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Effects of xenobiotic-drug interaction on the expression of procarcinogen-induced genotoxicity

Research Project

Project/Area Number 21790129
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Environmental pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

SEKIMOTO Masashi  University of Shizuoka, 薬学部, 講師 (10381732)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords異物代謝酵素 / 代謝活性化 / 異物-薬物相互作用 / 発がんリスク / カルシウム拮抗薬 / 多環式芳香族炭化水素 / CYP1A酵素 / 異物排泄トランスポーター / DNA付加体 / 細胞内シグナル伝逹
Research Abstract

In this study, we examined that the effects of xenobiotic-drug interaction on the expression of procarcinogen-induced genotoxicity using experimental animals and human hepatoma cell line. Nicardipine (Nic), a dihydropyridine calcium channel blocker (DHP-CCB), increase procarcinogen (3-methylcholanthrene, MC)-mediated inductions of CYP1 enzymes and their DNA adducts formation in human hepatoma cell line. Furthermore, our preliminary experiment indicated similar interaction between MC and Nic were observed in the rat liver, lung and kidney. These findings predicted that DHP-CCB incliding Nic might increase the risk of carcinogenesis by environmental carcinogens, which are metabolically activated by CYP1 enzymes.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (34 results)

All 2011 2010 2009 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (28 results) Remarks (2 results)

  • [Journal Article] Sex- and species-differences on xenobiotic-induced toxicity : differences in constitutive and xenobiotic-mediated expression of cytochrome P450 1A subfamily enzymes (CYP1As).2011

    • Author(s)
      Sekimoto M
    • Journal Title

      Yakugaku Zasshi 131

      Pages: 415-422

    • NAID

      130000678906

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] [英名]Sex- and species-differences on xenobiotic-induced toxicity : differences in constitutive and xenobiotic-mediated expression of cytochrome P450 1A subfamily enzymes(CYP1As).[和名]化学物質の毒性発現における種差・性差の解析:シトクロムP450 1Aサブファミリー分子種(CYP1As)の発現変動における相違を指標として2011

    • Author(s)
      Masashi Sekimoto
    • Journal Title

      Yakugaku Zasshi(薬学雑誌)

      Volume: 131 Pages: 415-422

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Augmentation of 3-methyl-cholanthrene-induced bioactivation in the human hepatoma cell line HepG2 by the calcium channel blocker nicardipine.2010

    • Author(s)
      Hosaka T, Sekimoto M, Nemoto K, Degawa M
    • Journal Title

      Cancer Sci. 101

      Pages: 652-657

    • NAID

      10026589348

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Augmentation of 3-methylcholanthrene-induced bioactivation in the human hepatoma cell line HepG2 by the calcium channel blocker nicardipine.2010

    • Author(s)
      Hosaka T, Sekimoto M, Nemoto K, Degawa M.
    • Journal Title

      Cancer Sci. 101

      Pages: 652-657

    • NAID

      10026589348

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Nicardipineと3-Methylcholanthreneを複合曝露したラット肝臓および腎臓でのCYP1A酵素の相加/相乗的な誘導2011

    • Author(s)
      伝宝有美、鴨下彩加、関本征史、保坂卓臣、根本清光、出川雅邦
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-30
    • Related Report
      2010 Final Research Report
  • [Presentation] Nicardipineと3-Methylcholanthreneを複合曝露したラット肝臓および腎臓でのCYP1A酵素の相加/相乗的な誘導2011

    • Author(s)
      伝宝有美、鴨下彩加、関本征史、保坂卓臣、根本清光、出川雅邦
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      グランシップ(震災のため講演中止・誌面発表)
    • Year and Date
      2011-03-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] Effects of nicardipine on the expression of CYP1A subfamily enzymes in the rat liver and human hepatoma cell line HepG2.2011

    • Author(s)
      Sekimoto M, Hosaka T, Kamoshita A, Nemoto K, Degawa M
    • Organizer
      The 3rd JCA-AACR Special Joint Conference. The Latest Advances in Liver Cancer Research : From Basic Science to Therapeutics
    • Place of Presentation
      舞浜
    • Year and Date
      2011-03-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Effects of nicardipine on the expression of CYP1A subfamily enzymes in the rat liver and human hepatoma cell line HepG22011

    • Author(s)
      Masashi Sekimoto, Takuomi Hosaka, Ayaka Kamoshita, Kiyomitsu Nemoto, Masakuni Degawa
    • Organizer
      The 3rd JCA-AACR Special Joint Conference The Latest Advances in Liver Cancer Research : From Basic Science to Therapeutics
    • Place of Presentation
      東京ベイ舞浜ホテル、クラブリゾート
    • Year and Date
      2011-03-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] ニカルジピンと3-メチルコランスレンの複合曝露が薬物代謝酵素誘導に与える影響2010

    • Author(s)
      鴨下彩加、関本征史、保坂卓臣、根本清光、出川雅邦
    • Organizer
      第20回日本病院薬剤師会東海ブロック学術大会・平成22年度日本薬学会東海支部例会
    • Place of Presentation
      静岡
    • Year and Date
      2010-11-28
    • Related Report
      2010 Final Research Report
  • [Presentation] ニカルジピンと3-メチルコランスレンの複合曝露が薬物代謝酵素誘導に与える影響2010

    • Author(s)
      鴨下彩加、関本征史、保坂卓臣、根本清光、出川雅邦
    • Organizer
      第20回日本病院薬剤師会東海ブロック学術大会・平成22年度日本薬学会東海支部例会
    • Place of Presentation
      静岡県立大学
    • Year and Date
      2010-11-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] BCRP阻害剤Ko143はMC依存的なCYP1A1酵素誘導を増強する2010

    • Author(s)
      関本征史、保坂卓臣、内山亮太、根本清光、出川雅邦
    • Organizer
      日本環境変異原学会第39回大会
    • Place of Presentation
      つくば
    • Year and Date
      2010-11-16
    • Related Report
      2010 Final Research Report
  • [Presentation] BCRP阻害剤Ko143はMC依存的なCYP1A1酵素誘導を増強する2010

    • Author(s)
      関本征史、保坂卓臣、内山亮太、根本清光、出川雅邦
    • Organizer
      日本環境変異原学会第39回大会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2010-11-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] Dihydropyridine calcium channel blockers enhance the 3-methyl-cholanthrene-mediated induction of CYP1A1 in human hepatoma HepG2 cells.2010

    • Author(s)
      Hosaka T, Sekimoto M, Nemoto K, Degawa M
    • Organizer
      The 3rd International Conference on Health and Longevity Sciences
    • Place of Presentation
      静岡
    • Year and Date
      2010-10-16
    • Related Report
      2010 Final Research Report
  • [Presentation] Dihydropyridine calcium channel blockers enhance the 3-methylcholanthrene-mediated induction of CYP1A1 in human hepatoma HepG2 cells.2010

    • Author(s)
      Takuomi Hosaka, Masahi Sekimoto, Kiyomitsu Nemoto, Masakuni Degawa
    • Organizer
      The 3rd International Conference on Health and Longevity Sciences
    • Place of Presentation
      静岡県立大学
    • Year and Date
      2010-10-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] Augmentation of 3-methyl-cholanthrene-mediated induction of CYP1A1 by Dihydropyridine calcium channel blockers.2010

    • Author(s)
      Hosaka T, Sekimoto M, Nemoto K, Degawa M
    • Organizer
      第69回日本癌学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Final Research Report
  • [Presentation] Augmentation of 3-methylcholanthrene-mediated induction of CYP1A1 by Dihydropyridine calcium channel blockers.2010

    • Author(s)
      Takuomi Hosaka, Masahi Sekimoto, Kiyomitsu Nemoto, Masakuni Degawa
    • Organizer
      第69回日本癌学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 3-メチルコランスレンとジヒドロピリジン系カルシウム拮抗薬によるCYP1A1の相乗的誘導2010

    • Author(s)
      保坂卓臣、関本征史、根本清光、出川雅邦
    • Organizer
      第56回日本薬学会東海支部総会・大会
    • Place of Presentation
      岐阜
    • Year and Date
      2010-07-03
    • Related Report
      2010 Final Research Report
  • [Presentation] ニカルジピンのCYP1A酵素誘導作用:発がん前駆物質の代謝活性化に及ぼす影響2010

    • Author(s)
      鴨下彩加、関本征史、保坂卓臣、根本清光、出川雅邦
    • Organizer
      第56回日本薬学会東海支部総会・大会
    • Place of Presentation
      岐阜
    • Year and Date
      2010-07-03
    • Related Report
      2010 Final Research Report
  • [Presentation] ニカルジピンのCYP1A酵素誘導作用:発がん前駆物質の代謝活性化に及ぼす影響2010

    • Author(s)
      鴨下彩加、関本征史、保坂卓臣、根本清光、出川雅邦
    • Organizer
      第56回日本薬学会東海支部総会・大会
    • Place of Presentation
      岐阜薬科大学
    • Year and Date
      2010-07-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] 3-メチルコランスレンとジヒドロピリジン系カルシウム拮抗薬によるCYP1A1の相乗的誘導2010

    • Author(s)
      保坂卓臣、関本征史、根本清光、出川雅邦
    • Organizer
      第56回日本薬学会東海支部総会・大会
    • Place of Presentation
      岐阜薬科大学
    • Year and Date
      2010-07-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] Augmentation of 3-methyl-cholanthrene-mediated induction of CYP1A1 and DNA-adduct formation by nicardipine.2009

    • Author(s)
      Hosaka T, Sekimoto M, Nemoto K, Degawa M
    • Organizer
      日本環境変異原学会第38回大会
    • Place of Presentation
      静岡
    • Year and Date
      2009-11-26
    • Related Report
      2010 Final Research Report
  • [Presentation] Augmentation of 3-methylcholanthrene-mediated induction of CYP1A1 and DNA-adduct formation by nicardinine.2009

    • Author(s)
      Hosaka T, Sekimoto M, Nemoto K, Degawa M
    • Organizer
      日本環境変異原学会第38回大会
    • Place of Presentation
      清水テルサ
    • Year and Date
      2009-11-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] HepG2細胞でのニカルジピンによるCYP1A1酵素誘導に及ぼす種々リン酸化酵素阻害剤の影響2009

    • Author(s)
      内山亮太、関本征史、保坂卓臣、根本清光、出川雅邦
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2009
    • Place of Presentation
      四日市
    • Year and Date
      2009-11-23
    • Related Report
      2010 Final Research Report
  • [Presentation] HepG2細胞でのニカルジピンによるCYP1A1酵素誘導に及ぼす種々リン酸化酵素阻害剤の影響2009

    • Author(s)
      内山亮太、関本征史、保坂卓臣、根本清光、出川雅邦
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2009(三重)
    • Place of Presentation
      四日市市民会館
    • Year and Date
      2009-11-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] 3-メチルコランスレンによるCYP1A1の誘導とDNA付加体生成に対するニカルジピンの増強効果2009

    • Author(s)
      保坂卓臣、関本征史、根本清光、出川雅邦
    • Organizer
      第8回次世代を担う若手ファーマ・バイオフォーラム2009
    • Place of Presentation
      名古屋
    • Year and Date
      2009-11-15
    • Related Report
      2010 Final Research Report
  • [Presentation] 3-メチルコランスレンによるCYP1A1の誘導とDNA付加体生成に対するニカルジピンの増強効果2009

    • Author(s)
      保坂卓臣、関本征史、根本清光、出川雅邦
    • Organizer
      第8回次世代を担う若手ファーマ・バイオフォーラム2009
    • Place of Presentation
      名古屋市立大学
    • Year and Date
      2009-11-15
    • Related Report
      2009 Annual Research Report
  • [Presentation] Effect of nicardipine on chemical-mediated CYP1A1 induction in HepG2 cells.2009

    • Author(s)
      Hosaka T, Sekimoto M, Degawa M
    • Organizer
      第68回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-11
    • Related Report
      2010 Final Research Report
  • [Presentation] Effect of JNK inhibitor, SP600195, on nicardipine-mediated CYP1A1 induction in HepG2 cells.2009

    • Author(s)
      Uchiyama R, Sekimoto M, Hosaka T, Nemoto K, Degawa M
    • Organizer
      第68回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-01
    • Related Report
      2010 Final Research Report
  • [Presentation] Effect of nicardipine on chemical-mediated CYPI induction in HepG2 cells.2009

    • Author(s)
      Hosaka T, Sekimoto M, Degawa M
    • Organizer
      第68回日本癌学会学術集会(横浜)
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] Effect ofJNK inhibitor, SP600195, on nicardipine-mediated CYP1A1 induction in HepG2 cells.2009

    • Author(s)
      Uchiyama R, Sekimoto M, Hosaka T. Nemoto K, Degawa M.
    • Organizer
      第68回日本癌学会学術集会(横浜)
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] 化学物質の毒性発現における種差・性差の解析:CYP分子種の発現変動を指標として2009

    • Author(s)
      関本征史
    • Organizer
      平成21年度日本薬学会東海支部総会・大会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-07-12
    • Related Report
      2010 Final Research Report
  • [Presentation] 化学物質の毒性発現における種差・性差の解析:CYP分子種の発現変動を指標として(日本薬学会東海支部会学術奨励賞受賞講演)2009

    • Author(s)
      関本征史
    • Organizer
      平成21年度日本薬学会東海支部総会・大会
    • Place of Presentation
      愛知学院大学
    • Year and Date
      2009-07-12
    • Related Report
      2009 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.pharm.or.jp/hot-news/soreiso2.html

    • Related Report
      2010 Final Research Report
  • [Remarks] 平成21年度日本薬学会東海支部奨励賞受賞研究紹介記事

    • Related Report
      2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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