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

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。

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.