Metallothioneins (MTs), determined by polyacrylamide-coated capillary zone electrophoresis (CZE), coincided well with those described by enzyme-linked immunosorbent assay. By using CZE, MT isoforms 1 (MT-1) and 2 (MT-2) were well separated and determined in the liver cytosol of LEC rats and Wistar rats administered CdCl2. The total concentrations of MTs in the liver cytosol of LEC rats increased age-dependently as 1.0, 2.1, and 7.2 mg/g wet weight of the liver at the age of 5, 10, and 15 weeks, respectively, and those of Wistar rats that had received daily CdCl2 also increased with time of CdCl2 as 0.5 and 1.2 mg/g wet weight of the liver for 3 and 6 consecutive administration days, respectively. The MT-1/MT-2 ratio in the liver cytosol of LEC rats decreased age-dependently as 1.75, 1.49, and 0.76 at the age of 5, 10, and 15 weeks, respectively. In contrast, that of Wistar rats increased with time of exposure to the metal ion CdCl2 as 1.1 and 1.6 for 3 and 6 administration days, respectively. Copper accumulation in the liver of LEC rats has already been reported. The present results indicated that the mechanism of the induction of NIT synthesis differs between LEC rats, who lack ATP7B, and Wistar rats, who were given a toxic metal ion. On the basis of these results, we propose that MT-1 is related to the metabolism or detoxification of toxic metals such as Cd, and in contrast, MT-2 is responsible for the homeostasis of essential metals such as Cu. (C) 2004 Elsevier Inc. All rights reserved.