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

铜金属硫蛋白对 LEC 大鼠（威尔逊病模型动物）的 DNA 损伤和致癌作用

• 批准号: 07457092
• 负责人: KOJIMA Yutaka
• 金额: $ 1.92万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457092/
• 关键词: metallothionein; 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

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.

LEC大鼠(Long-Evans，肉桂皮色)与LE大鼠(Le-Evans，Long-Evans，毛色不同)分离。LEC大鼠在出生四个月后患上肝炎。所有慢性肝炎患者均死于肝癌。由于LEC大鼠肝脏中铜-金属硫蛋白的蓄积，由于所有逃脱急性肝炎死亡的LEC大鼠都出现了肝癌，以及由于Kawanishi博士对铜-金属硫蛋白的DNA裂解试验阳性，我们对LEC大鼠肝脏中的铜-金属硫蛋白是否损伤DNA感兴趣。(1)从市售的镉、锌金属硫蛋白中替代金属制备的铜金属硫蛋白对DNA有较强的切割作用，而镉、锌金属硫蛋白则完全不切割DNA。(2)用一种新的改良方法从LEC大鼠的肝脏中分离纯化铜金属硫蛋白。

项目成果

Tadasu EMOTO他: "Roles of the conserved serines of metallothionein in cadmium binding" Biuchemical Genetics. 34. 239-251 (1996)

Tadasu EMOTO 等人：“金属硫蛋白保守丝氨酸在镉结合中的作用”Biuchemical Genetics 34. 239-251 (1996)

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)

Tadasu EMOTO、Masaaki KURASAKI、Sinji OIKAWA、Mika SUZUKI-KURASAKI、Masashi OKABE、Futoshi YAMASAKI 和 Yutaka KOJIMA：“金属硫蛋白保守丝氨酸在镉结合中的作用”生化遗传学。

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)

Oikawa、Kurasaki、Kojima、Kawanishi；：“含铜金属硫蛋白引起的位点特异性 DNA 裂解的氧化和非氧化机制。”

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.

Fumitomo ODAWARA、Masaaki KURASAKI、Mika SUZUKI-KURASAKI、Shinji OIKAWA、Tadasu EMOTO、Futoshi YAMASAKI、Ana Rosa LINDE ARIAS 和 Yutaka KOJIMA：“大肠杆菌中人金属硫蛋白 2 的表达：转化细胞的镉耐受性”J.Biochem.118

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)

Odawara，Kurasaki，Suzuki-Kurasaki，Oikawa，Emoto，Yamasai，Linde，Kojima；：“转化细胞的大肠杆菌镉耐受性中人金属硫蛋白-2 的表达。”