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Development of risk evaluation method for xenobiotics based on the interindividual differences of drug-metabolizing enzymes

Research Project

Project/Area Number 23590148
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Environmental pharmacy
Research InstitutionYokohama College of Pharmacy (2013)
Okayama University (2011-2012)

Principal Investigator

HANIOKA Nobumitsu  横浜薬科大学, 薬学部, 教授 (70228518)

Co-Investigator(Kenkyū-buntansha) NARIMATSU Shizuo  岡山大学, 大学院医歯薬学総合研究科, 教授 (20113037)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords異物代謝酵素 / シトクロムP450 / UDP-グルクロン酸転移酵素 / フタル酸エステル類 / iPS細胞 / リスク評価法 / シトクロムP450(UGT) / UDP-グルクロン酸転移酵素(UGT) / フタル酸ビス(2-エチルヘキシル)(DEHP) / モノ(2-エチルヘキシル)フタレート(MEHP) / HepG2細胞 / シトクロムP450(CYP) / 転写制御因子(NR) / ヒト人工多能性幹細胞(iPS細胞)
Research Abstract

The purpose of this study was to develop risk evaluation method for environmental pollutants such as endocrine-disruptors and sick-building syndrome substances. The finding in this study suggest that diester phthalate hydrolysis activities in human liver microsomes depend on the chemical structure, and that the expression and inducibility of UGT in iPS cell-derived hepatocyte-like cells are similar that of human livers.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (41 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 9 results) Presentation (27 results) Remarks (1 results)

  • [Journal Article] Butylbenzyl phthalate hydrolysis in liver microsomes of humans, monkeys, dogs, rats and mice2014

    • Author(s)
      Takahara Y, Kinashi Y, Takahara Y, Hichiya H, Okada K, Murata M, Shigeyama M, Hanioka N
    • Journal Title

      Biol Pharm Bull

      Volume: 37 Pages: 703-706

    • NAID

      130003390976

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] cDNA cloning and functional analysis of minipig UDP-glucuronosyltransferase 1A12013

    • Author(s)
      Miyake Y, Mayumi K, Jinno H, Tanaka-Kagawa T, Narimatsu S, Hanioka N
    • Journal Title

      Biol Pharm Bull

      Volume: 36 Pages: 452-461

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of marmoset CYP2B6: cDNA cloning, protein expression and enzymatic functions2013

    • Author(s)
      Mayumi K, Hanioka N, Masuda K, Koeda A, Naito S, Miyata A, Narimatsu S
    • Journal Title

      Biochem Pharmacol

      Volume: 85 Issue: 8 Pages: 1182-1194

    • DOI

      10.1016/j.bcp.2013.01.024

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of UDP-glucuronosyltransferase 1A8 polymorphism on raloxifene glucuronidation2013

    • Author(s)
      Kokawa Y, Kishi N, Jinno H, Tanaka-Kagawa T, Narimatsu S, Hanioka N
    • Journal Title

      Eur J Pharm Sci

      Volume: 49 Issue: 2 Pages: 199-205

    • DOI

      10.1016/j.ejps.2013.03.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of animal models for intestinal first-pass metabolism of drug candidates to be metabolized by CYP3A enzymes via in vivo and in vitro oxidation of midazolam and triazolam2013

    • Author(s)
      Kuze J, Mutoh T, Takenaka T, Oda N, Hanioka N, Narimatsu S
    • Journal Title

      Xenobiotica

      Volume: 43 Issue: 7 Pages: 598-606

    • DOI

      10.3109/00498254.2012.751517

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydrolysis of di-n-butyl phthalate, butylbenzyl phthalate and di(2-ethylhexyl) phthalate in human liver microsomes2012

    • Author(s)
      Hanioka N, Takahara Y, Takahara Y, Tanaka-Kagawa T, Jinno H, Narimatsu S
    • Journal Title

      Chemosphere

      Volume: 89(9) Pages: 1112-1117

    • Related Report
      2013 Final Research Report
  • [Journal Article] Effect of aflatoxin B1 on UDP-glucuronosyltransferase mRNA expression in HepG2 cells2012

    • Author(s)
      Hanioka N, Nonaka Y, Saito K, Kataoka H, Narimatsu S
    • Journal Title

      Chemosphere

      Volume: 89(5) Pages: 526-529

    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Journal Article] Expression and inducibility of UDP-glucuronosyltransferase 1As in MCF-7 human breast carcinoma cells2012

    • Author(s)
      Hanioka N, Iwabu H, Hanafusa H, Nakada S, Narimatsu S
    • Journal Title

      Basic Clin Pharmacol Toxicol

      Volume: 110(3) Pages: 253-258

    • Related Report
      2013 Final Research Report
  • [Journal Article] Hydrolysis of di-n-butyl phthalate, butylbenzyl phthalate and di(2-ethylhexyl) phthalate in human liver microsomes2012

    • Author(s)
      Hanioka N, Takahara Y, Takahara Y, Tanaka-Kagawa T, Jinno H, Narimatsu S
    • Journal Title

      Chemospher

      Volume: 89(9) Pages: 1112-1117

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stereoselective glucuronidation of carvedilol in human liver and intestinal microsomes2012

    • Author(s)
      Hanioka N, Tanaka S, Moriguchi Y, Narimatsu S
    • Journal Title

      Pharmacology

      Volume: 90(3-4) Issue: 3-4 Pages: 117-124

    • DOI

      10.1159/000340020

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of UDP-glucuronosyltransferase 2B15 polymorphism on bisphenol A glucuronidation2011

    • Author(s)
      Hanioka N, Oka H, Nagaoka K, Ikushiro S, Narimatsu S
    • Journal Title

      Arch Toxicol

      Volume: 85(11) Pages: 1373-1381

    • Related Report
      2013 Final Research Report
  • [Journal Article] Influence of CYP2C8*13 and CYP2C8*14 alleles on amiodarone N-deethylation2011

    • Author(s)
      Hanioka N, Matsumoto K, Saito Y, Narimatsu S.
    • Journal Title

      Basic Clin Pharmacol Toxicol

      Volume: 108 Pages: 359-362

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of UDP-glucuronosyltransferase 2B15 polymorphism on bisphenol A glucuronidation2011

    • Author(s)
      Hanioka N, Oka H, Nagaoka K, Ikushiro S, Narimatsu S.
    • Journal Title

      Arch Toxicol

      Volume: 85 Pages: 1373-1381

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト及びラットUGT1A8を用いたミコフェノール酸グルクロン酸抱合反応の速度論的解析2014

    • Author(s)
      高須賀茜,須野学,伊藤雄大,埴岡伸光
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 内服抗うつ薬の簡易懸濁適応性に関する評価2014

    • Author(s)
      比知屋寛之,尾花真子,丸橋雪奈子,関野みやね,夏目敬子,春山謙斗,天野学,埴岡伸光
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] フタル酸モノ-2-エチルヘキシルの抱合反応に関与するヒトUDP-グルクロン酸転移酵素分子種2013

    • Author(s)
      鬼無悠,埴岡伸光,香川(田中)聡子,神野透人,成松鎭雄
    • Organizer
      フォーラム2013:衛生薬学・環境トキシコロジー
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒトiPS細胞由来腸管上皮細胞様細胞におけるUDP-グルクロン酸転移酵素の発現解析2013

    • Author(s)
      畠山和久,埴岡伸光,黒瀬光一,松永民秀,成松鎭雄
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Related Report
      2013 Final Research Report
  • [Presentation] フタル酸モノ-2-エチルヘキシルの抱合反応に関与するヒトUDP-グルクロン酸転移酵素分子種2013

    • Author(s)
      鬼無悠,埴岡伸光,香川(田中)聡子,神野透人,成松鎭雄
    • Organizer
      フォーラム2013:衛生薬学・環境トキシコロジー
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] イヌUDP-グルクロン酸転移酵素1A1のcDNAクローニング及びタンパク質発現2013

    • Author(s)
      廣瀨里保,三宅祐加,神野透人,香川(田中)聡子,埴岡伸光,成松鎭雄
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] マイクロ空間プレートを用いた3次元培養MCF-7細胞に及ぼすエストラジオールの影響2013

    • Author(s)
      伊豆野祥太郎,埴岡伸光,綾野賢,江尻洋子,内藤真策,成松鎭雄
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒトiPS細胞由来腸管上皮細胞様細胞におけるUDP-グルクロン酸転移酵素の発現解析2013

    • Author(s)
      畠山和久,埴岡伸光,黒瀬光一,松永民秀,成松鎭雄
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] HepG2細胞におけるフタル酸ビス(2-エチルヘキシル)及びその加水分解代謝物のシトクロムP450 mRNA発現に及ぼす影響2013

    • Author(s)
      三瀧由望,伊豆野祥太郎,神野透人,香川(田中)聡子,埴岡伸光,成松鎭雄
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒトiPS細胞由来肝細胞様細胞におけるUDP-グルクロン酸転移酵素の発現解析2012

    • Author(s)
      畠山和久,花房弘之,松永民秀,黒瀬光一,斎藤嘉朗,埴岡伸光,成松鎭雄
    • Organizer
      第53回日本生化学会中国・四国支部例会
    • Place of Presentation
      岡山(岡山大学)
    • Related Report
      2013 Final Research Report
  • [Presentation] フタル酸ジエステル類の代謝に関与する加水分解酵素の種差2012

    • Author(s)
      高原有香,高原佑輔,埴岡伸光,成松鎭雄
    • Organizer
      51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Place of Presentation
      松江(島根県民会館)
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト及びカニクイザルUDP-グルクロン酸転移酵素1A9の酵素機能比較2012

    • Author(s)
      山本康平,向井麻莉菜,岸直樹,埴岡伸光,香川(田中)聡子,神野透人,成松鎭雄
    • Organizer
      第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Place of Presentation
      松江
    • Related Report
      2012 Research-status Report
  • [Presentation] フタル酸ジエステル類の代謝に関与する加水分解酵素の種差2012

    • Author(s)
      高原有香,高原佑輔,埴岡伸光,成松鎭雄
    • Organizer
      第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Place of Presentation
      松江
    • Related Report
      2012 Research-status Report
  • [Presentation] Expression profiling of UDP-glucuronosyltransferases in HepG2 and MCF-7 cells cultured on micro-space plates2012

    • Author(s)
      伊豆野祥太郎,埴岡伸光,綾野賢,江尻洋子,内藤真策,成松鎭雄
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      千葉
    • Related Report
      2012 Research-status Report
  • [Presentation] Effect of UDP-glucuronosyltransferase 1A8 polymorphism on raloxifene glucuronidation2012

    • Author(s)
      古川由貴,岸直樹,神野透人,香川(田中)聡子,埴岡伸光,成松鎭雄
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      千葉
    • Related Report
      2012 Research-status Report
  • [Presentation] cDNA cloning and functional characterization of miniature pig UDP-glucuronosyltransferase 1A12012

    • Author(s)
      三宅祐加,真弓慶,神野透人,香川(田中)聡子,埴岡伸光,成松鎭雄
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      千葉
    • Related Report
      2012 Research-status Report
  • [Presentation] Expression of CYP and UGT mRNAs in human induced pluripotent stem cell-derived hepatocyte-like cells(ヒトiPS細胞由来肝細胞様細胞におけるCYP及びUGT mRNA解析)2011

    • Author(s)
      花房弘之,松永民秀,黒瀬光一,斎藤嘉朗,埴岡伸光,成松鎭雄
    • Organizer
      日本薬物動態学会第26回年会
    • Place of Presentation
      広島(広島国際会議場)
    • Related Report
      2013 Final Research Report
  • [Presentation] マイクロ空間プレートを用いた3次元培養HepG2細胞におけるUGT発現解析2011

    • Author(s)
      伊豆野祥太郎,埴岡伸光,江尻洋子,細田雅也,内藤真策,成松鎭雄
    • Organizer
      第52回日本生化学会中国・四国支部例会
    • Place of Presentation
      広島
    • Related Report
      2011 Research-status Report
  • [Presentation] ヒトiPS細胞由来分化肝細胞のCYP及びUGT mRNAの発現解2011

    • Author(s)
      花房弘之,埴岡伸光,松永民秀,成松鎭雄
    • Organizer
      第52回日本生化学会中国・四国支部例会
    • Place of Presentation
      広島
    • Related Report
      2011 Research-status Report
  • [Presentation] 降圧薬カルベジロールのヒト肝及び小腸ミクロゾームによるグルクロン酸抱合反応2011

    • Author(s)
      田中佐和子,埴岡伸光,成松鎭雄
    • Organizer
      第50回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Place of Presentation
      高松
    • Related Report
      2011 Research-status Report
  • [Presentation] :麻薬性鎮痛薬morphineから活性代謝物morphinone生成のin vitro解析2011

    • Author(s)
      山田奈保子,石田隆,埴岡伸光,山野茂,齋藤啓太,片岡洋行,成松鎭雄
    • Organizer
      第50回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Place of Presentation
      高松
    • Related Report
      2011 Research-status Report
  • [Presentation] Enzymatic properties of cynomolgus monkey and marmoset CYP2B6s: Comparison with human CYP2B62011

    • Author(s)
      真弓慶,埴岡伸光,増田和文,小枝暁子,内藤真策,宮田篤郎,成松鎭雄
    • Organizer
      日本薬物動態学会第26回年会
    • Place of Presentation
      広島
    • Related Report
      2011 Research-status Report
  • [Presentation] Expression of CYP and UGT mRNAs in human induced pluripotent stem cell-derived hepatocyte-like cells2011

    • Author(s)
      花房弘之,松永民秀,黒瀬光一,斎藤嘉朗,埴岡伸光,成松鎭雄
    • Organizer
      日本薬物動態学会第26回年会
    • Place of Presentation
      広島
    • Related Report
      2011 Research-status Report
  • [Presentation] How does N-glycosylation affect the enzymatic functions of UGT2B7?2011

    • Author(s)
      長岡憲次郎,埴岡伸光,生城真一,山野茂,成松鎭雄
    • Organizer
      日本薬物動態学会第26回年会
    • Place of Presentation
      広島
    • Related Report
      2011 Research-status Report
  • [Presentation] ミニブタUGT1A1のcDNAクローニング及び酵素機能

    • Author(s)
      三宅祐加,真弓慶,神野透人,香川(田中)聡子,埴岡伸光,成松鎭雄
    • Organizer
      第53回日本生化学会中国・四国支部例会
    • Place of Presentation
      岡山
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒトiPS 細胞由来肝細胞様細胞におけるUDP-グルクロン酸転移酵素の発現解析

    • Author(s)
      畠山和久,花房弘之,松永民秀,黒瀬光一,斎藤嘉朗,埴岡伸光,成松鎭雄
    • Organizer
      第53回日本生化学会中国・四国支部例会
    • Place of Presentation
      岡山
    • Related Report
      2012 Research-status Report
  • [Presentation] 変異型UGT1A8 酵素の機能:7-ヒドロキシ-4-トリフルオロメチルクマリンを基質に用いた解析

    • Author(s)
      古川由貴,岸直樹,神野透人,香川(田中)聡子,埴岡伸光,成松鎭雄
    • Organizer
      第53回日本生化学会中国・四国支部例会
    • Place of Presentation
      岡山
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.pharm.okayama-u.ac.jp/lab/xenotox/

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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