INTERACTION OF CARCINOGENIC METALS WITH TISSUES AND BODY FLUIDS . COBALT AND HORSE SERUM

During the course of induction of rhabdomyosarcomata by implanted powdered metallic cobalt in rat skeletal muscle, the metal slowly dissolves and disappears from the injection site. In attempts to find a model for the dissolution process, cobalt metal powder has been incubated aseptically with horse serum at 370 C. Under these conditions, and with air as the gas phase, the metal dissolves slowly with the formation of complexes of both small molecular components and the proteins of the serum, binding by albumin being greater than by the globulins. In these proteins, Co2+ ions appear to be bound at multiple sites, 2 of which may be free carboxyl groups and histidyl residues. Cobalt-serum, produced by incubation of the metal with horse serum for 28 days, is not only less toxic for rat myoblasts in culture than the equivalent amount of ionic Co2+ (as CoCl2), but also produces cytological changes in the myoblasts that are similar to those seen in the vicinity of the implants of metal powder in vivo. It is suggested that the cobalt-serum complex, possibly adsorbed at the surface of the myoblast, enters the cell by endocytosis. Subsequent digestion of the carrier-proteins by lysosomal proteinase(s) leads to the liberation and redistribution of the Co2+ ions. In support of this hypothesis, a partially purified preparation of a lysosomal proteinase has been shown to degrade the cobalt-serum complex. and to liberate Co2+ in a form that is freely-diffusible and which is retained by Chelex resin. © 1969, The British Empire Cancer Campaign for Research. All rights reserved.