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Development of a single DNA adduct-caused gene mutation assay as a model of low-dose exposure

Research Project

Project/Area Number 22710068
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Risk sciences of radiation/Chemicals
Research InstitutionNational Institute of Health Sciences

Principal Investigator

YASUI Manabu  国立医薬品食品衛生研究所, 変異遺伝部, 主任研究員 (50435707)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsトキシコロジー / DNA 付加体 / 閾値 / 放射線 / 遺伝毒性発がん物質 / 環境 / DNA付加体 / 遺伝子変異 / ターゲティング
Research Abstract

Conventional technique of investigating an influence of low-dose exposure, commonly extrapolated from high-dose to low-dose region in Toxicology, is limited. Then, we have developed a new experimental system as a model of low-dose exposure, which can be used to determine the mutagenicity of synthetic DNA adducts at exon5 of thymidine kinase gene in human lymphoblastoid TSCER122 cells, derived from TK6 cell line. As a result, when an adduct forms at least one molecule on genomic DNA, it can cause gene mutation. The observation supports the idea that genotoxic carcinogens have no thresholds for the cancer risk. However, DNA repair functions in this experimental system do not work properly. In order to confirm the existence of threshold, it is necessary to study in detail the mechanisms of a single DNA adduct-caused gene mutation using TSCER122 cells knocked out DNA repair genes.

Report

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

    (27 results)

All 2013 2012 2011 2010 Other

All Journal Article (10 results) (of which Peer Reviewed: 8 results) Presentation (16 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Miscoding properties of 8-chloro-2'-deoxyguanosine, a hypochlorous acid-induced DNA adduct,catalysed by human DNA polymerases2013

    • Author(s)
      Sassa A, Kamoshita N, Matsuda T, Ishii Y,Kuraoka I, Nohmi T, Ohta T, Honma M, and Yasui M
    • Journal Title

      Mutagenesis

      Volume: 28 Pages: 81-88

    • Related Report
      2012 Final Research Report
  • [Journal Article] Miscoding properties of 8-chloro-2'-deoxyguanosine, a hypochlorous acid-induced DNA adduct, catalysed by human DNA polymerases2013

    • Author(s)
      A. Sassa
    • Journal Title

      Mutagenesis

      Volume: 28 Issue: 1 Pages: 81-88

    • DOI

      10.1093/mutage/ges056

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of TK mutations in human lymphoblastoid TK6 cells by the rat carcinogen 3-chloro-4-(dichloromethyl)-5-hydro xy-2(5H)-furanone (MX)2011

    • Author(s)
      Hakulinen P, Yamamoto A, Koyama N, Kumita W, Yasui M, and Honma M
    • Journal Title

      Mutation Res

      Volume: 725 Issue: 1-2 Pages: 43-49

    • DOI

      10.1016/j.mrgentox.2011.07.004

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phenylalanine 171 is a molecular brake for translesion synthesis across benzo[a]pyrene-guanine adducts by human DNA polymerase kappa2011

    • Author(s)
      A. Sassa, N. Niimi, H. Fujimoto, A. Katafuchi, P. Gruz, M. Yasui, R. C. Gupta, F. Johnson, T. Ohta and T. Nohmi
    • Journal Title

      Mutat. Res.

      Volume: 718 Issue: 1-2 Pages: 10-17

    • DOI

      10.1016/j.mrgentox.2010.11.002

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acrylamide genotoxicity in young versus adult gpt delta male rats2011

    • Author(s)
      N. Koyama
    • Journal Title

      Mutagenesis

      Volume: 26 Issue: 4 Pages: 545-549

    • DOI

      10.1093/mutage/ger014

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutational specificities of brominated DNA adducts catalyzed by human DNA polymerases2011

    • Author(s)
      A. Sassa
    • Journal Title

      J.Mol.Biol

      Volume: 406 Issue: 5 Pages: 679-686

    • DOI

      10.1016/j.jmb.2011.01.005

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutational specificities of brominated DNA adducts catalyzed by human DNA polymerases.2011

    • Author(s)
      Akira Sassa (Corresponding author ; Manabu Yasui)
    • Journal Title

      Journal of Molecular Biology

      Volume: 406 Pages: 679-686

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genotoxicity of arylamide in vitro : Acrylamide is not metabolically activated in standard in vitro systems.2011

    • Author(s)
      Naoki Koyama
    • Journal Title

      Environmental Molecular Mutagenesis

      Volume: 52 Pages: 11-19

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Live cell imaging of micronucleus formation and development2010

    • Author(s)
      Yasui M, Koyama N, Koizumi T, Senda-Murata K, Takashima Y, Hayashi M, Sugimoto K, and Honma M
    • Journal Title

      Mutation Res.

      Volume: 692 Issue: 1-2 Pages: 12-18

    • DOI

      10.1016/j.mrfmmm.2010.07.009

    • Related Report
      2012 Final Research Report
  • [Journal Article] Live cell imaging of micronucleus formation and development.2010

    • Author(s)
      Manabu Yasui
    • Journal Title

      Mutation Research

      Volume: 692 Pages: 12-18

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Mutation analysis of site-specific brominated DNA adducts located in the genome of human lymphoblastoid cells2013

    • Author(s)
      Yasui M, Kanemaru Y, Kamoshita N, Sassa A, and Honma M
    • Organizer
      Mammalian DNA Repair in Gordon Research Conferences
    • Place of Presentation
      Ventura, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Mutation analysis of site-specific brominated DNA adducts located in the genome of human lymphoblastoid cells2013

    • Author(s)
      Manabu Yasui, Yuki Kanemaru, Nagisa Kamoshita, Akira Sassa, and Masamitsu Honma
    • Organizer
      Mammalian DNA Repair in Gordon Research Conferences
    • Place of Presentation
      Ventura
    • Related Report
      2012 Annual Research Report
  • [Presentation] ゲノムの特定部位に導入させたブロモ化DNA 付加体の突然変異誘発能の解析2012

    • Author(s)
      兼丸祐紀,鴨下渚,佐々彰,本間正充,安井学
    • Organizer
      日本環境変異原学会第41回大会
    • Place of Presentation
      静岡市
    • Related Report
      2012 Final Research Report
  • [Presentation] 極低線量暴露を想定した新しいDNA 付加体1分子による遺伝子変異解析系の基礎的研究2012

    • Author(s)
      安井学,鴨下渚,本間正充
    • Organizer
      日本放射線影響学会第55回大会
    • Place of Presentation
      仙台市
    • Related Report
      2012 Final Research Report
  • [Presentation] 極低線量暴露を想定した新しいDNA付加体1分子による遺伝子変異解析系の基礎的研究2012

    • Author(s)
      安井学,鴨下渚,本間正充
    • Organizer
      日本放射線影響学会
    • Place of Presentation
      仙台市
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ゲノムの特定部位に導入させたブロモ化DNA付加体の突然変異誘発能の解析2012

    • Author(s)
      兼丸祐紀,鴨下渚,佐々彰,本間正充,安井学
    • Organizer
      日本環境変異原学会
    • Place of Presentation
      静岡市
    • Related Report
      2012 Annual Research Report
  • [Presentation] ゲノムDNAに導入した1分子のDNA付加体の運命2011

    • Author(s)
      安井学, 鴨下渚, 本間正充
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Miscoding properties of brominated DNA adducts catalyzed by human DNA polymerases.2011

    • Author(s)
      Manabu Yasui
    • Organizer
      Workshop on Biomarker of Exposure and Oxidative DNA Damage in Germany
    • Place of Presentation
      ドイツ,ミュンスター
    • Year and Date
      2011-03-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] ゲノムDNAに導入した1 分子のDNA 付加体の運命2011

    • Author(s)
      安井学,鴨下渚,本間正充
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜市
    • Related Report
      2012 Final Research Report
  • [Presentation] 8-クロログアニンDNA 付加体を含むオリゴマーの構築とその誤塩基対形成機構に関する研究2011

    • Author(s)
      安井学,佐々彰,鴨下渚,松田知成,太田敏博,能美健彦,本間正充
    • Organizer
      日本環境変異原学会第40回大会
    • Place of Presentation
      東京都
    • Related Report
      2012 Final Research Report
  • [Presentation] gpt delta トランスジェニックラットを用いたライフステージ(週齢)を考慮したアクリルアミドの遺伝毒性評価2011

    • Author(s)
      小山直己,安井学,木村葵,高見成昭, 鈴木拓也,増村健一,能美健彦,増田修 一,木苗直秀,松田知成,今井俊夫,本 間正充
    • Organizer
      第38回日本トキシコロジー学会学術年会
    • Place of Presentation
      横浜市
    • Related Report
      2012 Final Research Report
  • [Presentation] Miscoding properties of brominated DNA adducts catalyzed by human DNA polymerases2011

    • Author(s)
      Yasui M, Sassa A, Ohta T, Nohmi T, and Honma M
    • Organizer
      UKEMS / Dutch EMS-sponsored Workshop on Biomarker of Exposure and Oxidative DNA Damage
    • Place of Presentation
      ミュンスター,ドイツ
    • Related Report
      2012 Final Research Report
  • [Presentation] Miscoding events during DNA synthesis past brominated DNA adducts2010

    • Author(s)
      Sassa A, Ohta T, Nohmi T, Honma M, and Yasui M
    • Organizer
      The 2nd Asian Conference of Environmental Mutagen
    • Place of Presentation
      パタヤ,タイ
    • Related Report
      2012 Final Research Report
  • [Presentation] DNA2 本鎖切断修復に対する低線量放射線等の環境ストレスの影響2010

    • Author(s)
      本間正充,安井学,堀端克良,鈴木哲矢,谷田貝文夫
    • Organizer
      第33回日本分子生物学会年会・第83 回 日本生化学会大会 合同大会
    • Place of Presentation
      横浜市
    • Related Report
      2012 Final Research Report
  • [Presentation] 臭素化DNA 付加体の誤塩基対形成機構2010

    • Author(s)
      佐々彰, 太田敏博, 能美健彦, 本間正 充, 安井学
    • Organizer
      日本環境変異原学会第39回大会
    • Place of Presentation
      つくば市
    • Related Report
      2012 Final Research Report
  • [Presentation] DNA 付加体を含む修飾DNA オリゴマーの生化学的構築法の最適化2010

    • Author(s)
      安井学, 佐々彰, 鴨下渚, 太田敏博, 松田知成, 能美健彦, 本間正充
    • Organizer
      日本環境変異原学会第39回大会
    • Place of Presentation
      つくば市
    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.nihs.go.jp/dgm/

    • Related Report
      2012 Final Research Report

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

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