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

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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.