Seasonal changes in subcellular distribution of zinc, copper, cadmium and metallothionein in the liver of bank vole (Clethrionomys glareolus): a possible essential role of cadmium and metallothionein in the hepatic metabolism of copper.

1. An increase in total Zn concentration in the liver of sexually mature bank voles in spring and summer was primarily accompanied by an increase in Zn levels in the nuclear and mitochondrial-lysosomal fractions, while in immature voles in an analogous situation, Zn tended to concentrate mainly in the post-mitochondrial fraction. 2. Seasonal changes in Cu concentration in all subcellular fractions followed closely those of total hepatic Cu; however, the mitochondrial-lysosomal Cu underwent the most dramatic changes. 3. Multiple regression analysis between the concentration of metallothionein (MT) in the postmitochondrial fraction and the levels of Zn, Cu and Cd in the particular subcellular fractions showed that MT was principally induced by small amounts of Cd concentration of which in the liver ranged from 0.019 microgram/g in winter to 1.1 micrograms/g wet wt in spring. 4. The analysis revealed further that the level of MT in the post-mitochondrial fraction concurrently decreased as total hepatic Cu, as well as mitochondrial-lysosomal Cu, increased. 5. The data indicate that MT, first induced by small amounts of Cd, is involved in the hepatic metabolism of Cu in bank voles; most probably the protein sequesters free Cu ions in cytoplasm and then transfer them into the mitochondrial-lysosomal fraction.