Interaction of Carcinogenic Metals with Tissue and Body Fluids

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Abstract
In addition to cobalt, metallic nickel, cadmium and other metals (e.g. zinc and copper) dissolve when incubated with horse serum at 37°. The dissolving property of copper in serum resembles that of cobalt, its solubility being increased greatly in the presence of oxygen, whereas the solubilities of cadmium, zinc and most preparations of nickel are the same aerobically and anaerobically. In all of these “metal-sera” the cations are bound, although in different proportions, both by proteins and by small diffusible molecules. Although Co2+ ions and cobalt-serum cause limited catalytic oxidation of fresh serum, most of the oxygen uptake by suspensions of metallic cobalt in serum, or by more simple model systems, is due to absorption of oxygen by the metal powder; the consequences of this are discussed. Metallic cobalt, cadmium and nickel dissolve readily when incubated with sterile homogenates of rat muscle (and other tissues), the dissolved cations being bound predominantly by small, diffusible molecules, rather than by the protein components. Binding by small molecules, in preference to proteins, also occurs when the metals dissolve in vivo. In both the in vivo and in vitro systems, the metallic ions are not bound by a specific cation carrier, but are distributed amongst a number of components. These components have greater affinities for the dissolved metals than serum proteins and seem likely to be the normal cation carriers in vivo. As in serum, solubility in muscle homogenates is not a specific property of the carcinogenic metals as other, non-carcinogenic metals also dissolve. The specificity of the former metals, therefore, is attributed to the subsequent effects of the dissolved cations after intracellular incorporation.