DECREASE IN BILIARY-EXCRETION OF COPPER IN LONG-EVANS CINNAMON (LEC) RATS CAUSING SPONTANEOUS HEPATITIS DUE TO A GROSS ACCUMULATION OF HEPATIC COPPER

The concentration of biliary Cu was 0.12+/-0.01 mug/ml in male LEC rat s aged 14 weeks and 0.43+/-0.09 mug/ml in Fischer rats of the same age . When copper chloride (170 mug/kg b.w. as Cu) was infused intravenous ly (iv), the concentration of biliary Cu increased to only 0.21+/-0.06 mug/ml 30 min after the infusion in LEC rats. In contrast, Fischer ra ts showed a concentration about 10 times higher (4.02+/-2.2 mug/ml) th an that before the infusion. In Fischer rats pretreated with cadmium c hloride, the biliary Cu concentration was 1.04+/-0.43 mug/ml 30 min af ter infusion of copper. Horseradish peroxidase (E.C.1.11.1.7) infused iv along with copper chloride was excreted into bile at a low level in LEC rats compared to Fischer rats. Our results suggest that the gross accumulation of hepatic Cu in the new, mutant LEC rats is due to a lo w excretion of Cu into bile and that the hepatobiliary dysfunction is related to spontaneous hepatitis.