Study on bioinorganic chemistry for the mechanism of the development of hapatitis-hepatoma in LEC rats

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We studied on copper-metallothionein (Cu-MT) induced unusually in the liver of LEC (Long-Evans Cinnamon) rats which develop spontaneous hepatic injury associated with severe jaundice and hepatoma, and obtained the following results.(1) We purified the Cu-MT and found that the protein presents in both monomer and polymer as judged by both gel-filtration and electrophoretic methods. In the partially purified protein, nevertheless, two isomers as MT-I and MT-II were detectable and they were subjected to the amino acid sequencing method, the 16 amino acid sequence from the N-terminal being determined.(2) In the partially purified Cu-MT,generation of hydroxyl radicals (・OH) was observed by ESR-spin trapping technique when the protein was reacted with hydrogen peroxide (H_2O_2) which presents in the hepatic cells. The unusual formaiton of ・OH in the Cu-MT of LEC suggests one of the causative factors for the development of the hepatic injury or hepatitis in the LEC rats.(3) To suppress the development of the hepatitis in the LEC rats, we gave a zinc complex by oral administration every day for 6 months to the rats. The data was now analyzing.(4) We analyzed both metal contents and MT levels in human liver cancers. An important finding was obtained, in which Cu-MT is induced as the human hepatoma develops. Thus the great similarity in the hepatic injury of LEC rats and human was found in terms of the induction of Cu-MT.