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Analysis of the mechanism of tissue-specific protection of skin against the genotoxicity of ultraviolet radiation

Research Project

Project/Area Number 24310036
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionTohoku University

Principal Investigator

IKEHATA Hironobu  東北大学, 医学(系)研究科(研究院), 講師 (90250737)

Co-Investigator(Kenkyū-buntansha) KOMURA Junichiro  東北大学, 大学院医学系研究科, 助教 (10215410)
MORI Toshio  奈良県立医科大学, 医学部, 研究教授 (10115280)
Research Collaborator AIBA Setsuya  東北大学, 大学院医学系研究科, 教授
KAMEI Yasuhiro  基礎生物学研究所, 光学解析室, 特任准教授
HIGASHI Shoichi  基礎生物学研究所, 光学解析室, 技術職員
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Keywords紫外線 / 皮膚 / MIS応答 / アポトーシス / 突然変異 / DNA損傷 / 遺伝子組換えマウス
Outline of Final Research Achievements

We analyzed the mechanism of mutation induction suppression (MIS), which is a skin tissue-specific protective response to the genotoxicity of ultraviolet radiation (UV), by histological analyses and demonstrated that a tissue repair mechanism based on the apoptotic turnover of an epidermal layer was relevant. We further found that pyrimidine(6-4)pyrimidone photoproducts and their Dewar valence isomers mainly contributed to the induction of MIS response among UV-specific DNA photolesions, based on the comparative analysis between action spectra of photolesion production and MIS response and on the analysis of the interaction of MIS responses among wavelengths. We also suggested that the transcription-coupled repair pathway of nucleotide-excision DNA repair would be involved in the MIS response through genetic studies using DNA repair-deficient mice.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (21 results)

All 2015 2014 2013 2012

All Journal Article (7 results) (of which Peer Reviewed: 5 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Invited: 5 results)

  • [Journal Article] Remarkable induction of UV-signature mutations at the 3'-cytosine of dipyrimidine sites except at 5'-TCG-3' in the UVB-exposed skin epidermis of xeroderma pigmentosum variant model mice.2014

    • Author(s)
      Ikehata H, Chang Y, Yokoi M, Yamamoto M, Hanaoka F
    • Journal Title

      DNA Repair

      Volume: 22 Pages: 112-122

    • DOI

      10.1016/j.dnarep.2014.07.012

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] マウス皮膚における紫外線突然変異作用スペクトルの解析2014

    • Author(s)
      池畑広伸
    • Journal Title

      放射線生物研究

      Volume: 49 Pages: 1-13

    • NAID

      40020050262

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Action spectrum analysis of UVR genotoxicity for skin: the border wavelengths between UVA and UVB can bring serious mutation loads to skin2013

    • Author(s)
      H. Ikehata, S. Higashi, S. Nakamura, Y.Daigaku, Y. Furusawa, Y. Kamei, M. Watanabe, K. Yamamoto, K. Hieda, N. Munakata & T. Ono
    • Journal Title

      J. Invest. Dermatol

      Volume: 133 Issue: 7 Pages: 1850-1856

    • DOI

      10.1038/jid.2012.504

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Solar-UV-signature mutation prefers TCG to CCG: extrapolative consideration from UVA1-induced mutation spectra in mouse skin2013

    • Author(s)
      H. Ikehata, J. Kumagai, T. Ono & A. Morita
    • Journal Title

      Photochem. Photobiol. Sci. inpress

      Volume: 12 Issue: 8 Pages: 1319-1327

    • DOI

      10.1039/c3pp25444e

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Skin can control solar UVR-induced mutations through the epidermis-specific response of mutation induction suppression.2013

    • Author(s)
      H. Ikehata, N. Munakata, T. Ono
    • Journal Title

      Photochemical & Photobiological Sciences

      Volume: 12 Issue: 11 Pages: 2008-2015

    • DOI

      10.1039/c3pp50158b

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of the Solar-UV-Signature Mutations Detected in the p53 Gene between Mouse and Human Skin Cancers.2013

    • Author(s)
      H. Ikehata
    • Journal Title

      Photomedicine and Photobiology

      Volume: 35 Pages: 23-24

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Significance of Erythema for the Response of Mutation Induction Suppression in UV-exposed Skin.2012

    • Author(s)
      H. Ikehata, S. Higashi, Y. Kamei
    • Journal Title

      Photomed. Photobiol.

      Volume: 34 Pages: 39-40

    • Related Report
      2012 Annual Research Report
  • [Presentation] Wavelength dependence of UV photolesion formation and mutagenesis in skin2015

    • Author(s)
      Hironobu Ikehata
    • Organizer
      European Society for Photobiology Congress
    • Place of Presentation
      Aveiro, Portugal
    • Year and Date
      2015-09-03
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 色素性乾皮症バリアント群モデルマウス皮膚におけるUVB誘発突然変異スペクトルの解析2014

    • Author(s)
      池畑広伸、横井雅幸、山本雅之、花岡文雄
    • Organizer
      日本放射線影響学会第57回大会
    • Place of Presentation
      かごしま県民交流センター、鹿児島市
    • Year and Date
      2014-10-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] Wavelength dependent antigenotoxic response to UVR in skin epidermis.2014

    • Author(s)
      Hironobu Ikehata
    • Organizer
      16th International Congress on Photobiology
    • Place of Presentation
      Universidad Nacional de Cordoba, Cordoba, Argentina
    • Year and Date
      2014-09-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Why do solar-UV signature mutations occur preferentially at TCG context?2014

    • Author(s)
      Hironobu Ikehata
    • Organizer
      37th Meeting of the American Society for Photobiology
    • Place of Presentation
      Hard Rock Hotel, San Diego, USA
    • Year and Date
      2014-06-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] In vivo UVB-induced mutation spectrum in the skin epidermis of XP variant model mice2014

    • Author(s)
      H. Ikehata, M. Yokoi, M. Yamamoto, F. Hanaoka
    • Organizer
      International Symposium on Xeroderma Pigmentosum and Related Diseases: Disorders of DNA Damage Response -Bench to Bedside-
    • Place of Presentation
      Kobe International Conference Center, Kobe, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] MIS応答波長依存性に基づく紫外線治療法デザインの提案2013

    • Author(s)
      池畑広伸
    • Organizer
      第2回光皮膚科学研究会
    • Place of Presentation
      名古屋市
    • Year and Date
      2013-02-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] 皮膚がんp53遺伝子変異に見られる日光紫外線特異的突然変異の特徴2013

    • Author(s)
      池畑広伸
    • Organizer
      第35回日本光医学・光生物学会
    • Place of Presentation
      アクトシティ浜松コングレスセンター、浜松市
    • Related Report
      2013 Annual Research Report
  • [Presentation] マウス皮膚における紫外線特異的DNA損傷誘発の作用スペクトル解析2013

    • Author(s)
      池畑広伸、森俊雄、東正一、亀井保博、山本雅之
    • Organizer
      日本放射線影響学会第56回大会
    • Place of Presentation
      ホテルクラウンパレス青森、青森市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Action spectrum analysis of UVR-induced mutation in mouse skin2013

    • Author(s)
      Hironobu Ikehata
    • Organizer
      The 6th Asia and Oceania Conference on Photobiology
    • Place of Presentation
      Novotel Sydney Central, Sydney, Australia
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 紫外線の皮膚ゲノム毒性―マウスを用いた解析2013

    • Author(s)
      池畑広伸
    • Organizer
      日本環境変異原学会第42回大会
    • Place of Presentation
      岡山コンベンションセンター、岡山市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Identification and characterization of the response of mutation induction suppression (MIS) in mouse epidermis2012

    • Author(s)
      Hironobu Ikehata
    • Organizer
      The 8th 3R Symposium
    • Place of Presentation
      兵庫県淡路島
    • Year and Date
      2012-11-27
    • Related Report
      2012 Annual Research Report
  • [Presentation] M期の凝縮した染色体におけるDNA二本鎖切断の修復とその影響2012

    • Author(s)
      小村潤一郎, 池畑広伸, 小野哲也
    • Organizer
      日本放射線影響学会第55回大会
    • Place of Presentation
      仙台市
    • Year and Date
      2012-09-08
    • Related Report
      2012 Annual Research Report
  • [Presentation] 生体皮膚における紫外線ゲノム毒性に対する応答2012

    • Author(s)
      池畑広伸
    • Organizer
      日本放射線影響学会第55回大会
    • Place of Presentation
      仙台市(招待講演)
    • Year and Date
      2012-09-06
    • Related Report
      2012 Annual Research Report
  • [Presentation] 皮膚における紫外線に対する変異誘発抑制応答と紅斑反応の関連2012

    • Author(s)
      池畑広伸, 東正一, 亀井保博
    • Organizer
      第34回日本光医学・光生物学会
    • Place of Presentation
      神戸市ポートアイランド
    • Year and Date
      2012-07-27
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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