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Assessment of combined effect of chemicals with using mutant DT40s and gene knock out Medaka.

Research Project

Project/Area Number 22390126
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionOsaka Medical College

Principal Investigator

KOUNO Kouichi  大阪医科大学, 医学部, 教授 (30111016)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Hiroyasu  大阪医科大学, 医学部, 准教授 (60340551)
Co-Investigator(Renkei-kenkyūsha) TAKEDA Shunichi  京都大学, 医学(系)研究科(研究院), 教授 (60188191)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords化学物質 / バイオアッセイ / DNA 修復経路 / 発がん性 / 変異原性 / DNA障害 / スクリーニング / 環境化学物質 / 遺伝子修復経路 / メダカ / ハイスループット / DNA修復機能 / DT40細胞
Research Abstract

The purpose of this project was to establish the assay that can be used to assess the genotoxicity of chemicals. Two methods were used to assess the genotoxicity. The first used immunostaining to reveal GammaH2ax foci, which were then counted automatically with a machine. The number of GammaH2ax foci correlated to the number of double strand brakes of DNA. The other method assessed the growth curve of mutant DT40s with impaired DNA repair pathways after chemical exposure. The genotoxicity of Monochlotoacetate (MCA) was assessed and found to cause DNA damage. Since MCA was also found to be an apoptosis inhibitor, its carcinogenicity may be aggregated. Therefore, further assessment shouldbe done carefully.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (15 results)

All 2013 2012 2011 2010

All Journal Article (10 results) (of which Peer Reviewed: 6 results) Presentation (5 results)

  • [Journal Article] Interference in DNA replication can cause mitotic chromosomal breakage unassociated with double-strand breaks.2013

    • Author(s)
      Fujita M, Sasanuma H, Yamamoto KN, Harada H, Kurosawa A, Adachi NHiraoka M, Takeda S, Hirota K.
    • Journal Title

      PLoS One.

      Volume: 8(4)

    • NAID

      120005244257

    • Related Report
      2012 Final Research Report
  • [Journal Article] Involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway.2011

    • Author(s)
      Yamamoto KN, Kobayashi S, Tsuda M, Kurumizaka H, Takata M, Kono K, Jiricny J, Takeda S, Hirota K.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 108(16) Pages: 6492-6

    • NAID

      120003072120

    • Related Report
      2012 Final Research Report
  • [Journal Article] Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair-deficient chicken DT40 cell lines.2011

    • Author(s)
      Yamamoto KN, Hirota K, Kono K, Takeda S, Sakamuru S, Xia M, Huang R, Austin CP, Witt KL, Tice RR
    • Journal Title

      Environ Mol Mutagen.

      Volume: 52(7) Pages: 547-61

    • Related Report
      2012 Final Research Report
  • [Journal Article] Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair-deficient chicken DT40 cell lines2011

    • Author(s)
      Yamamoto KN, Hirota K, Kono K, Takeda S, Sakamuru S, Xia M, Huang R, Austin CP, Witt KL, Tice RR
    • Journal Title

      Environ Mol Mutagen

      Volume: 57 Issue: 7 Pages: 547-561

    • DOI

      10.1002/em.20656

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway2011

    • Author(s)
      Yamamoto KN, Kobayashi S, Tsuda M, Kurumizaka H, Takata M, Kono K, Jiricny J, Takeda S, Hirota K
    • Journal Title

      Proc Natl Acad Sci

      Volume: 19 Pages: 6492-6496

    • NAID

      120003072120

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair-deficient chicken DT40 cell lines2011

    • Author(s)
      Yamamoto NK, Hirota K, Kono K, Takeda S, Sakamuru S, Xia M, Huang E, Christopher P.Austin, KL.Witt, Raymond R.T.
    • Journal Title

      Environmental and Molecular Mutagenesis

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutant cells defective in DNA repair pathways provide a sensitive high-throughput assay for genotoxicity.2011

    • Author(s)
      Evans TJ, Yamamoto KN, Hirota K, Takeda S.
    • Journal Title

      DNA Repair

      Volume: 10 Pages: 1292-8

    • NAID

      120002696050

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutant cells defective in DNA repair pathways provide a sensitive high-throughput assay for genotoxicity.2010

    • Author(s)
      Evans TJ, Yamamoto KN, Hirota K, Takeda S.
    • Journal Title

      DNA Repair (Amst).

      Volume: 9(12) Pages: 1292-8

    • NAID

      120002696050

    • Related Report
      2012 Final Research Report
  • [Journal Article] A stable ATP binding to the nucleotide binding domain is important for reliable gating cycle in an ABC transporter CFTR.2010

    • Author(s)
      Shimizu H, Yu YC, Kono K, Kubota T, Yasui M, Li M, Hwang TC, Sohma Y.
    • Journal Title

      J.Physiol Sci

      Volume: 60 Pages: 353-62

    • NAID

      10027504627

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Optimization of the degenerated interfacial ATP binding site improves the function of disease-related mutant cystic fibrosis transmembrane conductance regulator (CFTR) channels.2010

    • Author(s)
      Tsai MF, Jih KY, Shimizu H, Li M, Hwang TC.
    • Journal Title

      J Biol Chem.

      Volume: 285 Pages: 37663-71

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 遺伝子破壊ニワトリ B リンパ球を用いた クロロ酢酸の DNA 障害とアポトーシス阻害の検討2013

    • Author(s)
      清水 宏泰、モヒウディン、 武田 俊一 、河 野公一
    • Organizer
      第83回日本衛生学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Final Research Report
  • [Presentation] A novel bioassay to detect carbon nanotube-induced genotoxicity Mohiuddin, Islam Shamima Keka, Terry Jhon Evans, Hiroyasu Shimizu, Ko2013

    • Author(s)
      ichi Kono, Shunichi Takeda
    • Organizer
      Seishiro Hirano 28th RBC-NIRS INTERNATIONAL SYMPOSIUM
    • Place of Presentation
      Kyoto
    • Related Report
      2012 Final Research Report
  • [Presentation] 遺伝子破壊ニワトリBリンパ球を用いたクロロ酢酸のDNA障害とアポトーシス阻害の検討2013

    • Author(s)
      清水宏泰
    • Organizer
      第83回日本衛生学会総会
    • Place of Presentation
      金沢大学(金沢)
    • Related Report
      2012 Annual Research Report
  • [Presentation] A novel bioassay to detect carbon nanotube-induced genotoxicity2012

    • Author(s)
      Mohiuddin
    • Organizer
      第28回RBC-NIRS国際シンポジウム
    • Place of Presentation
      コープ・イン京都(京都)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 産業現場で使用される有害化学物質スクリーニングとしてのニワトリBリンパ球(DT40)によるバイオアッセイの確立2011

    • Author(s)
      清水宏泰、栗田晃宏、Mohiuddin、武田俊一、河野公一
    • Organizer
      近畿産業衛生学会
    • Place of Presentation
      奈良県
    • Year and Date
      2011-11-05
    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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