BINDING OF CU TO METALLOTHIONEIN IN TISSUES OF THE LEC RAT WITH INHERITED ABNORMAL COPPER ACCUMULATION

Long-Evans Cinnamon (LEG) rats aged 16 +/- 4 weeks with histopathologi cal alterations of liver and kidney, exhibited elevated Cu levels in l iver, kidney and spleen which were 52, 27 and 5 times higher than thos e of the respective tissues of age-matched Wistar rats. About 61% of h epatic and about 38% of renal Cu was recovered in the cytosolic fracti on. Metallothionein (MT) levels were found to correlate with the cytos olic Cu concentrations in liver and kidney, According to differential MT analysis, about 68 and 82% of hepatic and renal MT was loaded with Cu. The portion of MT which binds Cu was negatively correlated with th e ratio of cytosolic Zn/Cu in all organs investigated. Despite high MT levels and the high percentage of Cu binding to MT, particularly in l iver and kidney, considerable amounts of Cu remained unbound to MT. Th is non-MT bound Cu showed good correlation with the total cytosolic Cu content, and might play a crucial role in the pathogenesis of Cu toxi cosis.