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Distribution of DNA adducts in human tissues and its pathological significance

Research Project

Project/Area Number 26670187
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Sugimura Haruhiko  浜松医科大学, 医学部, 教授 (00196742)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsDNA 付加体 / アダクトミクス / ゲノミクス / 発がん / 環境発がん / リスク / 暴露評価 / 分子病理疫学 / アダクトーム / DNA付加体 / 遺伝子多型 / 遺伝環境相関 / 肺がん / 胃がん / 大腸がん / 肝がん / 変異シグネチャー / 遺伝環境表現型相関 / エクソーム
Outline of Final Research Achievements

In this study, mass/charge value and liquid chromatography retention time of known 174 DNA addcuts were incoporated into LC-MS/MS machine (4000-QTRAP; Thermo). Using this adductome approach, three to 10 sites/case of gastric mucosa (31 cases) were investigated for DNA adducts measurements. Considerable numbers of known DNA adducts were present in human gastric mucosa in different quantities. Among them, tabacco-related adducts, lipid-peroxidation-induced DNA adducts, oxidative stress and alcohol related adducts, PhIP adduct was also noted. Tabacco-related adducts of current-smokers obviously increased as compared with that of non-smoker, but that of ex-smokers do not increase. It is assumed that tabacco-related adducts of ex-smoker diminish by epithelial cell turnover of the stomach. In the lung, adductome profile was different between smokers' and never smokers' lung; between lungs having adenocarcinoma and squamous cell carcinoma of smokers.

Report

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

    (22 results)

All 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 8 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Univ. Med. Pharm. of Tirgu-Mures(Romania)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Susceptibility to human cancer: from the perspective of a pathologist2016

    • Author(s)
      Haruhiko Sugimura
    • Journal Title

      Pathology International

      Volume: 66

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Abnormal Expressions of DNA Glycosylase Genes NEIL1, NEIL2, and NEIL3 Are Associated with Somatic Mutation Loads in Human Cancer.2016

    • Author(s)
      Shinmura K, Kato H, Kawanishi Y, Igarashi H, Goto M, Tao H, Inoue Y, Nakamura S, Misawa K, Mineta H, Sugimura H.
    • Journal Title

      Oxidative Medicine and Cellular Longevity

      Volume: 2016 Issue: 1 Pages: 1546392-1546392

    • DOI

      10.1155/2016/1546392

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Geographic particularities in incidence and etiopathogenesis of sporadic gastric cancer.2015

    • Author(s)
      KadarZ, Sugimura H et al.
    • Journal Title

      Pol J Pathol

      Volume: 66 Pages: 254-259

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Clinicopathological and Survival Analysis of Japanese Patients with Resected Non-Small-Cell Lung Cancer Harboring NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1, or PIK3CA Gene Amplification.2015

    • Author(s)
      Inoue Y, Matsuura S, Kurabe N, Kahyo T, Mori H, Kawase A, Karayama M, Inui N, Funai K, Shinmura K, Suda T, Sugimura H
    • Journal Title

      J Thorac Oncol

      Volume: 10 Issue: 11 Pages: 1590-1600

    • DOI

      10.1097/jto.0000000000000685

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New Insights in Histogenetic Pathways of Gastric Cancer.2015

    • Author(s)
      Gurzu S, Sugimura H, Orlowska J, Szentirmay Z, Jung I.
    • Journal Title

      Medicine(Baltimore)

      Volume: 94 Issue: 42 Pages: e1810-e1810

    • DOI

      10.1097/md.0000000000001810

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Gastric cancer in young vs old Romanian patients: immunoprofile with emphasis on maspin and mena protein reactivity.2015

    • Author(s)
      Gurzu S, Kadar Z, Sugimura H, Bara T, Bara T Jr, Halmaciu I, Jung I.
    • Journal Title

      APMIS

      Volume: 123 Issue: 3 Pages: 223-233

    • DOI

      10.1111/apm.12347

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cytological Features of a Variant NUT Midline Carcinoma of the Lung Harboring the NSD3-NUT Fusion Gene: A Case Report and Literature Review.2015

    • Author(s)
      Kuroda S, Suzuki S, Kurita A, Muraki M, Aoshima Y, Tanioka F, Sugimura H.
    • Journal Title

      Case Rep Pathol.

      Volume: 2015 Pages: 572951-572951

    • DOI

      10.1155/2015/572951

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] NSD3-NUT-expressing midline carcinoma of the lung: First characterization of primary cancer tissue.2015

    • Author(s)
      Suzuki S, Kurabe N, Ohnishi I, Yasuda K, Aoshima Y, Naito M, Tanioka F, Sugimura H.
    • Journal Title

      Pathol Res Pract.

      Volume: 211 Issue: 5 Pages: 404-408

    • DOI

      10.1016/j.prp.2014.10.013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Human DNA glycosylase enzyme TDG repairs thymine mispaired with exocyclic etheno-DNA adducts2014

    • Author(s)
      Goto M, Shinmura K, Matsushima Y, Ishino K, Yamada H, Totsuka Y, Matsuda T, Nakagama H, Sugimura H
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 76 Pages: 136-146

    • DOI

      10.1016/j.freeradbiomed.2014.07.044

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Robust quantitative assessments of cytosine modifications and changes in the expressions of related enzymes in gastric cancer.2014

    • Author(s)
      Du C, Kurabe N, Matsushima Y, Suzuki M, Kahyo T, Ohnishi I, Tanioka F, Tajima S, Goto M, Yamada H, Tao H, Shinmura K, Konno H, Sugimura H.
    • Journal Title

      Gastric Cancer.

      Volume: 14 Issue: 3 Pages: 409-409

    • DOI

      10.1007/s10120-014-0409-4

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Smoking-related DNA adducts in human lung and gastric tissues using adductome analysis.2016

    • Author(s)
      Kurabe N, Sugimura H et al.
    • Organizer
      AACR-JCA Joint Conference
    • Place of Presentation
      Maui, HI, USA
    • Year and Date
      2016-02-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 喫煙関連DNAアダクトのヒト組織での検出2015

    • Author(s)
      倉部誠也、椙村春彦他
    • Organizer
      日本肺がん学会
    • Place of Presentation
      横浜
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ヒトがんの個体感受性:病理からの分子疫学的アプローチ2015

    • Author(s)
      椙村春彦
    • Organizer
      第104回日本病理学会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-04-30 – 2015-05-02
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒトがんの個体感受性  :病理からの分子疫学的アプローチ2015

    • Author(s)
      Sugimura Haruhiko
    • Organizer
      日本病理学会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-04-30
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] DNA adductome analyses at multiple sites of human gastric mucosa, resected for gastric cancer2015

    • Author(s)
      Kurabe N, Sugimura H et al.
    • Organizer
      AACR 2015 Annual Meeting
    • Place of Presentation
      Philadelphia, PA, USA
    • Year and Date
      2015-04-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNA adductome analyses at multiple sites of human gastric mucosa, resected for gastric cancer2015

    • Author(s)
      Kurabe N, Ohnishi I, Sugimura H et al.
    • Organizer
      AACR (American Association for Cancer Research, Annual Meeting)
    • Place of Presentation
      Philadelphia, USA
    • Year and Date
      2015-04-18 – 2015-04-22
    • Related Report
      2014 Research-status Report
  • [Presentation] comprehensive investigation of insertional variations of human endogenous retrovirus elements in tumor tissues2015

    • Author(s)
      Kahyo T, Yamada H, Sugimura H et al.
    • Organizer
      AACR (American Association for Cancer Research, Annual Meeting)
    • Place of Presentation
      Philadelphia, USA
    • Year and Date
      2015-04-18 – 2015-04-22
    • Related Report
      2014 Research-status Report
  • [Presentation] DNA adductomics in human tissue: a clue toward the origin of human cancer?2014

    • Author(s)
      Haruhiko Sugimura
    • Organizer
      4th Asian Conference on Environmental Mutagens(India)
    • Place of Presentation
      Kolkata, India
    • Year and Date
      2014-12-12 – 2014-12-14
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] ヒト腫瘍の原因について病理はなにができるか2014

    • Author(s)
      椙村春彦
    • Organizer
      第103回日本病理学会
    • Place of Presentation
      広島
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Remarks] 浜松医科大学腫瘍病理学講座

    • URL

      http://www.hama-med.ac.jp/uni_education_igakubu_igaku_byouri1.html

    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 染色バスケット2014

    • Inventor(s)
      加茂隆春、椙村春彦 他
    • Industrial Property Rights Holder
      加茂隆春、椙村春彦 他
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-157406
    • Filing Date
      2014-08-04
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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