STUDIES ON ZINC CONTENT OF CD-INDUCED THIONEIN

Liver metallothionein can be induced by the injection of a variety of metal ions, including Cd, Hg, Ag, Au, and Zn, into rats. The protein so induced contains bound zinc in addition to the other metal ion used for induction. In Cd-induced metallothionein Zn2+ was found to occupy two of the eight possible metal-binding sites in thionein prepared from animals killed at least 10 h after the injection of cadmium. Thionein isolated at earlier times contained little or no zinc. The amount of thionein formed is proportional to the dose of Cd, but the hepatic uptake of Cd precedes the mobilization of Zn by several hours. This Cd-induced mobilization of Zn is most significant in the liver. The origin of the mobilized Zn is primarily from the excretory pathway, with the diet also being a contributing factor. In mice and rats, the increased hepatic Zn arising from Cd injection can largely be accounted for by a decrease in fecal Zn. This effect of Cd-induced Zn mobilization is also observed in rats and mice made zinc deficient. The mechanism of Zn mobilization is not resolved, but may involve both an effect of cadmium on excretion and the retention of zinc in the liver caused by an elevated level of thionein. The results presented suggest a physiological role for thionein in zinc metabolism. © 1978 Academic Press, Inc.