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2006 Fiscal Year Final Research Report Summary

Establishment of a sensitive assay system for detecting mutations induced by oxidative DNA damage

Research Project

Project/Area Number 16310043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionKYUSHU UNIVERCITY

Principal Investigator

TSUZUKI Teruhisa  Kyushu University, Faculty of Medical Sciences, Department of Medical Physics and Radiation Biology, Professor, 大学院医学研究院, 教授 (40155429)

Co-Investigator(Kenkyū-buntansha) NAKATSU Yoshimichi  Kyushu University, Faculty of Medical Sciences, Department of Medical Physics and Radiation Biology, Associate Professor, 大学院医学研究院, 助教授 (00207820)
HAYAKAWA Hiroshi  Fukuoka Dental College, Department of Biochemistry, Professor, 歯学部, 教授 (70150422)
Project Period (FY) 2004 – 2006
Keywordsgene / nucleic acids / environment / genome / radiation / mutation / mutagenesis / oxidative stress / reactive oxygen species
Research Abstract

Oxygen radicals are produced through normal cellular metabolism, and formation of such radicals is enhanced further by ionizing radiation and by various chemicals. The oxygen radicals attack nucleic acids and generate various modified bases in DNA. Among them, 8-oxoguanine (8-oxoG) is the most abundant, and seems to play a critical role in mutagenesis as well as carcinogenesis and aging. 8-OxoG can pair with both cytosine and adenine during DNA synthesis, and as a result, G : C to T : A transversions are induced. Oxidation of guanine also occurs in the cellular nucleotide pool. 8-Oxo-dGTP, when formed, is a potent mutagenic substrate for DNA synthesis ; it is equally incorporated opposite both adenine and cytosine in DNA, resulting in both A : T to C : G and G : C to T : A transversions. In order to establish a sensitive assay system for detecting mutagenesis caused by oxidative DNA damage, we used the rpsL transgene as a reporter for the mutation assay, a suitable system for identifying a spectrum of base substitutions and single-base frameshifts. Using the resulting DNA repair-deficient mice with the rpsL transgene (rpsL hemizygotes), we examined oxidative stress-induced mutations occurring in the tissues of different DNA repair-deficient mouse lines. The frequency of G : C to T : A transversions was significantly increased both in Ogg1^<-/-> and Mutyh^<-/-> mice when administered with KBrO_3 in drinking water. We observed an increased incidence of G : C to A : T transitions in Ogg1^<-/-> mice after exposure to low dose X-ray irradiation (4 Gy). We further detected a characteristic spectra of A : T to G : C transitions in the spleens of X-ray-irradiated Mth1^<-/-> mice. In this study, we have shown a characteristic difference in the mutational spectra of wild-type mice and several DNA repair-deficient mice, such as Mth1,Ogg1,and Mutyh.
We also examined the interaction between mammalian enzymes and oxidatively damaged ribonucleotides/RNA.

  • Research Products

    (24 results)

All 2007 2006 2005 2004 Other

All Journal Article (23 results) Book (1 results)

  • [Journal Article] MUTYH-null mice are susceptible to spontaneous and oxidative-stress-induced intestinal tumorigenesis.2007

    • Author(s)
      Sakamoto, K. et al.
    • Journal Title

      Cancer Res. 67(In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Significance of error-avoiding mechanisms for oxidative DNA damage in carcinogenesis.2007

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

      Cancer Sci. 98・4

      Pages: 465-470

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Measles virus infection of SLAM (CD150) knockin mice reproduces tropism and immunosuppression in human infection.2007

    • Author(s)
      Ohno, S. et al.
    • Journal Title

      J. Virol. 81・4

      Pages: 1650-1659

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Significance of error-avoiding mechanisms for oxidative DNA damage in carcinogenesis.2007

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

      Cancer Sci. 98

      Pages: 465-470

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Measles virus infection of SLAM (CD150) knockin mice reproduces tropism and immunosuppression in human infection.2007

    • Author(s)
      Ohno, S. et al.
    • Journal Title

      J.Virol. 81

      Pages: 1650-1659

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] YB-1 is important for an early stage embryonic development : neural tube formation and cell proliferation.2006

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

      J. Biol. Chem. 281・52

      Pages: 40440-40449

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Human polynucleotide phosphorylase protein in response to oxidative stress.2006

    • Author(s)
      Hayakawa, H., Sekiguchi, M.
    • Journal Title

      Biochemistry 45・21

      Pages: 6749-6755

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Prevention of radiation-induced pneumonitis by recombinant adenovirus-mediated transferring of soluble TGF-β type II receptor gene.2006

    • Author(s)
      Haiping, Z. et al.
    • Journal Title

      Cancer Gene Therapy 13

      Pages: 867-872

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Exogenous 8-oxo-dG is not utilized for nucleotide synthesis but enhances the accumulation of 8-oxo-Gua in DNA through error-prone DNA synthesis.2006

    • Author(s)
      Kim, J.-E.et al.
    • Journal Title

      Mutat. Res. 596

      Pages: 128-136

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids.2006

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

      Biol. Chem. 387

      Pages: 373-379

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] YB-1 is important for an early stage embryonic development : neural tube formation and cell proliferation.2006

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

      J.Biol.Chem. 281

      Pages: 40440-40449

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Human polynucleotide phosphorylase protein in response to oxidative stress.2006

    • Author(s)
      Hayakawa, H., Sekiguchi, M.
    • Journal Title

      Biochemistry 45

      Pages: 6749-6755

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Exogenous 8-oxo-dG is not utilized for nucleotide synthesis but enhances the accumulation of 8-oxo-Gua in DNA through error-prone DNA synthesis.2006

    • Author(s)
      Kim, J.-E.et al.
    • Journal Title

      Mutat.Res. 596

      Pages: 128-136

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids.2006

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

      Biol.Chem. 387

      Pages: 373-379

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mammalian enzymes for preventing transcriptional errors caused by oxidative damage.2005

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

      Nucl. Acids Res. 33・12

      Pages: 3779-3784

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools.2005

    • Author(s)
      Ito, R.et al.
    • Journal Title

      Biochemistry 44・17

      Pages: 6670-6674

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Two modes of microsatellite instability in human cancer : differential connection of defective DNA mismatch repair to dinucleotide repea-instability.2005

    • Author(s)
      Oda, S.et al.
    • Journal Title

      Nucl. Acids Res. 33・5

      Pages: 1628-1636

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mammalian enzymes for preventing transcriptional errors caused by oxidative damage.2005

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

      Nucl.Acids Res. 33

      Pages: 3779-3784

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools.2005

    • Author(s)
      Ito, R.et al.
    • Journal Title

      Biochemistry 44

      Pages: 6670-6674

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Two modes of microsatellite instability in human cancer : differential connection of defective DNA mismatch repair to dinucleotide repeat instability.2005

    • Author(s)
      Oda, S.et al.
    • Journal Title

      Nucl.Acids Res. 33

      Pages: 1628-1636

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Targeted disruption of one allele of the Y-box binding protein-1 (YB-1) gene in mouse embryonic stem cells and increased sensitivity to cisplatin and mitomycin C.2004

    • Author(s)
      Shibahara, K. et al.
    • Journal Title

      Cancer Sci. 95・4

      Pages: 348-353

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Targeted disruption of one allele of the Y-box binding protein-1 (YB-1) gene in mouse embryonic stem cells and increased sensitivity to cisplatin and mitomycin C.2004

    • Author(s)
      Shibahara, K. et al.
    • Journal Title

      Cancer Sci. 95

      Pages: 348-353

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] MUTYH-null mice are susceptible to spontaneous and oxidative-.stress-induced intestinal tumorigenesis.

    • Author(s)
      Sakamoto, K. et al.
    • Journal Title

      Cancer Res. 67(in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Oxidative Stress, Disease and Cancer (Singh, K K (Ed))2006

    • Author(s)
      Nakatsu Y., Sekiguchi, M.
    • Total Pages
      221-252
    • Publisher
      Imperial College Press, London
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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