• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

タンパク損傷を起源とする放射線発がん経路

Research Project

Project/Area Number 19651020
Research Category

Grant-in-Aid for Exploratory Research

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

Principal Investigator

渡邉 正己  Kyoto University, 原子炉実験所, 教授 (20111768)

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: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2007: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywords放射線発がん / 染色体異数化 / 中心体構造異常 / ミトコンドリア / 染色体構造異常 / 酸化ラジカル / 非DNA損傷 / タンパク損傷 / 三倍体 / 四倍体 / 中心体
Research Abstract

本研究は、放射線発がんが、"DNA損傷→突然変異→細胞がん化"とする古典的な経路(突然変異説)ではなく、"タンパク損傷→染色体異数化→細胞がん化"とする経路が主経路であるとする我々の仮説の是非を検証することを目的として計画した。特に、本提案課題では、放射線発がんの第一標的として、染色体分配装置の安定化に関係するタンパク質成分のうち、テロメア、セントロメアおよび中心体の3種に的を絞り、それらの構造および機能異常が細胞がん化の直接の原因であるかどうかを調べた。
本研究には、放射線による細胞がん化、突然変異、および染色体解析を定量的に行うことのできるシリアンハムスター胎児由来(SHE)細胞、および、結果のヒトへの応用を念頭においてヒト由来培養(HE)細胞を併用した。その結果、(1)放射線照射後、悪性形態変換頻度を判定するコロニー形成までの時期のどの時期に染色体の数的異常が現れてくるかを染色体のマルチカラーFISH法等を使って詳細に検討し、染色体異数化が放射線発がんの起源であることが判った。(2)染色体異数化は、中心体の構造・機能異常が原因で生ずることが判った。(3)中心体の構造異常は、放射線によって直接誘導されるのではなく、ミトコンドリアにおける電子伝達経路の恒常性崩壊が原因となって上昇する細胞内酸化ラジカルが原因となっていることが判った。(4)二動原体染色体は、極めて低率であるが染色体構造異常の原因となるが、染色体異数化の原因とはならないことが判った。等の成果が得られた。これらの結果は、発がん経路にDNA損傷を起源としない経路が存在し、その経路が発がんの主計路であることを示唆している。

Report

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

    (18 results)

All 2009 2008 2007 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Intervention of oxygen-control ability to radiation sensitivity, cell aging and cell transformation.2009

    • Author(s)
      Yoshii H, Watanabe M
    • Journal Title

      J Radiat Res (Tokyo) 50

      Pages: 127-137

    • NAID

      10025911412

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different involvement of radical species in irradiated and bystander cells.2009

    • Author(s)
      Harada T, Kashino G, Suzuki K, Matsuda N, Kodama S, Watanabe M
    • Journal Title

      Int J Radiat Biol 379

      Pages: 809-814

    • 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, Maruo A, Suzuki K, Watanabe M
    • Journal Title

      Radiat Res 171

      Pages: 198-203

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylated H2AX foci in tumor cells have no correlation with their radiation sensitivities.2009

    • Author(s)
      Yoshikawa T, Kashino G, Ono K, Watanabe M
    • Journal Title

      J Radiat Res (Tokyo) 50

      Pages: 151-160

    • NAID

      10025911507

    • 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)
      Hamamoto T, Suzuki K, Yamauchi M, Kodama S, Sasaki H, Watanabe M
    • Journal Title

      Int J Hyperthermia 24

      Pages: 415-425

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Introduction of a normal human chromosome 8 corrects abnormal phenotypes of Werner syndrome cells immortalized by exppressing an hTERT gene.2009

    • Author(s)
      Ariyoshi K, Suzuki K, Goto M, Oshimura M, Ishizaki K, Watanabe M, Kodama S
    • Journal Title

      J Radiat Res (Tokyo) (in press)

    • 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)
      Kashino G Kondoh T, Watanabe, M, ほか13名
    • Journal Title

      Intern J Radiat Oncol Biol Phys (in press)

    • 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.2009

    • Author(s)
      Yamauchi M, Oka Y, Kodama S, Watanabe M, Suzuki K, ほか5名
    • Journal Title

      DNA Repair (Amst) 7

      Pages: 405-417

    • NAID

      120006983929

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation and characterization of cells that can be conditionally depleted of mitochondrial SOD2.2008

    • Author(s)
      Takada S, Inoue E, Tano K, Watanabe M, Enomoto T, ほか6名
    • Journal Title

      Biochem Biophys Res Commun 379

      Pages: 233-238

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased chromosome instability and accumulation of DNA double-strand breaks in Werner syndrome Cells.2007

    • Author(s)
      Ariyoshi K, Suzuki K, Goto M, Watanabe M, Kodama S
    • Journal Title

      J. Radiat. Res. (Tokyo) 48

      Pages: 219-231

    • NAID

      110006278197

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transmission of Genomic Instability from a Single Irradiated Human Chromosome to the Progeny of Unirradiated Cells.2007

    • Author(s)
      ukaida N, Kodama S, Suzuki K, Oshimura M, Watanabe M
    • Journal Title

      Radat Res 167

      Pages: 675-681

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The higher lethality of UVB radiation to cultured human cells is associated with the specific activation of a DNA damage-independent signaling pathway.2007

    • Author(s)
      Horikawa-Miura M, Yoshida M, Okumura Y, Mori T, Watanabe M, Matsuda N
    • Journal Title

      Radiat Res 167

      Pages: 655-662

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] The main route of radiation-induced carcinogenesis is the same as that of natural carcinogenesis.2009

    • Author(s)
      Watanabe M, Yoshii H, Watanabe K
    • Organizer
      The 54th Annual Meeting of the Radiation Research
    • Place of Presentation
      Boston, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] 特別講演 ; 放射線発がんの新しい機構-DNA損傷を起源としない経路の2008

    • Author(s)
      渡邉正己
    • Organizer
      第14回放射線癌治療増感研究会(招待講演)
    • Place of Presentation
      鈴鹿
    • Related Report
      2008 Annual Research Report
  • [Presentation] 細胞がん化には倍数化より異数化が深く関与する2008

    • Author(s)
      渡邉正己, 吉居華子
    • 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] ミトコンドリア機能と細胞がん化2008

    • Author(s)
      渡邉正己, 吉居華子
    • Organizer
      第8回日本ミトコンドリア学会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] Main route of radiation-carcinogenesis is DNA damage-independent pathways2007

    • Author(s)
      Watanabe M, Yoshii H, Watanabe K, Suzuki K, Kodama S, Kumagai J
    • Organizer
      International congress of Radiation Research
    • Place of Presentation
      San Fransisco
    • Year and Date
      2007-08-24
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.rri.kyoto-u.ac.jp/rb-rri/

    • Related Report
      2008 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi