COPPER-METABOLISM AT 2 STAGES IN THE ONSET OF SPONTANEOUS HEPATITIS IN NEW MUTANT LONG-EVANS CINNAMON (LEC) RATS - INDUCTION OF HEPATIC COPPER-METALLOTHIONEIN AND ITS LEAKAGE FROM HEPATOCYTES

There was no difference in the activities of marker enzymes for hepatic dysfunction between Fischer and 80-day-old LEC (LEC-80) rat groups. In a 130-day-old LEC (LEC-130) rat group, these activities were increased greatly. However, a Cu enzyme, ferroxidase (E.C. 1.16.3.1), commonly called ceruloplasmin, showed markedly low activities in both LEC groups. Metallothionein (MT), probably Cu-MT, leaked into the blood even in the LEC-80 group (69.3 +/- 7.7 ng/ml serum as MT-I). The leakage was accelerated much more in the LEC-130 group (2,415.0 +/- 2,133.0 ng/ml serum as MT-I). Both LEC groups showed a high concentration of hepatic Cu. The LEC-130 group showed a significantly high concentration of Ca and a low concentration of Mg in the liver compared to those in the liver in the Fischer group. In LEC rats, most hepatic Cu was recovered in the MT fraction and, furthermore, the MT concentration was very high. These results suggest that LEC rats have an inherently peculiar Cu metabolism that changes progressively with age, resulting in Cu toxicosis, namely, the onset of hepatitis.