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Study on the mechanism of the chemical carcinogenesis of cirrhotic liver

Research Project

Project/Area Number 03670634
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionSaga Medical School

Principal Investigator

MIYAZAKI Kohji  Saga Medical School, Surgery, Assistant Professor, 医学部, 講師 (30159173)

Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsLiver cirrhosis / Chemical carcinogenesis / DNA injury / Reduced glutathione / Cytochrome P-450 / Alkaline elution / チトクロ-ムPー450
Research Abstract

The effects of reduced glutathione (GSH) and ethanol on aflatoxin B_1 AFB_1)-induced DNA single strand breaks and AFB_1-DNA adduct formation were studied in primary cultured hepatocytes. Buthionine sulphoximine (BSO) decreased intracellular GSH to 13% of those of control levels, increased DNA fragmentation of AFB_1-treated hepatocytes by over 17% of those without BSO. Thus a decrease in hepatocyte GSH levels increased AFB_1-induced DNA damage. Although ethanol in itself did not induce DNA damage, a combination of BSO and ethanol increased the percentage by over 23% of that with BSO only. BSO significantly enhanced the formation of [^3H]AFB_1-DNA adducts and ethanol further increased it in the presence of BSO, whereas ethanol did not affect the amount of GSH, total cytochrome P-450, glutathione S-transferase and epoxide hydrolase in cultured hepatocytes. However, GSH-depleted rat hepatocytes exposed to ethanol significantly increased the level of cytochrome P450IIIA, which activates AFB_1. The enhancing effects of ethanol in the presence of BSO are probably due to the induction of this enzyme in rat hepatocytes.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 宮崎 耕治: "肝・胆道癌の研究における細胞培養" 組織培養. 17. 26-29 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Nagafuchi,K.Miyazaki: "Modulation of the genotoxicity of azathioprine by intracellular gultathion in hepatocytes." J.Cancer Res.Oncol.117. 321-325 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 堤 宣翁: "アルコール性肝硬変における化学発癌の可能性とその機序" 消化器癌の発生と進展. 3. 381-384 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 宮崎 耕治: "胆道粘膜上皮細胞の初代培養ー胆道癌化学発癌物質検出のためのスクリーニング法" 消化器癌. 1. 521-524 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 堤 宣翁: "化学発癌物質スクリーニングモデルとしての肝細胞/in situニックトランスレーション法とその応用" 肝臓. 33. 161-166 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 堤 宣翁: "アルコール性肝硬変における化学発癌の可能性とその機序(第II法)" 消化器癌の発生と進展. 4. 375-377 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nagafuchi, K.: "Modulation of genotoxity of azathioprine by intracellular glutathione in hepatocytes." J. Cancer Res. Clin. Oncol.117. 321-325 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 宮崎 耕治,堤 宣翁 他: "肝・胆道癌の研究における細胞培養" 組織培養. 17. 26-29 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Nagafuchi,K.Miyazaki: "Modulation of the genotoxicity of azathioprine by intracellular glutathion in hepatocytes" J.Caneer Res.Oncol.117. 321-325 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 堤 宣翁,宮崎 耕治.他: "アルコール性肝硬変における化学発癌の可能性とその機序" 消化器癌の発生と進展. 3. 381-384 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 宮崎 耕治: "胆道粘膜上皮細胞の初代培養-胆道癌化学発癌物質検出のためのスクリーニング法" 消化器癌. 1. 521-524 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 堤 宣翁,宮崎 耕治,他: "化学発癌物質スクリーニングモデルとしての肝細胞/in situニックトランスレーション法とその応用" 肝臓. 33. 161-166 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 堤 宣翁,宮崎 耕治,他: "アルコール性肝硬変における化学発癌の可能性とその機序(第II法)" 消化器癌の発生と進展. 4. 375-377 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 宮崎 耕治、他: "肝・胆道癌の研究における細胞培養" 組織培養. 17. 26-29 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Nagafuchi,K.Miyazaki: "Modulation of the genotoxicity of azathioprine by intracellular glutathion in hepatocytes" J.Cancer Res.Oncol.117. 321-325 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 堤 宣翁、宮崎 耕治、他: "アルコ-ル性肝硬変における化学発癌の可能性とその機序" 消化器癌の発生と進展. 3. 381-384 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 宮崎 耕治: "胆道粘膜上皮細胞の初代培養ー胆道癌化学発癌物質検出のためのスクリ-ニング法" 消化器癌. 1. 521-524 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 堤 宣翁、宮崎 耕治、他: "化学発癌物質スクリ-ニングモデルとしての肝細胞/in situニックトランスレ-ション法" 肝臓. 33. 161-166 (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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