The chemical form of cadmium in subcellular fractions following cadmium exposure.

Wistar rats were given drinking water containing 250 ppm Cd for 12 months. After excision of the kidney and liver, the organs were subfractionated into nuclear, mitochondrial, microsomal and cytosol fractions, and the chemical forms of Cd in the subcellular fractions were examined. Although approximately 90% of the total Cd was present in the cytosol, in the form of metallothionein, 3-5% was also present in the mitochondrial fraction and 5-7% in the microsomal fraction from both organs. By Sephadex G-75 gel filtration, after solubilizing the particulate fractions with sodium deoxycholate, approximately 89% of Cd in the microsomal fraction and 94% in the mitochondrial fraction eluted with the same retention time as that of metallothionein in both liver and kidney, while the remainder was found in a high molecular weight protein fraction. The Cd that eluted with the high molecular protein fraction may be involved in dysfunction in subcellular organelles. For estimating the toxicity of Cd associated with the high molecular weight fraction, rat liver microsomes and CdCl2 were mixed with 1% of sodium deoxycholate and the protein-Cd complex produced was isolated by eluting with Sephadex G-75. This complex had a strong toxicity toward the alcohol dehydrogenase activity (SH-enzyme), and the Ki values of the Cd-protein complexes decreased with increased amount of Cd bound to the microsomal protein fraction. The above results suggest that loosely bound Cd increased in the case of higher Cd/protein and plays a toxic role in the living cells.