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Formation of DNA adducts and mechanism of mutagenesis induced by nanomaterials

Research Project

Project/Area Number 23710084
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Risk sciences of radiation/Chemicals
Research InstitutionNippon Medical School (2013)
National Center of Neurology and Psychiatry (2011-2012)

Principal Investigator

ISHINO Kousuke  日本医科大学, 医学部, 助教 (60584878)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsDNA付加体 / 突然変異 / ナノマテリアル / 酸化ストレス / LC-MS/MS / アダクトミクス / マグネタイト / アダクトーム解析
Research Abstract

Nanomaterials are useful owing to their characteristic properties and are commonly used in various fields. Nanosized magnetite (MGT) is widely utilized in medicinal and industrial fields; however, their toxicological properties are not well studied. In our previous study, we found that DNA damage analyzed by the comet assay of the lungs of ICR mice intratracheally instilled with a single dose of MGT at 0.05 or 0.2 mg/animal was approximately two- to three-fold greater than that of vehicle-instilled ICR mice. In this study, a comprehensive DNA adduct analysis (DNA adductome) revealed that a broad array of DNA adducts, including etheno-dA and heptanone-etheno-dC, were produced and that most of the DNA adducts determined as the major contributors in the MGT-exposed group could be derived from inflammation. These findings suggest that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (14 results)

All 2014 2013 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (9 results) Remarks (1 results)

  • [Journal Article] Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response2014

    • Author(s)
      Totsuka Y, Ishino K, Kato T, Goto S, Tada Y, Nakae D, Watanabe M, Wakabayashi K
    • Journal Title

      Nanomaterials

      Volume: 4 Issue: 1 Pages: 175-188

    • DOI

      10.3390/nano4010175

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genotoxicity and reactive oxygen species production induced by magnetite nanoparticles in mammalian cells2013

    • Author(s)
      Kawanishi M, Ogo S, Ikemoto M, Totsuka Y, Ishino K, Wakabayashi K, Yagi T
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 38 Issue: 3 Pages: 503-511

    • DOI

      10.2131/jts.38.503

    • NAID

      10031158916

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay systems2012

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

      Nanotoxicology

      Volume: (in press) Issue: 4 Pages: 452-461

    • DOI

      10.3109/17435390.2012.674571

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] In Vitro and In Vivo Genotoxicity Induced by Fullerene (C60) and Kaolin2011

    • Author(s)
      Totsuka Y, Kato T, Masuda S, Ishino K, Matsumoto Y, Goto S, Kawanishi M, Tagi T, Wakabayashi K
    • Journal Title

      Genes and Environment

      Volume: 33 Issue: 1 Pages: 14-20

    • DOI

      10.3123/jemsge.33.14

    • NAID

      10027955671

    • ISSN
      1880-7046, 1880-7062
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] Analysis of DNA damage induced by nanomaterials using comprehensive analysis of DNA adducts (DNA adductome analysis)2012

    • Author(s)
      Kousuke Ishino, Akihiro Sekine, Sumio Goto, Hitoshi Nakagama, Yukari Totsuka
    • Organizer
      3rd Asian Conference on Environmental Mutagens
    • Place of Presentation
      Hangzhou, China
    • Related Report
      2013 Final Research Report
  • [Presentation] DNA付加体の網羅的解析による新規付加体の探索2012

    • Author(s)
      石野孔祐、関根彬弘、後藤純雄、中釜斉、戸塚ゆ加里
    • Organizer
      日本環境変異原学会第41回大会
    • Place of Presentation
      静岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Analysis of DNA damage induced by nanomaterials using comprehensive analysis of DNA adducts (DNA adductome analysis)2012

    • Author(s)
      Ishino K, Sekine A, Goto S, Nakagama H, Totsuka Y
    • Organizer
      3rd Asian Conference on environmental mutagens
    • Place of Presentation
      中国杭州
    • Related Report
      2012 Research-status Report
  • [Presentation] DNA付加体の網羅的解析による新規付加体の探索2012

    • Author(s)
      石野孔祐、関根彬弘、後藤純雄、中釜 斉、戸塚ゆ加里
    • Organizer
      第41回大会日本環境変異原学会
    • Place of Presentation
      静岡
    • Related Report
      2012 Research-status Report
  • [Presentation] ナノマテリアルにより誘発されるDNA付加体の網羅的解析2011

    • Author(s)
      石野孔祐
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-05
    • Related Report
      2011 Research-status Report
  • [Presentation] ナノマテリアルによりマウス肺に誘発されるDNA付加体の網羅的解析2011

    • Author(s)
      石野孔祐
    • Organizer
      第59回質量分析総合討論会
    • Place of Presentation
      吹田
    • Year and Date
      2011-09-13
    • Related Report
      2011 Research-status Report
  • [Presentation] ナノマテリアルによりマウス肺に誘発される DNA付加体の網羅的解析2011

    • Author(s)
      石野孔祐、加藤竜也、戸塚ゆ加里、中釜斉
    • Organizer
      第59回質量分析総合討論会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] A comprehensive analysis of DNAadducts in mice exposed to nanomaterials2011

    • Author(s)
      石野孔祐、戸塚ゆ加里、加藤竜也、中釜斉
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] ナノマテリアルによりマウス肺に誘発されるDNA付加体の網羅的解析2011

    • Author(s)
      石野孔祐、加藤竜也、松田知成、戸塚ゆ加里、中釜斉
    • Organizer
      日本環境変異原学会第40回大会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Remarks]

    • URL

      http://www.nms-pathology.com/

    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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