Cadmium, copper, and zinc distribution in blood of rats after long-term cadmium administration

Cd, Cu, and Zn were determined in plasma and blood cells of rats given daily sc injections of 0.5 mg Cd per kilogram of body weight for 4, 8, and 15 wk. The distribution of these metals in the plasma was also examined by Sephadex G-75 chromatography. In the whole blood Cd increased continuously and reached 1.5 micrograms/ml at 15 wk. Plasma Cd was less than 2% of the total Cd in blood at first and increased to 7.8% in the last week. A significant portion of plasma Cd was found in the metallothionein fraction at 4 wk. The Cd in this fraction increased to more than 50% of the plasma Cd after the 15-wk exposure. The rest of the plasma Cd was distributed in high-molecular-weight protein fractions. Blood Cu was up to 1.3-1.4 micrograms/ml (about twice the value for controls) from 4 to 8 wk, but diminished to about a half the control value at 15 wk. These changes were greater in the plasma and parallel to the Cu contents of the ceruloplasmin fraction. A small amount of plasma Cu was found in the metallothionein fraction at 4 wk. In this fraction Cu increased to about 8% of the plasma Cu at the last week. Blood Zn remained almost unchanged at first but decreased in the last week. Most of the plasma Zn was recovered from high-molecular-weight protein fractions, but not from the metallothionein fraction. Metallothionein in the plasma contained more Cu than Cd. Plasma concentrations of Cd bound to this protein were 0.008, 0.029, and 0.104 micrograms/ml, and the Cu/Cd molar ratios were 9.9, 3.4, and 1.1 at 4, 8, and 15 wk, respectively.