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Oxygen radical formation and DNA damage induced by metal compounds in relation to carcinogenicity

Research Project

Project/Area Number 06454227
Research Category

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

Allocation TypeSingle-year Grants
Research Field Hygiene
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KAWANISHI Shosuke  Kyoto Univ., Fac.of Med.lecturer, 医学研究科, 講師 (10025637)

Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordscarcinogenicity / metal compounds / DNA damage / 8-OH-dG / cultured cell / nickel compounds / inflammation / peroxynitrite / 発がん性重金属化合物 / ヒト培養細胞 / 過酸化水素 / 8-OH-デオキシグアノシン / ラット肺 / 活性酸素生成
Research Abstract

Carcinogenic chromate(VI), iron (III) -nitrilotriacetate, cobalt (II) and nickel (II) interact with hydrogen peroxide (H2O2) to generate hydroxyl free radical (OH), singlet oxygen and metal-oxygen complex causing DNA damage. The yields of 8-hydroxyl-2'-deoxyguanosine (8-OH-dG) in the cultured cells treated with nickel compounds were measured in order to clarify the participation of reactive oxygen species in nickel-induced cellular DNA damage. Treatment of cells with Ni_3S_2 or NiS for 24 hrs produced about 1.5 fold 8-OH-dG compared with untreated cells. On the other hands, since lead ions have no abilities to generate highly reactive OH and metal-oxygen complex from superoxide anion (O2^-) or H2O2, there is no possiblity that lead compounds directly participate in DNA damage through catalyzing the formation of highly reactive oxygen species. Therefore, an indirect mechanism of DNA damage induced by lead compounds should be considered. delta-Aminolevulinic acid (ALA) is a heme precursor accumulated in lead poisoning. ALA caused damage to DNA fragments obtained from c-Ha-ras protooncogene in the presence of Cu (II), but only slightly in the presence of Fe (II). Our results indicate that O2^- and H2O2 are generated during the Cu(II)-catalyzed ALA autoxidation and that H2O2 reacts with Cu (I) to form crypto-OH radical, such as Cu (I) -peroxide complex, causing DNA damage. On the basis of these findings, we have proposed that oxygen radicals may participate in metal carcinogenesis.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Y. Hiraku, et al: "Metal-mediated Oxidative Damage to Cellular and Isolated DNA by Certain Tryptophan Metabolites." Carcinogenesis,. 16. 349-356 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I. Saito, et al: "Photoactivatable DNA-Cleaving Amino Acids: Highly Sequence-Selective DNA Photocleavage by Novel-Lysine Derivatives." J. Amer. Chem. Soc.117. 5590-5591 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S. Inoue and S. Kawanishi,: "Oxidative DNA Damage Induced by Simultaneous Generation of Nitric Oxide and Superoxide." FEBS Letters.371. 86-88 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S. Oikawa, and S. Kawanishi: "Site-specilic DNA Damage Induced by NADH in the Presence of Copper(II): Role of Active Oxygen Species." Biochemistry. (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S. Oikawa, et al: "Oxidative and Non-Oxidative Mechanisms of Site-Specific DNA Cleavage Induced by Copper-Containing Metallothineins." Biochemistry,. 34. 8763-8770 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y. Hiraku and S. Kawanishi: "Mechanism of Oxidative DNA Damage Induced by δ-Aminolevulinic Acid in the Presence of Copper Ions." Cancer Res., in press. (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S. Kawanishi.: "Handbook of Experimental Pharmacology."Toxicology of Metals-Biochemical Aspects"" Springer, 32 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Hiraku, S.Inoue, S.Oikawa, K.Yamamoto, S.Tada, K.Nishino, and S.Kawanishi: "Metal-mediated Oxidative Damage to Cellular and Isolated DNA by Certain Tryptophan Metabolites." Carcinogenesis. 16. 349-356 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Saito, M.Takayama, and S.Kawanishi: "Photoactivatable DNA-Cleaving Amino Acids : Highly Sequence-Selective DNA Photocleavage by Novel-Lysine Derivatives." J.Amer.Chem.Soc.117. 5590-5591 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Oikawa, M.Kurasaki, Y.Kojima, and S.Kawanishi: "Oxidative and Non-Oxidative Mechanisms of Site-Specific DNA Cleavage Induced by Copper-Containing Metallothioneins." Biochemistry. 34. 8763-8770 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Inoue and S.Kawanishi: "Oxidative DNA Damage Induced by Simultaneous Generation of Nitric Oxide and Superoxide." FEBS Letters. 371. 86-88 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Oikawa, and S.Kawanishi: "Site-specific DNA Damage Induced by NADH in the Presence of Copper(II) : Role of Active Oxygen Species." Biochemistry. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Hiraku and S.Kawanishi: "Mechanism of Oxidative DNA Damage Induced by delta-Aminolevulinic Acid in the Presence of Copper Ions." Cancer Res.(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y. Hiraku, et al: "Metal-mediated Oxidative Damage to Cellular and Isolated DNA by Certain Tryptophan Metabolites." Carcinogenesis,. 16. 349-356 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] I. Saito, et al: "Photoactivatable DNA-Cleaving Amino Acids: Highly Sequence-Selective DNA Photocleavage by Novel-Lysine Derivatives." J. Amer. Chem. Soc.117. 5590-5591 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S. Oikawa, et al: "Oxidative and Non-Oxidative Mechanisms of Site-Specific DNA Cleavage Induced by Copper-Containing Metallothioneins." Biochemistry,. 34. 8763-8770 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S. Inoue and S. Kawanishi,: "Oxidative DNA Damage Induced by Simultaneous Generation of Nitric Oxide and Superoxide." FEBS Letters,. 371. 86-88 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S. Oikawa, and S. Kawanishi: "Site-specific DNA Damage Induced by NADH in the Presence of Copper(II): Role of Active Oxygen Species." Biochemistry,. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y. Hiraku and S. Kawanishi: "Mechanism of Oxidative DNA Damage Induced by δ-Aminolevulinic Acid in the Presence of Copper lons." Cancer Res.,. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] S. Kawanishi: "Handbook of Experimental Pharmacology. "Toxicology of Metals-Biochemical Aspects"" Springer, 32 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S. Kawanishi, et al: ""Metal and Genetics"" Marcel Dekker Inc., New York, 20 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Naito: "Role of Active Oxygen Speciesin DNA Damage by Pentachlorophencl Metabolites." Mutation Research. 310. 79-88 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Sugiyama: "Chemistry of theymal degradation of abasic sitesin DNA.Mechanistic investigation on thermal DNA Strand cleavage of alkylated DNA." Chemical Research in Toxicology. 7. 673-683 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Kawanishi: "The Role of Active Oxygen Species in DNA damage induced by Carcinogenic Metal compounds." Environmental Health Perspectives. 102. 17-20 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 川西 正祐: "金属化合物の発がん性と発がん機構" 環境保全. 9. 39-47 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Hiraku: "Metal-mediated oxidative damage to cellular and isolated DNA by certain tryptophan metabolites." Careinogenesis. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] 平工 雄介: "金属と発がん性有機化合物との相互作用による酸化的DNA損傷" 環境変異原研究. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Kawanishi: "Handbook of Experimental Pharmacology.“Toxicology of Matals-Biochemical Aspects"" Springer, 33 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Kawanishi: "Metal and Genetics" Marcel Dekker Inc.,New York, 21 (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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