ENHANCED SYNTHESIS OF METALLOTHIONEIN AS A POSSIBLE CAUSE OF ABNORMALCOPPER ACCUMULATION IN LEC RATS

Long-Evans rats with a cinnamon-like coat color (LEC) is an inbred str ain accumulating copper (Cu) in the liver abnormally and showing spont aneous hepatitis and hepatoma. The present study was intended to clari fy how Cu accumulates in the LEC rat liver. For this purpose, the dist ribution profiles of Cu and zinc (Zn) and the inducibility of metallot hionein (MT) synthesis were examined in the liver between Cu-loaded Lo ng Evans agouti (LEA, the original strain of LEC) rats and were compar ed with those in control LEC rats. LEA rats (female, five weeks old) w ere injected subcutaneously with CuCl2 daily at a dose of 3 mg Cu/kg b ody weight for 2, 4, 6, and 9 days. The concentration of Cu (124 mu g/ g) accumulated in the LEA rat liver after four injections was comparab le to that in control LEC rats. Only 20% of Cu in the liver of LEA rat s was recovered in the supernatant fraction in the form of MT, while C u in the LEC rat liver (113 mu g/g) was recovered mostly in the supern atant fraction, and was bound to MT. Although the increased concentrat ion of Cu in the LEA rat liver was further elevated after additional i njections of Cu, the amount of MT did not increase further. The MT mRN A content in the LEA rat liver remained lower than that of LEC rats ev en after further injections of Cu. Therefore, the present results sugg est that LEC rats can accumulate Cu at a high concentration in the liv er because of their extremely high inducibility of MT.