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2005 Fiscal Year Final Research Report Summary

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
Keywordsmismatch repair / mutation / biological significance / mouse / lacZ
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.

  • Research Products

    (7 results)

All 2006 2005 2004 2003

All Journal Article (7 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

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

URL: 

Published: 2007-12-13  

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