ACCUMULATION OF ORALLY GIVEN CADMIUM IN LONG-EVANS CINNAMON (LEC) RATS WITH AN INHERENTLY ABNORMAL COPPER-METABOLISM

An inherent defect of biliary Cu excretion and subsequent Cu depositio n in the liver have been found in Long-Evans Cinnamon (LEC) rats, whic h are promising models of Wilson disease. LEC and Fischer rats were gi ven water containing Cd (CdCl2) at a level of 5 ppm for 30 days. Regar dless of drinking Cd water, LEC rats showed a very high concentration of Cu (200 to 250 mu g/g) and Cu-metallothionein (Cu-MT) (18 mg/g) in the liver. There was no difference of Cd accumulation in the liver bet ween the two strains exposed to Cd (2.6 and 2.7 mu g/g in the Fischer and LEC groups, respectively). However, the renal Cd concentration was slightly but significantly higher in LEC rats (3.5 mu g/g) than in Fi scher rats (2.0 mu g/g). The ratio of renal Cd contents to the sum of renal and hepatic Cd contents was significantly higher in LEC rats (0. 25) than in Fischer rats (0.15). The serum Cd concentration in Cd-trea ted LEC rats increased threefold compared to Cd-treated Fischer rats. It seems likely that Cd from the liver is transported into the kidney in the form of Cd, Cu-MT. There was no difference in uptake of Cd in t he hepatic MT fraction between the two strains. Although biliary Cu ex cretion in LEC rats was significantly lower than that in Fischer rats, reduced excretion of Cd into bile was not found in LEC rats. The gros s amounts of Cu and Cu-MT influenced the accumulation of Cd in the kid ney rather than in the liver when Cd was given orally at a low level t o LEC rats. Our results suggest that Cu and Cd do not share the same s ites of hepatobiliary excretion in rats, although the main route of th eir excretion is via bile.