Electron microprobe in vitro study of interaction of carcinogenic nickel compounds with tumour cells

The effect of various nickel salts on cultured rhabdomyosarcoma cells was studied. Certain of these compounds, e.g., nickel subsulfide (Ni3S2) and nickel itself, induce tumours in muscle, while others have no effect, e.g., nickel monoxide (NiO). It has been suggested that the carcinogenicity of nickel is related to its penetrating power (phagocytosis) in transformed cells. We have used electron microscopy and microanalysis to study the ultrastructure and intracellular localization of nickel in ultra-thin sections. Nickel subsulfide and nickel monoxide penetrate into cells and are concentrated in vacuoles, exhibiting a particular affinity for membrane structures. They subsequently appear to be eliminated in the extracellular medium. Colloidal nickel and iron carbonyl, on the other hand, do not penetrate cells. Various tumoral and normal cell lines were compared for their ability to phagocytose nickel subsulfide and it was found that the compound penetrated only macrophages and impregnated the membranes of polynuclear cells. These results suggest that the phagocytosis of nickel compounds is not directly related to the eventual induction of a tumour. No nuclear localization could be detected, but we did demonstrate a mechanism for the concentration and elimination of these compounds in certain tumour cells.