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Analysis of biological significance of elevated mutation

Research Project

Project/Area Number 15310031
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionTohoku University

Principal Investigator

ONO Tetsuya  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00107509)

Co-Investigator(Kenkyū-buntansha) IKEHATA Hironobu  Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (90250737)
UEHARA Yoshihiko  Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (30223499)
NAKAMURA Nori  Radiation Effects Research Foundation, Department of Genetics, Chief Scientist, 遺伝学部, 部長 (00010116)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2005: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥7,800,000 (Direct Cost: ¥7,800,000)
Keywordsmismatch repair / mutation / biological significance / mouse / lacZ / 染色体
Research Abstract

Although alterations of genome are supposed to be one of the major causes of cancer and senescence, the details of the process are not know yet. The knock-out mice in the mismatch repair genes showed an elevation of spontaneous mutation and a high incidence of cancer, suggesting a close relationship between genomic alteration and cancer induction. The mice, however, revealed high levels of mutation in many tissues and most of the tissues did not show cancer nor accelerated senescence phenotype. In an attempt to understand a relationship between mutation and cancer or senescence, we analyzed the details of the mutation and tissue alteration in the mismatch repair deficient mice. Both Mlh1 and Msh2-deficient mice showed high levels of mutation in embryo stage, but no appreciable alteration was found in tissue morphology, development or growth. The level of apoptosis was not affected either. We also examined if the cells suffering from radiation-induced chromosomal abnormality could be eliminated from body. The analysis using wild-type mice showed that the frequencies of chromosome abnormality in lymphocytes analyzed 2 to 4 months after irradiation were low when the irradiation was done during late embryo and early neonatal stages but high when irradiated at later age. It suggests a presence of cell elimination system against cells harboring chromosomal abnormality. These studies suggest that the relationship between the elevation of genomic alteration and cancer or senescence is not simple but many biological factors must be intervening between them.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (22 results)

All 2006 2005 2004 2003 Other

All Journal Article (16 results) Publications (6 results)

  • [Journal Article] The maintenance of genome integrity is tissue-specific.2006

    • Author(s)
      T.Ono
    • Journal Title

      Genes and Environment 28

      Pages: 16-22

    • NAID

      110004740318

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mutations spectrum in UVB-exposed skin epidermis of a mildlyaffected Xpg-deficient mouse.2006

    • Author(s)
      F.Wang
    • Journal Title

      Environmental and Molecular Mutagenesis 47・2

      Pages: 107-116

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hypermethylation of CpGs in the promoter of the COL1A1 gene in the aged periodontal ligament.2006

    • Author(s)
      T.Ohi
    • Journal Title

      Journal of Dental Research 85・3

      Pages: 245-250

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The maintenance of genome integrity is tissue-specific.2006

    • Author(s)
      T.Ono
    • Journal Title

      Genes and Environment (in press)

    • NAID

      110004740318

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A hypothesis : radiation-related leukemia is mainly attributable to the small number of people who carry pre-existing clonally expanded preleukemic cells.2005

    • Author(s)
      N.Nakamura
    • Journal Title

      Radiation Research 163

      Pages: 258-265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Disappearance of nucleosome positioning in mitotic chromatin in vivo.2005

    • Author(s)
      J.Komura
    • Journal Title

      Journal of Biological Chemistry 280・15

      Pages: 14530-14535

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Disappearance of nucleosome positioning in mitotic chromatin in vivo.2005

    • Author(s)
      Jun-ichiro Komura
    • Journal Title

      Journal of Biological Chemistry (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A hypothesis : radiation-related leukemia is mainly attributable to the small number of people who carry pre-existing clonally expanded preleukemic cells.2005

    • Author(s)
      Nori Nakamura
    • Journal Title

      Radiation Research 163・3

      Pages: 258-265

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Spontaneous mutations in digestive tract of old mice show tissue-specific patterns of genomic instability.2004

    • Author(s)
      T.Ono
    • Journal Title

      Cancer Research 64

      Pages: 6919-6923

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Human fetuses do not register chromosome damage inflicted by radiation exposure in lymphoid precursor cells except for a small but significant effect at low doses.2004

    • Author(s)
      K.Ohtaki
    • Journal Title

      Radiation Research 161

      Pages: 373-379

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Human fetuses do not register chromosome damage inflicted by radiation exposure in lymphoid precursor cells except for a small but significant effect at low doses.2004

    • Author(s)
      K, Ohtaki
    • Journal Title

      Radiation Research 161

      Pages: 373-379

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Spontaneous mutations in digestive tract of old mice show tissue-specific patterns of genomic instability.2004

    • Author(s)
      Tetsuya Ono
    • Journal Title

      Cancer Research 64・19

      Pages: 6919-6923

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mutation spectrum in sunlight-exposed mouse skin epidermis : small but appreciable contribution of oxidative stress-mediated mutagenesis.2004

    • Author(s)
      Hironobu Ikehata
    • Journal Title

      Mutation Research 556・1-2

      Pages: 11-24

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human fetuses do not register chromosome damage inflicted by radiation exposure in lymphoid precursor cells except for a small but significant effect at low doses.2004

    • Author(s)
      K.Ohtaki
    • Journal Title

      Radiation Research 161・4

      Pages: 373-379

    • Related Report
      2004 Annual Research Report
  • [Journal Article] UVA induces C->T transitions at methyl-CpG-associated dipyrimidine sites in mouse skin epidermis more frequently than UVB.2003

    • Author(s)
      H.Ikehata
    • Journal Title

      Mutagenesis 18

      Pages: 511-519

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular nature of mutations induced by irradiation with repeated low doses of X-rays in spleen, liver, brains and testis of lacZ-transgenic mice.2003

    • Author(s)
      T.Ono
    • Journal Title

      International Journal of Radiation Biology 79

      Pages: 635-641

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Hironobu Ikehata: "Analysis of mutations spectra in UVB-exposed mouse skin epidermis and dermis : Frequent occurrence of C->T transition at methylated CpG-associated dipyrimidine sites"Environmental and Molecular Mutagenesis. 41(3). 280-292 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuki Nagata: "X-ray-induced mutations in Escherichia coli K-12 strains with altered DNA polymerase I activities"Mutation Research. 528. 93-103 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tetsuya Ono: "Molecular nature of mutations induced by irradiation with repeated low doses of X-rays in spleen, liver, brain and testis of lacZ-transgenic mice"International Journal of Radiation Biology. 79(8). 635-641 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hironobu Ikehata: "UVA induces C->T transitions at methyl-CpG-associated dipyrimidine sites in mouse skin epidermis more frequently than UVB"Mutagenesis. 18(6). 511-519 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Minako Nakano: "Estimating the number of hematopoietic or lymphoid stem cells giving rise to clonal chromosome aberrations in blood T lymphocytes"Radiation Research. 161(3). 273-281 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nori Nakamura: "Prediction of clonal chromosome, aberration frequency in human blood lymphocytes"Radiation Research. 161(3). 282-289 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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