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HITECマウスを用いたプラズマのゲノム影響評価

Publicly Offered Research

Project AreaPlasma medical innovation
Project/Area Number 15H00897
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Science and Engineering
Research InstitutionKyushu University

Principal Investigator

中津 可道  九州大学, 医学研究院, 准教授 (00207820)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
KeywordsDNA損傷 / 突然変異 / 細胞死 / 遺伝子改変マウス / ヒトがん細胞 / 安全評価
Outline of Annual Research Achievements

プラズマ照射は、がん細胞のアポトーシス誘導や皮膚損傷の治癒に有為な効果を示す。また、細胞膜に作用して細胞へのDNA等の物質の取り込みを促進する。これらの効果を生み出す「プラズマと生体組織の反応」の分子メカニズムには不明な点が多い。プラズマ照射の遺伝毒性に関する安全性評価の研究基盤を提供することを目的として、平成28年度は、マウス個体およびヒト細胞を用いて下記の2つの実験系でプラズマ照射によるDNA損傷や突然変異の解析を行った。
(1)マウス皮膚組織に対するプラズマ照射の影響 プラズマ照射は、遺伝子DNAを酸化して突然変異を誘発する酸素ラジカルや窒素ラジカルを発生させる。皮膚に対するプラズマ照射の影響を検討するために、空気プラズマ照射装置を用いて脱毛したマウス皮膚に8分間照射して、1時間後に安楽死させたのち解剖して皮膚組織の標本を作製し、HE染色および抗リン酸化H2AX抗体免疫染色を行った。照射中心部位では表皮細胞の核は非照射と比較してHEでは非常に弱く染色された。また、抗リン酸化H2AX抗体では全く染色されず、ネクローシスの可能性が考えられた。照射周辺部では非照射と比較して抗リン酸化H2AX抗体で非常に強く染色され、多くのDNA損傷が誘導されることが解った。プラズマ照射されたマウスの皮膚では顕著な突然変異頻度の上昇は認められなかったが、実際にヒトに照射する場合には、DNA損傷の誘発を防ぐ照射法の確立が必要と考えられる。
(2)ヒト細胞を用いたプラズマの影響 細胞へのDNA導入に有効なプラズマ源をHeLa細胞に照射して、HPRT遺伝子座を指標とした突然変異解析を行った。DNA導入が認められる10秒照射群では突然変異の上昇は認められなかったが、30秒照射群では、5~10倍の突然変異頻度の上昇が認められた。実用化には、突然変異が誘導されないプロトコールの作成が必要であると考えられた。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (20 results)

All 2017 2016 2015

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 2 results) Presentation (12 results) (of which Int'l Joint Research: 8 results,  Invited: 6 results) Book (1 results)

  • [Journal Article] Celecoxib and 2,5-dimethylcelecoxib inhibit intestinal cancer growth by suppressing the Wnt/β-catenin signaling pathway2017

    • Author(s)
      I. Egashira, F. Takahashi-Yanaga, R. Nishida, M. Arioka, K. Igawa, K. Tomooka, Y. Nakatsu, T. Tsuzuki, Y. Nakabeppu, T. Kitazono, T. Sasaguri,
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 1 Pages: 108-115

    • DOI

      10.1111/cas.13106

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BUBR1 Insufficiency in Mice Increases their Sensitivity to Oxidative Stress2016

    • Author(s)
      D. Matsuda, T. Matsumoto, K. Honma, A. Ikawa-Yoshida, M. Onimaru, T. Furuyama, Y. Nakatsu, T. Tsuzuki, Y. Maehara,
    • Journal Title

      In Vivo

      Volume: 30 Pages: 769-776

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BubR1 Insufficiency Impairs Liver Regeneration in Aged Mice after Hepatectomy through Intercalated Disc Abnormality2016

    • Author(s)
      A. Ikawa-Yoshida, T. Matsumoto, S. Okano, Y. Aoyagi, Y. Matsubara, T. Furuyama, Y. Nakatsu, T. Tsuzuki, M. Onimaru, T. Ohkusa, M. Nomura, Y. Maehara,
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 32399-32399

    • DOI

      10.1038/srep32399

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insertion and deletion mismatches distant from the target position improve gene correction with a tailed duplex.2016

    • Author(s)
      H. Kamiya*, N. Nishigaki, A. Ikeda, S. Yukawa, Y. Morita, Y. Nakatsu, T. Tsuzuki and H. Harashima
    • Journal Title

      Nucleosides Nucleotides Nucleic Acids

      Volume: 35 Issue: 7 Pages: 379-388

    • DOI

      10.1080/15257770.2016.1163384

    • NAID

      120006313423

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] BTK gene targeting by homologous recombination using a helper-dependent adenovirus/adeno-associated virus hybrid vector.2016

    • Author(s)
      Yamamoto H, Ishimura M, Ochiai M, Takada H, Kusuhara K, Nakatsu Y, Tsuzuki T, Mitani K, Hara T.
    • Journal Title

      Gene Ther

      Volume: 23 Issue: 2 Pages: 205-13

    • DOI

      10.1038/gt.2015.91

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo.2015

    • Author(s)
      Kubokura N, Takahashi-Yanaga F, Arioka M, Yoshihara T, Igawa K, Tomooka K, Morimoto S, Nakatsu Y, Tsuzuki T, Nakabeppu Y, Matsumoto T, Kitazono T, Sasaguri T
    • Journal Title

      J Pharmacol Sci

      Volume: 127 Issue: 4 Pages: 446-455

    • DOI

      10.1016/j.jphs.2015.03.005

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] UV-induced mutations in epidermal cells of mice defective in DNA polymerase η and/or ι2015

    • Author(s)
      Kanao R, Yokoi M, Ohkumo T, Sakurai Y, Dotsu K, Kura S, Nakatsu Y, Tsuzuki T, Masutani C, Hanaoka F
    • Journal Title

      DNA Repair (Amsterdam)

      Volume: S1568-7864(15) Pages: 00042-7

    • DOI

      10.1016/j.dnarep.2015.02.006

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Analyses of Oxidative Mutagenesis and Carcinogenesis Using Genetically Modified Mice: Application to Plasma Medicine2017

    • Author(s)
      Y. Nakatsu, N. Takano, M. Ohno, S. Kitazaki, K. Koga, A. Tanaka, M. Shiratani, T. Tsuzuki
    • Organizer
      4th International Workshop on Plasma for Cancer Treatment (IWPCT-2017)
    • Place of Presentation
      Paris, France
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Effects of non-thermal atmospheric air plasma irradiation on mice skin2017

    • Author(s)
      Y. Nakatsu
    • Organizer
      International Conference on Plasma Medical Science Innovation (ICPMSI) 2017
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      2017-02-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Analyses of Oxidative Mutagenesis and Carcinogenesis Using Genetically Modified Mice: Application to Plasma Medicine2016

    • Author(s)
      Y. Nakatsu
    • Organizer
      26th MRS-J Symposium:Frontier of Nano-Materials Based on Advanced Plasma Technologies
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2016-12-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mutagenesis in human and mouse cells irradiated by non-thermal atmospheric air plasma2016

    • Author(s)
      Y. Nakatsu, N. Takano, M. Ohno, S. Kitazaki, K. Koga, T. Amano, A. Tanaka, M. Hirata, M. Shiratani, T. Tsuzuki
    • Organizer
      6th international conference on plasma medicine
    • Place of Presentation
      Bratislava, Slovakia
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Time development of response of cells irradiated by non-thermal atmospheric air plasma2016

    • Author(s)
      K. Koga, T. Amano, Y. Nakatsu, H. Seo, N. Itagaki, A. Tanaka, T. Kondo, M. Shiratani
    • Organizer
      6th international conference on plasma medicine
    • Place of Presentation
      Bratislava, Slovakia
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of non-thermal atmospheric-pressure plasma irradiation on skin in hairless mice2016

    • Author(s)
      S. Kitazaki, A. Tanaka, M. Hirata, Y. Nakatsu, K. Koga, M. Shiratani
    • Organizer
      6th international conference on plasma medicine
    • Place of Presentation
      Bratislava, Slovakia
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mutyh欠損マウスを用いた酸化ストレス誘発突然変異と発がんの解析2015

    • Author(s)
      鷹野典子、大野みずき、佐々木史子、山内一己、中別府雄作、中津可道、續輝久
    • Organizer
      日本分子生物学会第38回年会・日本生化学会第88回大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 酸化ストレス誘発マウス小腸発がん実験から見えてきたこと2015

    • Author(s)
      中津可道
    • Organizer
      日本環境変異原学会第44回大会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 大野みずき、鷹野典子、佐々木史子、日高京子、中津可道、續輝久2015

    • Author(s)
      鷹野典子、大野みずき、佐々木史子、中別府雄作、日高京子、中津可道、續輝久
    • Organizer
      日本環境変異原学会第44回大会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] プラズマの直接照射及び照射溶液による突然変異の誘導2015

    • Author(s)
      中津可道、大野みずき、鷹野典子、北崎訓、古閑一憲、天野孝昭、白谷正治、田中昭代、續輝久
    • Organizer
      日本癌学会第74回学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Role of the oxidative DNA damage repair system in somatic and germline mutations in mice2015

    • Author(s)
      Mizuki Ohno, Noriko Takano, Kunihiko Sakumi, Ryutaro Fukumura, Yuki Iwasaki, Toshimichi Ikemura, Yoichi Gondo, Yusaku Nakabeppu, Yoshimichi Nakatsu, Teruhisa Tsuzuki
    • Organizer
      Zing conference "Genome Integrity"
    • Place of Presentation
      Cairns, Australia
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mismatch Repair Deficient Mice Show Susceptibility to Oxidative Stress-induced Intestinal Carcinogenesis2015

    • Author(s)
      Yoshimich Nakatsu, Jingshu Piao, Takuya Hashizume, Mizuki Ohno, Kenichi Taguchi, Teruhisa Tsuzuki
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2015-05-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Book] 日本臨牀(増刊号)最新臨床大腸癌学 基礎研究から臨床応用へ (Ⅲ-2-(6))酸化DNA損傷と大腸発癌)2015

    • Author(s)
      續輝久、大野みずき、中津可道
    • Total Pages
      715
    • Publisher
      株式会社 日本臨牀社
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2018-03-28  

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