Intracellular distribution of radiogold. Localization to large granule membranes

The distribution of gold in Kupffer cells and in subcellular fractions of rat liver was studied at intervals following intraperitoneal injection of 195Au sodium thiomalate (Myochrysine). Kupffer cells, isolated by digestion of whole liver with Pronase, had radioactive gold counts per milligram of protein that were twice the counts in the digested liver supernatant. After fractionation of liver cells by differential centrifugation, radiogold was found predominantly in the nuclear, mitochondrial, and lysosomal fractions. When the distribution of isotope was related to the protein content, the highest gold concentration was found in the lysosomal fraction, where it was 28 times that in the soluble fraction. Most radiogold was nondialyzable, probably a result of binding to larger intracellular compounds. Approximately 95% of the nondialyzable gold was in the organelle membrane of attached to membrane-adsorbed material, as determined by treatment of dialyzed mitochondrial and lysosomal fractions with Triton X-100. These data suggest that the intracellular locus of gold action may reside in organelle membranes.