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Establishment of practical epigenetic toxicity evaluation system using newly developed reporter mice

Research Project

Project/Area Number 17H01882
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionHoshi University

Principal Investigator

Igarashi Katsuhide  星薬科大学, 薬学部, 教授 (30342885)

Co-Investigator(Kenkyū-buntansha) 大塚 まき  星薬科大学, 薬学部, 助手 (40734372)
山本 直樹  星薬科大学, 先端生命科学研究所, 特任助教 (50757432)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywordsエピジェネティクス / DNAメチル化 / 化学物質 / エピジェネティック毒性 / トキシコロジー / 新規レポーターマウス / ゲノム / 毒性試験 / レポーター / 有害化学物質
Outline of Final Research Achievements

With the rise of molecular and cellular biology, the epigenetic effects of chemicals have begun to be recognized as a problem in the field of toxicology. We named such toxicity epigenetic toxicity and developed a reporter assay system that can easily detect epigenetic effects of chemicals by connecting luciferase gene and tdTomato gene as reporters downstream of two promoters. We selected azacytidine as a positive chemical and examined this system, and confirmed that azacytidine increased the reporter activity and actually decreased DNA methylation. It is expected that this system will be used as a screening system for various chemicals in the future.

Academic Significance and Societal Importance of the Research Achievements

エピジェネティック毒性は潜在的リスクとして認識されていますが、実際にエピジェネティック毒性を有することが報告されている化学物質は多くありません。その理由として、エピジェネティクスには高度な分子細胞生物学的手法が必要なためと考えられます。そのような手法は毒性試験を主とする研究現場には馴染みが薄く、その結果エピジェネティック毒性が検討されないままになっています。本研究で開発したアッセイ系は培養細胞に化学物質を処理し、溶解液中の酵素活性を測定するだけで済みます。これなら毒性試験の現場でも導入可能であり、今後エピジェネティック毒性検出に活用されることが期待されます。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (14 results)

All 2021 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (4 results) (of which Invited: 3 results)

  • [Journal Article] Development of a new <i>in vitro</i> assay system for evaluating the effects of chemicals on DNA methylation2021

    • Author(s)
      Ideta-Otsuka Maky、Miyai Misato、Yamamoto Naoki、Tsuchimoto Ayaka、Tamura Hideki、Tanemura Kentaro、Shibutani Makoto、Igarashi Katsuhide
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 46 Issue: 2 Pages: 83-90

    • DOI

      10.2131/jts.46.83

    • NAID

      130007980526

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRIP12 promotes small-molecule-induced degradation through K29/K48-branched ubiquitin chains2021

    • Author(s)
      Kaiho-Soma Ai、Akizuki Yoshino、Igarashi Katsuhide、Endo Akinori、Shoda Takuji、Kawase Yasuko、Demizu Yosuke、Naito Mikihiko、Saeki Yasushi、Tanaka Keiji、Ohtake Fumiaki
    • Journal Title

      Molecular Cell

      Volume: 81 Issue: 7 Pages: 1411-1424.e7

    • DOI

      10.1016/j.molcel.2021.01.023

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant epigenetic gene regulation in hippocampal neurogenesis of mouse offspring following maternal exposure to 3,3’-iminodipropionitrile2019

    • Author(s)
      Tanaka T, Nakajima K, Masubuchi Y, Ito Y, Kikuchi S, Ideta-Ohtsuka M, Woo GH, Yoshida T, Igarashi K, Shibutani M.
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 44 Issue: 2 Pages: 93-105

    • DOI

      10.2131/jts.44.93

    • NAID

      130007590855

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant Epigenetic Gene Regulation in GABAergic Interneuron Subpopulations in the Hippocampal Dentate Gyrus of Mouse Offspring Following Developmental Exposure to Hexachlorophene.2018

    • Author(s)
      Watanabe Y, Abe H, Nakajima K, Ideta-Otsuka M, Igarashi K, Woo GH, Yoshida T, Shibutani M.
    • Journal Title

      Toxicol Sci.

      Volume: 163 Issue: 1 Pages: 13-25

    • DOI

      10.1093/toxsci/kfx291

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of doxorubicin on sperm DNA methylation in mouse models of testicular toxicity.2018

    • Author(s)
      Sakai K, Ideta-Otsuka M, Saito H, Hiradate Y, Hara K, Igarashi K, Tanemura K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 498 Issue: 3 Pages: 674-679

    • DOI

      10.1016/j.bbrc.2018.03.044

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Current State and Future Development of Epigenetic Toxicology2017

    • Author(s)
      五十嵐 勝秀、大塚(出田) まき、成田 年
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 137 Issue: 3 Pages: 265-271

    • DOI

      10.1248/yakushi.16-00230-3

    • NAID

      130005396878

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2017-03-01
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression2017

    • Author(s)
      Yamashita Michiko、Inoue Kazuki、Saeki Noritaka、Ideta-Otsuka Maky、Yanagihara Yuta、Sawada Yuichiro、Sakakibara Iori、Lee Jiwon、Ichikawa Koichi、Kamei Yoshiaki、Iimura Tadahiro、Igarashi Katsuhide、Takada Yasutsugu、Imai Yuuki
    • Journal Title

      Development

      Volume: 145 Issue: 1 Pages: 157412-157412

    • DOI

      10.1242/dev.157412

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epigenetic toxicity of environmental chemicals upon exposure during development - Bisphenol A and valproic acid may have epigenetic effects2017

    • Author(s)
      Ideta-Otsuka Maky、Igarashi Katsuhide、Narita Minoru、Hirabayashi Yoko
    • Journal Title

      Food and Chemical Toxicology

      Volume: 109 Pages: 812-816

    • DOI

      10.1016/j.fct.2017.09.014

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changes in DNA methylation in naive T helper cells regulate the pathophysiological state in minimal-change nephrotic syndrome2017

    • Author(s)
      Kobayashi Yasuko、Aizawa Akira、Takizawa Takumi、Igarashi Katsuhide、Hatada Izuho、Arakawa Hirokazu
    • Journal Title

      BMC Research Notes

      Volume: 10 Issue: 1 Pages: 480-480

    • DOI

      10.1186/s13104-017-2719-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA Methylome Analysis Identifies Transcription Factor-Based Epigenomic Signatures of Multilineage Competence in Neural Stem/Progenitor Cells.2017

    • Author(s)
      Sanosaka T, Imamura T, Hamazaki N, Chai M, Igarashi K, Ideta-Otsuka M, Miura F, Ito T, Fujii N, Ikeo K, Nakashima K
    • Journal Title

      Cell Rep

      Volume: 20 Issue: 12 Pages: 2992-3003

    • DOI

      10.1016/j.celrep.2017.08.086

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 疾患におけるエピゲノム変化の解析とエピゲノム調節をターゲットにした治療法の開発2019

    • Author(s)
      大塚まき、五十嵐勝秀
    • Organizer
      第25回日本未病システム学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] クリニカルエピゲノム研究に学ぶエピジェネティック毒性2017

    • Author(s)
      五十嵐 勝秀, 大塚 まき
    • Organizer
      第44回日本毒性学会学術年会シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ラットへのオクラトキシンA反復投与による腎臓におけるDNA修復遺伝子Rad51及びRNA翻訳制御遺伝子Rbm38のエピゲノム遺伝子発現制御の変化2017

    • Author(s)
      長谷川 也須子, 水上 さやか, 大塚(出田)まき, 五十嵐 勝秀, 吉田 敏則, 渋谷 淳
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 内分泌かく乱化学物質とエピジェネティクス2017

    • Author(s)
      五十嵐 勝秀、山本 直樹、大塚 まき
    • Organizer
      環境ホルモン学会第20回研究発表会
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2017-04-28   Modified: 2022-01-27  

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