酸化的ストレス

Research Abstract

本研究は、(1)低酸素状態で維持される幹細胞の静止期[dormancy]における維持機構と、細胞周期内における自己複製の調節機構、(2)造血幹細胞の細胞周期静止機構の成立とこれにかかる新生児期の造血動態変化の分子機構、(3)造血幹細胞特異的細胞周期測定法と定常状態[steady state]における細胞周期静止分画の酸化的ストレス蓄積過程としての加齢・老化に伴う変化、の3点から構成され、これら活性酸素の関与した造血の調節機構を、生理機構と病的障害機構の両面から追求した。

Research Products

• [Journal Article] Benzeneinduced bone-marrow toxicity : a hematopoietic stem-cell-specific, aryl hydrocarbon receptor-mediated adverse effect. (2010)
  • Author(s): Hirabayashi Y, Inoue T.
  • Journal Title: Chem Biol Interact 184(1-2) Pages: 252-258
  • Peer Reviewed
• [Journal Article] Regeneration capability of Lin^-/c-Kit^+/Sca-1^+ cells with or without radiation exposure for repopulation of peripheral blood in lethally irradiated mice monitored using Ly5.1 isotype on days 35, 90, and 270 after transplantation. (2010)
  • Author(s): Otsuka K, Hirabayashi Y, Tsuboi I, Inoue T.
  • Journal Title: Exp Hematol 38(5) Pages: 417-425
  • Peer Reviewed
• [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, Kitada K, Igarashi K, Kodama Y, Kanno J, Yoshida, K, Dainiak, N., Inoue T.
  • Journal Title: Exp Hematol 37(2) Pages: 195-205
  • Peer Reviewed
• [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(4) Pages: 521-535
  • Peer Reviewed
• [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, Li GX, Fujii-Kuriyama Y, Kaneko T, Kanno J, Inoue T.
  • Journal Title: Chemosphere 73(1Suppl) Pages: S290-294
  • Peer Reviewed
• [Presentation] Radiation and senescence : Deceleration of cell-cycle in primitive hemopoietic progenitors (CFUS13) was only significant parameter during aging, which was reactively accelerated after 2Gy whole-body irradiation. (2011)
  • Author(s): Hirabayashi Y, Tsuboi I, Sekita K, Kanno J, Kusunoki Y, Inoue T
  • Organizer: Society of Toxicology 50^<th> Annual Meeting & ToxExpo
  • Place of Presentation: Washington DC, USA.
  • Year and Date: 2011-03-08
• [Presentation] Strain differences of the effect of benzene exposure : microarray study of the bone marrow in C57BL/6 and C3H/He mice. (2010)
  • Author(s): Hirabayashi Y, Yoon BI, Igarashi K, Kodama Y, Sekita K, Kaneko T, Kanno J, Inoue T
  • Organizer: IUTOX 2010-XII International Congress of Toxicology
  • Place of Presentation: Barcelona, Spain.
  • Year and Date: 2010-07-21
• [Presentation] Thioredoxin-overexpression mice prevent benzene-induced lymphoma/leukemias : Experimental model for possible beneficial role in anti-oxidative stress by broccoli (Sulforaphan). (2009)
  • Author(s): Inoue T, Hirabayashi Y
  • Organizer: Asia Pacific Symposium on Food Safety 2009
  • Place of Presentation: Seoul, Korea.
  • Year and Date: 2009-11-13
• [Presentation] Benzene-induced toxicity is based on the AhR-mediated hematopoietic stem cells (2009)
  • Author(s): Hirabayashi Y
  • Organizer: Benzene 2009 : Health Effects and Mechanisms of Bone Marrow Toxicity, Implication for t-AML and the Mode of Action Framework.
  • Place of Presentation: Munich, Germany.
  • Year and Date: 2009-09-10
• [Presentation] Connexin 32 maintains quiescent hematopoietic progenitor cells in Lin^-/c-kit^+/Sca1^+ fraction : Analysis of the cell cycle. (2008)
  • Author(s): Hirabayashi Y, Yoon BI, Tsuboi I, Ott T, Trosko JE, Inoue T
  • Organizer: 6^<th> ISSCR Annual Meeting
  • Place of Presentation: Cairns, Australia.
  • Year and Date: 2008-06-14
• [Book] Handbook of Systems Toxicology, Vol.1(Casciano DA, Sahu SC, eds)(Commonality and Stochasticity in Systems Toxicology.) (2011)
  • Author(s): Hirabayashi Y, Inoue T.
  • Total Pages: 432-460
  • Publisher: Hoboken, NJ John Wiley & Sons, Ltd.
• [Book] Toxicogenomics : A Powerful Tool for Toxicity Assessment (Sahu SC, ed)(Principles of data-mining in toxicogenomics.) (2008)
  • Author(s): Hirabayashi Y, Inoue T.
  • Total Pages: 57-84
  • Publisher: Hoboken, NJ John Wiley & Sons, Ltd.