• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

新規光増感剤ポルフィリン誘導体によるDNA損傷機構の解明と光線力学療法への応用

Research Project

Project/Area Number 18015024
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionSuzuka University of Medical Science

Principal Investigator

川西 正祐  Suzuka University of Medical Science, 保健衛生学部, 教授 (10025637)

Co-Investigator(Kenkyū-buntansha) 及川 伸二  三重大学, 大学院・医学系研究科, 准教授 (10277006)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2007: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2006: ¥5,600,000 (Direct Cost: ¥5,600,000)
Keywords光線力学療法 / 光増感剤 / 発がん / DNA損傷 / ポルフィリン / 一重項酸素 / 8-ニトログアニン / バイオマーカー
Research Abstract

光線力学療法(PDT)は、腫瘍組織に集積した光増感剤が励起光照射により活性酸素生成などを介してがん細胞死を引き起こす新しいがん治療法である。臨床ではデルタアミノレブリン酸(ALA)を用いたPDTが行われている。ALAは生体内縮合反応によりプロトポルフィリン(PP)に代謝され、光増感作用により抗腫瘍作用をもたらす。我々は、これまでポルフィリン誘導体(ポリカチオンポルフィリン誘導体;TMPyP)が一重項酸素を生成してHL-60細胞にアポトーシスを引き起こすことを明らかにした。本年度はHL-60を用いてTMPyPとALA由来PPの細胞膜透過性について、昨年度よりも生体内環境に近い条件で詳細な比較検討を行った。その結果、TMPyPは培地中においても核への集積性を示し、ALA由来PPよりも短時間で細胞に取り込まれた。さらに、TMPyPはALAよりも短時間でアポトーシスを誘導した。以上の結果から、TMPyPは実際に臨床で使用されているALAと同様に有用な光増感剤となることが期待され、今後さらにTMPyPによる腫瘍細胞死の分子機構の解析について検討を進める必要がある。またPPは、ferrochelataseによりFe(II)を取り込んでヘムとなり光増感作用がなくなるため、抗腫瘍効果を上げるためにはferrochelataseを抑制して光増感作用を保持することが重要である。ferrochelataseの抑制因子として一酸化窒素(NO)があり、腫瘍形成部位ではNO合成酵素の発現が増加することが多いことから、NO発生の指標でありDNA損傷塩基の薪規バイオマーカーである8-ニトログアニンを定量した。その結果、光増感剤ポルフィリン誘導体によるDNA損傷の腫瘍特異性にNOが関与している可能性が示唆され、腫瘍特異性について今後の詳細な硯究の必要性が明らかとなった。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (22 results)

All 2008 2007 2006 Other

All Journal Article (19 results) (of which Peer Reviewed: 6 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Reactive nitrogen species-dependent DNA damage in EBV-associated nasopharyngeal carcinoma: the relation to STAT3 activation and EGFR expression2008

    • Author(s)
      Ma, N., et. al.
    • Journal Title

      Int. J. Cancer 122

      Pages: 2517-2525

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of UVA-dependent DNA damage induced by an antitumor drug dacarbazine in relation to its photogenotoxicity2008

    • Author(s)
      Iwamoto, T., et. al.
    • Journal Title

      Pharm. Res. 25

      Pages: 598-604

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Photosensitized DNA damage and its protection via a novel mechanism2007

    • Author(s)
      Hiraku, Y., et. al.
    • Journal Title

      Photochem. Photobiol. 83

      Pages: 205-212

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Photosensitized DNA damage induced by NADH: site specificity and mechanism2007

    • Author(s)
      Ito, K., et. al.
    • Journal Title

      Free Radic. Res. 41

      Pages: 461-468

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 9-Nitroanthracene derivative as a precursor of anthraquinone for photodynamic therapy2007

    • Author(s)
      Fukuhara, K., et. al.
    • Journal Title

      Bioorg. Med. Chem. 15

      Pages: 3869-3873

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Guanine-specific DNA oxidation photosensitized by the tetraphenylporphyrin phosphorus (V) complex via singlet oxygen generation and electron transfer2007

    • Author(s)
      Hirakawa, K., et. al.
    • Journal Title

      J. Photochem. Photobiol. B 87

      Pages: 209-217

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 9-Nitroanthracene derivative as a precursor of anthraquinone for photodynamic therapy.2007

    • Author(s)
      Fukuhara K.
    • Journal Title

      Bioorg Med Chem. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Photosensitized DNA damage induced by NADH : site specificity and mechanism2007

    • Author(s)
      Ito, K.
    • Journal Title

      Free Radic. Res. 41 (4)

      Pages: 461-468

    • Related Report
      2006 Annual Research Report
  • [Journal Article] iNOS-dependent DNA damage in patients with malignant fibrous histiocytoma in relation to prognosis2007

    • Author(s)
      Hoki, Y.
    • Journal Title

      Cancer Sci. 98 (2)

      Pages: 163-168

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerates sarcoma development in Trp53^<+/-> mice2007

    • Author(s)
      Tazawa, H.
    • Journal Title

      Carcinogenesis 28 (1)

      Pages: 191-198

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hepatic oxidative DNA damage correlates with iron overload in chronic hepatitis C patients2007

    • Author(s)
      Fujita, N.
    • Journal Title

      Free Radic. Biol. Med. 42 (3)

      Pages: 353-362

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 特集「胸膜中皮腫の診断と治療」金属化合物およびアスベストによる酸化・ニトロ化DNA損傷2006

    • Author(s)
      平工雄介
    • Journal Title

      THE LUNG perspectives 14

      Pages: 316-321

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Oxidative and nitrative DNA damage as biomarker for carcinogenesis with special reference to inflammation2006

    • Author(s)
      Kawanishi, S.
    • Journal Title

      Antioxid. Redox Signal. 8 (5-6)

      Pages: 1047-1058

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis2006

    • Author(s)
      Kawanishi, S.
    • Journal Title

      Biol. Chem. 387 (4)

      Pages: 365-372

    • Related Report
      2006 Annual Research Report
  • [Journal Article] iNOS-dependent DNA damage via NF-κB expression in hamsters infected with Opisthorchis viverrini and its suppression by the antihelminthic drug praziquantel2006

    • Author(s)
      Pinlaor, S.
    • Journal Title

      Int. J. Cancer 119 (5)

      Pages: 1067-1072

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Critical roles for polymerase ζ in cellular tolerance to nitric oxide-induced DNA damage2006

    • Author(s)
      Wu, X
    • Journal Title

      Cancer Res. 66 (2)

      Pages: 748-754

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 8-Nitroguanine formation in oral leukoplakia, a premalignant lesion2006

    • Author(s)
      Ma, N.
    • Journal Title

      Nitric Oxide 14 (2)

      Pages: 137-143

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nitrative and oxidative DNA damage in cervical intraepithelial neoplasia associated with human papilloma virus infection

    • Author(s)
      Hiraku, Y.
    • Journal Title

      Cancer Sci. (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Photosensitized DNA damage and its protection via a novel mechanism

    • Author(s)
      Hiraku, Y.
    • Journal Title

      Photochem. Photobiol. (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Presentation] ポルフィリン類TMPyPによる細胞死誘導とDNA損傷機構:光線力学的療法への応用の可能性2007

    • Author(s)
      及川(多田)佐枝子
    • Organizer
      第29回日本光医学・光生物学会
    • Place of Presentation
      富山県富山市
    • Year and Date
      2007-07-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] 光線力学療法剤の開発:9-ニトロアントラセン誘導体からのアントラキノンの生成とDNA切断反応2007

    • Author(s)
      福原 潔
    • Organizer
      第29回日本光医学・光生物学会
    • Place of Presentation
      富山県富山市
    • Year and Date
      2007-07-13
    • Related Report
      2007 Annual Research Report
  • [Book] 化学フロンティア18ゲノム化学(齋藤烈 他編)2007

    • Author(s)
      平工雄介
    • Total Pages
      215
    • Publisher
      化学同人
    • Related Report
      2006 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi