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1996 Fiscal Year Final Research Report Summary

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
Keywordsmetallothionein / LEC rats / DNA damage / carcinogenesis / copper / copper-metallothionein / Wilson disease / model animal of human disease
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.

  • Research Products

    (14 results)

All Other

All Publications (14 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-03-09  

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