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酸化ストレスマーカー、8-ヒドロキシグアニンによるアスベスト発がんリスクの予測

Research Project

Project/Area Number 18014026
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

葛西 宏  University of Occupational and Environmental Health, Japan, 産業生態科学研究所, 教授 (40152615)

Co-Investigator(Kenkyū-buntansha) 河井 一明  産業医科大学, 産業生態科学研究所, 准教授 (60161262)
高橋 謙  産業医科大学, 産業生態科学研究所, 教授 (90226829)
李 云善  産業医科大学, 産業生態科学研究所, 助教 (90449950)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥8,900,000 (Direct Cost: ¥8,900,000)
Fiscal Year 2007: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥5,200,000 (Direct Cost: ¥5,200,000)
Keywordsアスベスト / 酸化ストレス / 8-OH-dG / 8-OH-Gua / 8-ヒドロキシデオキシグアノシン / 8-ヒドロキシグアニン
Research Abstract

1)酸化ストレスマーカーとしての細胞DNA、尿、血清中8-ヒドロキシデオキシグアノシン(8-OH-dG)および遊離塩基8-ヒドロキシグアニン(8-OH-Gua)の分析法の改善を試みた。DNA中8-OH-dG測定に関してはサンプルの保存温度が、測定値の再現性や正確さに大きく影響するため、測定直前まで-80℃に保存することが重要であることがわかった。一方、尿、血清中の8-OH-dG、8-OH-Guaの分析に関しては卵白を蛋白源とした餌で動物実験を行うことによりバックグラウンドを下げることができた。これらの分析法を用いて、比較的低線量(2-10Gy)の照射で8-OH-dG,8-OH-Guaの明確な増加が観察できるようになった。この分析法はアスベスト発がんにおける酸化ストレスの測定法として応用が期待される。
2)中国で過去にアスベスト関連の仕事に従事した労働者126名と対照群66名から尿を採取し8-OH-dGをHPLC-ECD法により測定した。8-OH-dG値は心臓病(P=0.0245)、神経衰弱(P=0.0089)と正の相関が見られたがアスベスト関連職業との関連は見られなかった。
3)F344ラットの腹腔内にアスベスト(クリソタイル)を投与し経時的に尿中8-OH-dGおよび血清中8-OH-GuaをHPLC-ECD法により測定した。両マーカーとも上昇傾向がみられた。同様の条件でラットに中皮腫が発生することからアスベストによる中皮腫発生に活性酸素が関与していることが示唆された。

Report

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

    (24 results)

All 2007 2006

All Journal Article (18 results) Presentation (5 results) Book (1 results)

  • [Journal Article] Prospective study of urinary excretion of 7-methylguanine and the risk of lung cancer: Effect modification by mu class glutathione-S-transferases.2007

    • Author(s)
      Loft S
    • Journal Title

      Int J Cancer. 121

      Pages: 1579-84

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Increased levels of 8-hydroxy-2'-deoxyguanosine in Drosophila larval DNA after irradiation with 364-nm laser light but not with X-rays2007

    • Author(s)
      Negishi T
    • Journal Title

      Photochemistry and Photobiology 83

      Pages: 658-663

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Body mass index and oxidative DNA damage: A longitudinal study.2007

    • Author(s)
      Mizoue T
    • Journal Title

      Cancer Sci. 98

      Pages: 1254-1258

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 2-Hydroxy-2'-deoxyadenosine 5'-triphosphate enhances A.T -> C.G mutations caused by 8-hydroxy-2'-deoxyguanosine 5'-triphosphate by suppressing its degradation upon replication in a HeLa extract.2007

    • Author(s)
      Satou K
    • Journal Title

      Biochemistry 46

      Pages: 6639-46

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells.2007

    • Author(s)
      Satou K
    • Journal Title

      Free Radic Biol Med. 42

      Pages: 1552-60

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Analysis of 8-hydroxy-2'-deoxyguanosine in urine using high-performance liquid chromatography-electrospray tandem mass spectrometry.2007

    • Author(s)
      Harri M
    • Journal Title

      J Chromatogr B Analyt Technol Biomed Life Sci. 853

      Pages: 242-6

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Accurate measurement of 8-OH-dG and 8-OH-Gua in mouse DNA, urine and serum; Effect of X-irradiation2007

    • Author(s)
      Kawai K
    • Journal Title

      Genes and Environment 29

      Pages: 107-114

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Increase of Urinary 8-OH-dG Levels after Administration of a Vitamin-deficient Diet and a Sweet Beverage2007

    • Author(s)
      Li YS
    • Journal Title

      Genes and Environment 29

      Pages: 128-132

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Ecological association between asbestos-related diseases and historical asbestos consumption : an international analysis.2007

    • Author(s)
      Lin RT
    • Journal Title

      Lancet 369

      Pages: 844-849

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Formation of 8-hydroxy-2'-deoxyguanosine in the DNA of cultured human keratinocytes by clinically used doses of narrowband and broadband ultraviolet B and psoralen plus ultraviolet A.2006

    • Author(s)
      Orimo H
    • Journal Title

      Cancer Sci. 97

      Pages: 99-105

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Leanness, smoking, and enhanced oxidative DNA damage.2006

    • Author(s)
      Mizoue T
    • Journal Title

      Cancer Epidemiol Biomarkers Prev. 15

      Pages: 582-585

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Absence of in vivo genotoxic potential and tumor initiation activity of kojic acid in the rat thyroid.2006

    • Author(s)
      Tamura T
    • Journal Title

      Toxicology 222

      Pages: 213-224

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cloning and characterization of an ascidian homolog of the human 8-oxoguanine DNA glycosylase (Ogg1) that is involved in the repair of 8-oxo-7,8-dihydroguanine in DNA in Ciona intestinalis.2006

    • Author(s)
      Jin G
    • Journal Title

      Int J Radiat Biol 82

      Pages: 241-250

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Urinary 8-hydroxyguanine may be a better marker of oxidative stress than 8-hydroxydeoxyguanosine in relation to the life spans of various species.2006

    • Author(s)
      Svoboda P
    • Journal Title

      Antioxid Redox Signal 8

      Pages: 985-992

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Contrasting Genome-Wide Distribution of 8-Hydroxyguanine and Acrolein-Modified Adenine during Oxidative Stress-Induced Renal Carcinogenesis.2006

    • Author(s)
      Akatsuka S
    • Journal Title

      Am J Pathol 169

      Pages: 1328-1342

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Detection of genotoxic nucleosides, 8-hydroxydeoxyguanosine, 8-hydroxyguanosine and free base 8-hydroxyguanine in fish food products.2006

    • Author(s)
      Kawai K
    • Journal Title

      Genes and Environment 28

      Pages: 120-122

    • NAID

      110004793042

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Fragmentation of the DNA repair enzyme, OGG1, in mouse nonparenchymal liver cells by arsenic compounds.2006

    • Author(s)
      Hirano T
    • Journal Title

      Genes and Environment 28

      Pages: 62-67

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Evaluation of oxidative damage induced by natural sunlight in drosophila.2006

    • Author(s)
      Arakawa R
    • Journal Title

      Genes and Environment 28

      Pages: 153-159

    • Related Report
      2006 Annual Research Report
  • [Presentation] X線照射により誘導される生体内酸化ストレスマーカー2007

    • Author(s)
      河井 一明
    • Organizer
      第50回大会日本放射線影響学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-16
    • Related Report
      2007 Annual Research Report
  • [Presentation] アスベスト発がんにおける活性酸素の関与とボイセンベリーによる中皮腫の抑制2007

    • Author(s)
      安達修一
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] ビタミン欠乏食、甘味飲料摂取によるマウス尿中8-OH-dGの上昇2007

    • Author(s)
      葛西 宏
    • Organizer
      がん予防大会
    • Place of Presentation
      東京
    • Year and Date
      2007-07-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] ビタミン欠乏食、甘味飲料摂取による尿中8-OH-dGの上昇2007

    • Author(s)
      葛西 宏
    • Organizer
      第29回日本フリーラジカル学会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-06-09
    • Related Report
      2007 Annual Research Report
  • [Presentation] 酸化ストレスマーカーとしての8-OH-dG及び遊離塩基8-OH-Guaの有用性2007

    • Author(s)
      河井 一明
    • Organizer
      第29回日本フリーラジカル学会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-06-09
    • Related Report
      2007 Annual Research Report
  • [Book] Oxidative Damage to Nucleic Acids2007

    • Author(s)
      H. Kasai
    • Publisher
      Analysis of 8-hydroxy-2'-deoxyguanosine as a marker of oxidatively damaged DNA in relation to carcinogenesis and aging.
    • Related Report
      2007 Annual Research Report

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

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