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Elucidation of the ultimate carcinogen associated with occupational cholangiocarcinoma

Research Project

Project/Area Number 26460806
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hygiene and public health
Research InstitutionThe Ohara Memorial Institute for Science of Labour (2015-2016)
Osaka City University (2014)

Principal Investigator

ENDO Ginji  公益財団法人大原記念労働科学研究所, 研究部, 客員研究員 (20160393)

Co-Investigator(Kenkyū-buntansha) 山中 健三  日本大学, 薬学部, 教授 (50182572)
加藤 孝一  日本大学, 薬学部, 教授 (60246931)
市原 学  東京理科大学, 薬学部薬学科, 教授 (90252238)
Research Collaborator SHIMODA Yasuyo  日本大学, 薬学部, 助教 (70779420)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords胆管がん / 1,2-ジクロロプロパン / ジクロロメタン / ハロゲン化炭化水素 / 化学発がん / グルタチオンS-トランスフェラーゼ / 体細胞突然変異 / 衛生 / 遺伝毒性
Outline of Final Research Achievements

The cytotoxicity of 1,2,3-trichloropropane (TCP) is higher than that of 1,2-dichloropropane (DCP). Induction of drug-metabolizing enzymes did not affect toxicity. The mRNA synthesis of GSH-regenerating enzymes is higher than those of CYPs and GSTs in TCP treated cultured cells, suggesting that the metabolic activation by GSH may be deeply involved in the toxicity rather than that by CYPs.
The experiment using human fetal liver-derived cholangiocytes showed that treatment with TNFα increased mRNA level of NFκB and an enzyme related with somatic cell hyper mutation and class switch recombination, suggesting the involvement of this enzyme with mutation of cholangiocytes.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (26 results)

All 2017 2016 2015 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (13 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] 印刷労働者における1,2-ジクロロプロパン累積曝露量と胆管がん罹患リスクの関係2017

    • Author(s)
      熊谷信二、圓藤吟史
    • Journal Title

      労働の科学

      Volume: 72 Pages: 42-45

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集 産業保健のトピックス 産業保健の最近の動向と新たな課題2016

    • Author(s)
      圓藤吟史
    • Journal Title

      公衆衛生

      Volume: 80 Issue: 4 Pages: 238-242

    • DOI

      10.11477/mf.1401208396

    • ISSN
      0368-5187, 1882-1170
    • Year and Date
      2016-04-15
    • Related Report
      2016 Annual Research Report
  • [Journal Article] Relationship between cumulative exposure to 1,2-dichloropropane and incidence risk of cholangiocarcinoma among offset printing workers.2016

    • Author(s)
      .Kumagai S, Sobue T, Makiuchi T, Kubo S, Uehara S, Hayashi T, Sato KK, Endo G.
    • Journal Title

      Occup Environ Med.

      Volume: 73 Issue: 8 Pages: 545-552

    • DOI

      10.1136/oemed-2015-103427

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of Spatial Clustering of Biliary Tract Cancer Incidence in Osaka, Japan: Neighborhood Effect of a Printing Factory2016

    • Author(s)
      Ito Y, Nakaya T, Ioka A, Nakayama T, Tsukuma H, Uehara S, Sato KK, Endo G, Hayashi T.
    • Journal Title

      Journal of Epidemiology

      Volume: 26 Issue: 9 Pages: 459-463

    • DOI

      10.2188/jea.JE20150116

    • NAID

      130005409016

    • ISSN
      0917-5040, 1349-9092
    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Screening and surveillance for occupational cholangiocarcinoma in workers exposed to organic solvents2016

    • Author(s)
      Kubo S, Takemura S, Tanaka S, Nishioka T, Kinoshita M, Hamano G, Ito T, Yamamoto T, Abue M, Aoki M, Nakagawa K, Hijioka S, Miyamoto A, Osaki Y, Endo G, Kumagai S.
    • Journal Title

      Surg Today

      Volume: 46 Issue: 6 Pages: 705-712

    • DOI

      10.1007/s00595-015-1229-9

    • NAID

      120006586208

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2020497

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemical exposure levels in printing and coating workers with cholangiocarcinoma (third report)2015

    • Author(s)
      Yamada K, Kumagai S, Kubo S, Endo G.
    • Journal Title

      Journal of Occupational Health

      Volume: 57 Issue: 6 Pages: 565-571

    • DOI

      10.1539/joh.15-0170-OA

    • NAID

      130005116263

    • ISSN
      1341-9145, 1348-9585
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recommendation of Occupational Exposure Limits (2015-2016)2015

    • Author(s)
      Endo G, Ichihara G et al.The Japan Society for Occupational Health
    • Journal Title

      Journal of Occupational Health

      Volume: 57 Issue: 4 Pages: 394-417

    • DOI

      10.1539/joh.ROEL2015

    • NAID

      130005106139

    • ISSN
      1341-9145, 1348-9585
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 職業性胆管癌の疫学的解明 (印刷会社で集団発生した胆管癌の最近の知見)2015

    • Author(s)
      圓藤 吟史
    • Journal Title

      産業医学レビュー

      Volume: 28 Pages: 147-150

    • NAID

      40020594360

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 職業性胆管癌の原因物質解明のための動物実験 (印刷会社で集団発生した胆管癌の最近の知見).2015

    • Author(s)
      市原学、張霊逸、豊國伸哉、熊谷信二
    • Journal Title

      産業医学レビュー

      Volume: 28 Pages: 151-156

    • NAID

      40020594379

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 許容濃度の勧告(2015年度)2015

    • Author(s)
      圓藤吟史、市原学ほか
    • Journal Title

      産衛誌

      Volume: 57 Pages: 146-172

    • Related Report
      2015 Research-status Report
    • Open Access
  • [Journal Article] 許容濃度の暫定値(2015)の提案理由.2015

    • Author(s)
      圓藤吟史、市原学ほか
    • Journal Title

      産衛誌

      Volume: 57 Pages: 173-217

    • Related Report
      2015 Research-status Report
    • Open Access
  • [Presentation] 1,2-ジクロロプロパンのヒト胆管細胞への曝露による遺伝子改編酵素AIDのmRNA発現上昇2017

    • Author(s)
      木村 優介,高巣 成惟,櫻井 敏博,市原 佐保子,圓藤 陽子,圓藤 吟史,市原 学.
    • Organizer
      第87回日本衛生学会学術総会
    • Place of Presentation
      宮崎市
    • Year and Date
      2017-03-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ジクロロプロパン曝露マウスの胆管細胞増殖と肝臓毒性におけるP450の役割.2017

    • Author(s)
      張 驍, 宗 才,張 霊逸,エドウィン ガーナー, 黄 晉彦,呉 文亭,常 杰,桜井 敏博, 市原 佐保子, 市原 学
    • Organizer
      第87回日本衛生学会学術総会
    • Place of Presentation
      宮崎市
    • Year and Date
      2017-03-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Exposure To 1,2-dichloropropane Enhances mRNA Expression Of Activation-induced Cytidine Deaminase In Human Cholangiocytes.2017

    • Author(s)
      Takasu S, Sakurai T, Kimura Y, Ichihara S, Endo Y, Endo G, and Ichihara G.
    • Organizer
      Society of Toxicology 56th Annual Meeting (SOT2017).
    • Place of Presentation
      ボルチモア、米国
    • Year and Date
      2017-03-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ジクロロプロパンへの曝露はヒト胆管細胞において活性化誘導シチジンデアミナーゼ発現を誘導する.2017

    • Author(s)
      市原 学、近藤直登、木村雄介、高巣成惟、櫻井敏博、市原佐保子、圓藤陽子、圓藤吟史
    • Organizer
      第16回分子予防環境医学研究会
    • Place of Presentation
      熊本市
    • Year and Date
      2017-02-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 産業中毒の原因解明と予防のための症例・疫学・実験研究-科学の本質の一つである予見性を産業医学でどのように獲得するか.2016

    • Author(s)
      市原 学
    • Organizer
      第26回日本産業衛生学会全国協議会
    • Place of Presentation
      京都市
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Role of P450 in Hepatotoxicity and Proliferation in Bile Duct Induced by Exposure to 1,2-Dichloropropane in Mice.2016

    • Author(s)
      Zhang X, Zong C, Zhang L, Garner E, Huang C, Wu W, Chang J, Sakurai T, Ichihara S, Ichihara G.
    • Organizer
      第44回産業中毒・生物学的モニタリング研究会(日本産業衛生学会)
    • Place of Presentation
      東京都
    • Year and Date
      2016-08-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 1,2-ジクロロプロパン暴露マウスの肝毒性と胆管細胞の増殖におけるP450の役割.2016

    • Author(s)
      張 驍, Cai ZONG, Lingyi ZHANG, Edwin GARNER, Chinyen HUANG, Wenting WU, Jie CHANG, 桜井 敏博, 市原 佐保子, 市原 学.
    • Organizer
      第43回日本毒性学会学術年会
    • Place of Presentation
      名古屋市
    • Year and Date
      2016-06-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] Epidemiological and Toxicological Studies on the Carcinogenicity of 1,2-dichloropropane.2016

    • Author(s)
      Ichihara G
    • Organizer
      ICCA-LRI and NIHS Workshop
    • Place of Presentation
      淡路市
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] オフセット印刷労働者におけるジクロロプロパン累積曝露量と胆管癌罹患リスク.2016

    • Author(s)
      熊谷信二、祖父江友孝、久保正二、林朝茂、佐藤恭子、上原新一郎、圓藤吟史.
    • Organizer
      第89回日本産業衛生学会
    • Place of Presentation
      福島市
    • Year and Date
      2016-05-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] オフセット印刷労働者におけるジクロロプロパン累積曝露量と胆管がん罹患リスク2016

    • Author(s)
      10.熊谷信二、祖父江友孝、久保正二、林朝茂、佐藤恭子、上原新一郎、圓藤吟史
    • Organizer
      第89回日本産業衛生学会
    • Place of Presentation
      福島市
    • Year and Date
      2016-05-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 胆管由来細胞を用いたハロゲン化炭化水素の遺伝毒性評価系の確立2015

    • Author(s)
      櫻井敏博、市原 学、高巣成惟、木村優介、圓藤陽子、圓藤吟史
    • Organizer
      日本産業衛生学会第43 回産業中毒・生物学的モニタリング研究会
    • Place of Presentation
      愛知県知多郡南知多町
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
  • [Presentation] グルタチオンS -トランスフェラーゼ肝臓内分布はジクロロプロパンによる胆 管癌誘導の種差を説明しない2015

    • Author(s)
      11.張 霊逸,宗 才,市原 佐保子,内藤 久雄,豊國 伸哉,熊谷 信二,市原 学
    • Organizer
      フォーラム2015:衛生薬学・環境トキシコロジー
    • Place of Presentation
      神戸市
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
  • [Presentation] グルタチオンS-トランスフェラーゼの肝臓内における分布は、1,2-ジクロロプロパン 曝露による胆管癌誘導作用におけるヒトとげっ歯類の違いを説明できない2015

    • Author(s)
      13.Lingyi ZHANG, Cai ZONG, 市原 佐保子, 内藤 久雄, 豊國 伸哉, 熊谷 信二, 市原 学
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      金沢市
    • Year and Date
      2015-06-29
    • Related Report
      2015 Research-status Report
  • [Remarks] 研究室メンバー - 日本大学薬学部環境衛生学

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東京理科大学 市原学教授

    • URL

      https://www.tus.ac.jp/fac_grad/p/index.php?6971

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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