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放射線被ばくによるヒト体性幹細胞におけるゲノム不安定性の研究

Research Project

Project/Area Number 19651023
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Risk sciences of radiation/Chemicals
Research InstitutionNagasaki University

Principal Investigator

朝長 万左男  Nagasaki University, 大学院・医歯薬学総合研究科, 教授 (40100854)

Co-Investigator(Kenkyū-buntansha) 鈴木 啓司  長崎大学, 大学院・医歯薬学総合研究科, 准教授 (00196809)
長井 一浩  長崎大学, 医学部・歯学部附属病院, 講師 (30304942)
岩永 正子  長崎大学, 大学院・医歯薬学総合研究院, 助教 (00372772)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2008: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2007: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywords放射線被ばく / 幹細胞 / 放射線誘発遅延性ゲノム不安定状態 / 発がん機構
Research Abstract

1.被ばく者試料サンプリング
計画書に策定した手順に則り、原子爆弾被ばく者検診センターおよび長崎大学病院血液内科受診のプロセスから、現時点までに12例の原子爆弾被ばく者の骨髄試料をサンプリングしている。今年度は、サンプリングを効率よく進めるために、関連協力医療機関の血液内科においても検体採取を行うシステムを構築した。更に、被ばく者コホートを基盤とした組織バンキング・システムの今年度稼働開始に伴い、後述する骨髄血以外のサンプリングを開始することによる解析対象サンプル数の増加およびバンキング・システムとリンクした臨床情報等豊富なデータベースを用いた分析を可能とする体制を確立した。
2.幹細胞のゲノム不安定性解析
昨年度に引き続き、CD34、ABCG2、CD133およびCD271等各種マーカー蛋白の発現を指標とした幹細胞画分におけるリン酸化ヒストンH2AXフォーカス形成の免疫学的in situ検出法を用いて、データを集積中である。
更に今年度は、本研究で立てた「仮説」を検証する上で最重要であるところのクローンレベルでの解析を行うべく、単一幹細胞を分取後にex vivo増幅を行ったうえで上記ゲノム不安定性の解析に供する系を確立しており、既に対象検体に対してデータの蓄積を重ねている。この方法では、骨髄検体以外にも末梢血中のCD34陽性細胞等の稀少細胞であっても分取と増幅が可能であることから、現在多種のサンプル中の幹細胞集団を対象にしたクローン解析を展開している。

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (23 results)

All 2009 2008 2007

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (12 results) Book (1 results)

  • [Journal Article] Relationship Between Monoclonal Gammopathy of Undetermined Significance and Radiation Exposure in Nagasaki Atomic Bomb Survivors.2009

    • Author(s)
      Iwanaga M., et al.
    • Journal Title

      Blood 113

      Pages: 1639-1650

    • NAID

      120006982803

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The contribution of radiation-induced large deletion of the genome to chromosomal instability.2009

    • Author(s)
      Toyokuni H., et al.
    • Journal Title

      Radiat Res. 171

      Pages: 198-203

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutation analysis of RAP1 gene in papillary thyroid carcinomas.2009

    • Author(s)
      Matsuse M., et al.
    • Journal Title

      Endocrinal J. 56

      Pages: 161-164

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reciprocal paracrine interactions between normal human epithelial and mesenchymal cells protect cellular DNA from radiation-induced damage.2008

    • Author(s)
      Nakazawa Y., et al.
    • Journal Title

      Int. J Radiat Oncol Biol Phys. 71

      Pages: 567-577

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different involvement of radical species in irradiated and bystander cells.2008

    • Author(s)
      Harada T., et al.
    • Journal Title

      Int J Radiat Biol. 84

      Pages: 809-814

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alteration of p53-binding protein 1 expression during skin carcinogenesis : association with genomic instability.2008

    • Author(s)
      Naruke Y., et al.
    • Journal Title

      Cancer Sci. 99

      Pages: 946-951

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of myeloperoxidase enhances the chemosensitivity of 1 eukemia cells through the generation of reactive oxygen species and the nitration of protein.2008

    • Author(s)
      Sawayama Y., et al.
    • Journal Title

      Leukemia 22

      Pages: 956-964

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Growth of persistent foci of DNA damage checkpoint factors is essential for amplification of G1 checkpoint signaling.2008

    • Author(s)
      Yamauchi M., et. al.
    • Journal Title

      DNA Repair 7

      Pages: 405-417

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Foci formation of P53-binding protein 1 in thyroid tumors: activation of genomic instability during thyroid carcinogenesis.2008

    • Author(s)
      Nakashima M., et. al.
    • Journal Title

      Int J Cancer. 122

      Pages: 1082-1088

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence of monoclonal gammopathy of undetermined significance: study of 52,802 persons in Nagasaki City, Japan.2007

    • Author(s)
      Iwanaga M., et. al.
    • Journal Title

      Mayo Clin Proc. 82

      Pages: 1474-1479

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Higher-order chromatin structure and radiation-induced genomic instability.2008

    • Author(s)
      Suzuki K., et al.
    • Organizer
      International Conference on Radiation Biology
    • Place of Presentation
      Jaipur, India
    • Related Report
      2008 Annual Research Report
  • [Presentation] Higher-order chromatin structure and non-targeted effects.2008

    • Author(s)
      Suzuki K., et al.
    • Organizer
      Columbia University International Symposium in Honor of Professor Eric J. Hall
    • Place of Presentation
      New York, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Amplification of ATM-dependent checkpoint signals coupled with NHEJ repair.2008

    • Author(s)
      Suzuki K., et al.
    • Organizer
      Ataxia-Telangiectasia Workshop 2008
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] Growth of persistent foci of DNA damage checkpoint factors is essential for amplification of G1 checkpoint signaling.2008

    • Author(s)
      Yamauchi M., et al.
    • Organizer
      Ataxia-Telangiectasia Workshop 2008
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] Relationship between persistent formation of phosphorylated ATM/53BP1 foci and radiation induced permanent cell cycle arrest examined by single-cell based assay.2008

    • Author(s)
      Oka Y., et al.
    • Organizer
      Ataxia-Telangiectasia Workshop 2008
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] ATM regulates IGF-1-secretory clusterin induction pathway during replicative senescence.2008

    • Author(s)
      Suzuki M., et al.
    • Organizer
      Ataxia-Telangiectasia Workshop 2008
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] 放射線誘発ゲノム欠失によるクロマチン高次構造変化と不安定性.2008

    • Author(s)
      鈴木啓司, 他.
    • Organizer
      第31回日本分子生物学会大会
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] DNA損傷チェックポイント増幅と相同組換え修復との共役.2008

    • Author(s)
      鈴木啓司, 他.
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] Living Cell ImagingによるDNA損傷応答のダイナミクス解析.2008

    • Author(s)
      鈴木啓司, 他.
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州
    • Related Report
      2008 Annual Research Report
  • [Presentation] DNA二重鎖切断誘発クロマチン高次構造異常によるATM分子活性化機構.2008

    • Author(s)
      鈴木啓司, 他.
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州
    • Related Report
      2008 Annual Research Report
  • [Presentation] 放射線照射正常ヒト細胞における遅延的ストレスの増加へのミトコンドリアの関与.2008

    • Author(s)
      小橋川新子, 他.
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州
    • Related Report
      2008 Annual Research Report
  • [Presentation] 放射線照射後のG2/Mチェックポイント誘導に関与するDNA損傷シグナルの定量的解析.2008

    • Author(s)
      石川 彩, 他.
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州
    • Related Report
      2008 Annual Research Report
  • [Book] Leukemia, Lymphoma, and Multiple Myeloma Incidence in the LSS Cohort - 1950-2001. Radiation Health Risk Sciences : Proceedings of the First International Symposium of the Nagasaki University Global COE Program.2008

    • Author(s)
      Wan-Ling Hsu., et al.
    • Publisher
      Springer-Verlag
    • Related Report
      2008 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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