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1998 Fiscal Year Final Research Report Summary

Analysis of the human DNA damageby antioxidants for evaluation of safety in cancer chemoprevention

Research Project

Project/Area Number 09670356
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionMie University

Principal Investigator

MURATA Mariko  Mie University, Faculty of Medicine, Lecture, 医学部, 講師 (10171141)

Co-Investigator(Kenkyū-buntansha) YAMASITA Naruto  Mie University, Faculty of Medicine, Assistant, 医学部, 助手 (40263024)
KAWANISHI Shousuke  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (10025637)
Project Period (FY) 1997 – 1998
Keywordscancer chemoprevention / antioxidant / DNA damage / hydrogen peroxid / copper ion / prooxidat / alpha-tocopherol / vitamin A
Research Abstract

As a method to evaluatesafety in cancer chemoprevention, we have investigated whether antioxidants have the ability of the human DNA damage, using human cultured cells and 32P-labeledisolated DNA fragnrents of the human p53 tumor suppressor gene and c-Ha-ras-l prctooncogene. For detection of ce1lularDN.A damage, human cultured celles were treated with antioxidants, and examined by the pulsed-field get electrophoresis method. As the result. celularDNA damage was detected by the treatment of vitamin A, retinal, alpha-tocopherol and quercetin. Furthermore. we measured 8-hydroxy deoxyguanosine (8-OH-dG) formation, which was an index to an oxidative DNA lesion, quaruitativelyby HPLC-ECD.lntracellu1ar8-OH-dG formation significantly increased in cells treated with vitamin A, retinal and N-acetylcysteine. For detection of damage to isolated DN.A, antioxidants were incubated with 32P-labled DNA fragment in the presence of metalions, and the autoradiogram was obtained. alpha-Tocopherol, vitamin A, retinal, quercetin and N-acetylcysceine caused site-specific DN,A-damage in the presence of Cm(II). Catalase and bathocuproine. a Cu(I)-specific chelaror. inhibited the Co(II)-mediated DNA damage, suggesting the involvement of H_2O_2 and Curl).The DNA cleavage was observed frequency at thymine and cytosine residues in the presence of Cu(II).
So-called "antioxidants" act as antioxidants in some circumstances, but also act as prooxidants in other circumstances. In another word, antioxidants become to have ability of damaging DNA in some cases, although antioxidants protect from oxidative stress in other cases. These oxidative DNA damage could be responsible for initiation and/or tumor promotion the multi-stage of carcinogenesis. In is requested chat safety and efficacy should be estimated before recommending use of antioxidants for cancer chemopreventton.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Murata M.,: "Oxidative damage to cellular and isolated DNA by metabolites of a fungicide ortho-phenylphenol." Carcinogenesis,. 20 in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murata M.,: "Site-specific DNA methylation and apoptosis induced by diabetogenic streptozotocin." Biochemical Pharmacology. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murata M.,: "Mechanism of oxidative DNA damage induced by a heterocyclic amine, 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline." Japanese Journal of Cancer Research,. 90 in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murata M.,: "Metal-mediated DNA damage induced by diabetogenic alloxan in the presence of NADH." Free Radical Biology & Medicine,. 25. 586-595 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamashita N.,: "α-Tocopherol induces oxidative damage to DNA in the presence of copper(II) ions." Chemical Research in Toxicology,. 11. 855-862 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chen F.,: "Metal-mediated oxidative DNA damage induced by nitro-2-aminophenols." Cancer Letters,. 126. 67-74 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mariko Murata: "Oxidative damage to cellular and isolated DNA by metabolites of a fungicide ortho-phenylphenol." Carcinogenesis. 20 (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mariko Murata: "Site-specific DNA methylation and apoptosis induced by diabetogenic streptozotocin." Biochemical Pharmacology. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mariko Murata: "Mechanism of oxidative DNA damag induced by a heterocyclic amine, 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline." Japanese Journal of Cancer Research. 90 (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mariko Murata: "Metal-mediated DNA damageinduced by diabetogenic alloxan in the presence of NADH." Free Radical Biology & Medicine. 25. 586-595 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Naruto Yamashita: "alpha-Tocopherolinduces oxidative damage to DNA in the presence of copper (II) ions." Chemical Research in Toxicology. 11. 855-862 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fang Chen: "Metal-mediated oxidative DNA damage induced by nitro-2-aminophenols" Cancer Letters. 126. 67-74 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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