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DNA damage and carcinogenesis by copper-metallothionein in the LEC rats (a model animal of Wilson disease)

Research Project

Project/Area Number 07457092
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

KOJIMA Yutaka  Hokkaido University Graduate school of Environmental Earch Science Professor, 大学院・地球環境科学研究科, 教授 (50135555)

Co-Investigator(Kenkyū-buntansha) KAWANISHI Shosuke  Mie University Faculty of Medicine Professor, 医学部, 教授 (10025637)
KURASAKI Masaaki  Hokkaido University Graduate school of Environmental Earch Science Assistant, 大学院・地球環境科学研究科, 助手 (80161727)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1995: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsmetallothionein / LEC rats / DNA damage / carcinogenesis / copper / copper-metallothionein / Wilson disease / model animal of human disease / 銅メタンチオネオン / DNA切断法 / 癌 / 肝癌 / 重金属
Research Abstract

The LEC rats (Long-Evans with a cinnamon coat color) were isolated from LE rats (Long-Evans) by the difference of coat color. The LEC rats are suffered from hepatitis four months after birth. All that suffered chronic hepatitis are died by hepatic cancer.
Because of the accumulation of copper, that is, copper-metallothionein in the liver of the LEC rats, because of the appearance of hepatic cancer of all the LEC rats which escaped from the death of acute hepatitis, and because of the positive results on the DNA cleavage test by Dr.KAWANISHI of copper-metallothionein, we were interested whether the copper-metallothionein in the liver of the LEC rats demages DNA or not.
The obtained results are as follows ;
(1) It was certified that copper-metallothionein prepared by the replacement of the metals from commercially available cadmium-, zinc-metallothionein, cleaved DNA strongly.
In contrast, cadmium-and zinc-metallothionein did not cleave DNA at all.
(2) Copper-metallothionein was succeeded in the purification and isolation from the liver of the LEC rats by a newly modified method using HPLC.
With the sample, the cleavage experiment are performed at present.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Shinji OIKAWA他: "Oxidative and nonoxidative mechanisms of site-speclfic DNA cleavage induced by copper-containing" Biochemistry. 34. 8763-8770 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Masaaki KURASAKI他: "Coppre replacement of cadmium-binding α-fragment of melallothionein expressed in Escherichia coli" Research Communication in Molecular Pathology and Pharmacology. 92. 225-232 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tadasu EMOTO他: "Roles of the conserved serines of metallothionein in cadmium binding" Biuchemical Genetics. 34. 239-251 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Masaaki KURASAKI他: "Independent self-assembly of cadmium-binding α-fragment of metallothionein in Escherichia coli without porticipation of β-fiagment" Protein Engineering. 9. (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Rie YAMAGUCHI他: "A mutant metallothionein which has inrerse fragment composition exhibits high cadmum-binding abitity" Biochemistry and Molecular Biology International. 41. 49-56 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Masaaki KURASAKI他: "Significance of α-fragment of melallothionein in cacdmium-binding" Prtein Engineering. 10. (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Masaaki KURASAKI他: "Significance of α-fragment of metallothionein in cadmium-binding" Protein Engineering. 10. (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shinji OIKAWA,Masaaki KURASAKI,Yutaka KOJIMA and Shosuke KAWANISHI: "Oxidative and nonoxidative 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
      1996 Final Research Report Summary
  • [Publications] Fumitomo ODAWARA,Masaaki KURASAKI,Mika SUZUKI-KURASAKI,Shinji OIKAWA,Tadasu EMOTO,Futoshi YAMASAKI,Ana Rosa LINDE ARIAS and Yutaka KOJIMA: "Expression of human metallothionein-2 in Escherichia coli : Cadmium tolerance of transformed cells" J.Biochem.118. 1131-1137 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Masaaki KURASAKI,Futoshi YAMASAKI,Mika SUZUKI-KURASAKI,Yutaka KOJIMA: "Copper replacement of cadmium-binding alpha-fragment of metallothionein expressed in Escherichia coli" Research Communication in Molecular Pathology and Pharmacology. 92. 225-232 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tadasu EMOTO,Masaaki KURASAKI,Sinji OIKAWA,Mika SUZUKI-KURASAKI,Masashi OKABE,Futoshi YAMASAKI,and Yutaka KOJIMA: "Roles of the conserved serines of metallothionein in cadmium binding" Biochemical Genetics. 34. 239-251 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Masaaki KURASAKI,Tadasu EMOTO,Ana Rosa LINDE ARIAS,Masashi OKABE,Futoshi YAMASAKI Shinji OIKAWA and Yutaka KOJIMA: "Independent self-assembly of cadmium-binding alpha-fragment of metallothionein in Escherichia coli without participation of beta-fragment" Protein Engineering. 9. 1173-1180 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Rie YAMAGUCHI,Masaaki KURASAKI and Yutaka KOJIMA: "A mutant metallothionein which has inverse fragment composition exhibits high cadmium-binding ability" Biochemistry and Molecular Biological International. 41. 49-56 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Masaaki KURASAKI,Rie YAMAGUCHI,Ana Rosa LINDE ARIAS Masashi OKABE and Yutaka KOJIMA: "Significance of alpha-fragment of metallothionein in cadmium-binding" Protein Engineering. 10. 000-000 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shinji OIKAWA他: "Oxidative and nonoxidative mechanisms of site-speclfic DNA cleavage induced by copper-containing" Biochemistry. 34. 8763-8770 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masaaki KURASAKI他: "Copper replacement of cadmium-binding α-fragment of metallothionein experssed in Escherichia coll" Research Communication in Molecular Pathology and Pharmacology. 92. 225-232 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tadasu EMOTO他: "Roles of the conserved senines of metallothionein in cadmum binding" Biochemical Genetics. 34. 239-251 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masaaki KURASAKI他: "Independent self-assembly of cadmium-binding α-fragment of metallothinein in Escherichia coli without participation of β-tragment" Rrotein Engineering. 9. 1173-1180 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Rie YAMAGUCHI他: "A mutant methllothionein which has inverse fragment composition exhibits high cadmium-brrding ability" Biochemistry and Molecular Biology International. 41. 49-56 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masaaki KURASAKI他: "Significance of α-fragment of metallothionein in cadmium-binding" Protein Engineening. 10. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oikawa,Kurasaki,Kojima,Kawanishi;: "Oxidative and Nonoxidative Mechanisims of Site-Specific DNA cleavage Indueed by Copper-Containing Metallothioneins." Biochemistry(American Chemical Society). 34. 8763-8770 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Odawara,Kurasaki,Suzuki-Kurasaki,Oikawa,Emoto,Yamasai,Linde,Kojima;: "Expression of Human Metallothionein-2 in Escherichia coli Cadmium Telerance of Transformed Cells." J.Biochem.118. 1131-1137 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kojima,Y.and Niioka,T.: "Hygienic studies on the Federal Land Development Authority(FELDA) schemes-in Malaysia." Journal of Northem Occupational Health. 40. 51-54 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saito,S.and Kojima,Y.: "Relative Zine-binding,Capacity of Metallothionein in Hepatic Cytosols of Zine-injected Rats" Researeh Communications in Molecular Pathology and Pharmacology. 89. 199-207 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saito,S.,Yoshidzu,T.,Kojima,Y.: "Relative Zine-binding,Capacity of Metallothionein:Studies in Renal Cytosols from Zine-injected Rats" Researeh Communications in Malecular Pathology and Pharmacology. 90. 363-371 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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