Influence of physicochemical properties, methods of preparation and purity of nickel compounds on their biological effects.

Epidemiological investigations carried out on workers in certain areas of nickel refineries have shown that a relationship exists between exposure to certain nickel compounds and cancer of the nasal passages and the lungs. Animal experiments have shown that nickel compounds cause tumours, the carcinogenicity being greater the lower the solubility of the compound in water (solubility less than 10(-3) mole/l). Amorphous nickel monosulfide (solubility less than 10(-5) mole/l) is an exception to this rule. It has been demonstrated by X-ray photoelectron spectroscopy that the surface properties of crystalline nickel monosulfide differ from those of the amorphous variety, in that amorphous nickel monosulfide has a positive surface charge while that of the crystalline sulfide is negative. It would seem that, as in the case of asbestos, a negative surface charge is an important factor in the ability to transform cells. Carcinogens are electrophiles. The differences in the behaviour of nickel compounds can be explained by the theory of hard and soft acids and bases. These considerations and the differences in the rates of cell transformation show the importance of the methods used to prepare the compounds (precipitation from solution, reaction between the elements in vacuo, solid-gas reactions) which very often lead to the formation of non-stoichiometric phases (hexagonal nickel monosulfide, nickel monoxide, high-temperature nickel subsulfide) having completely different thermodynamic, electrical, magnetic and surface properties and specific surface areas. Phase and Eh pH diagrams as well as those of Ellingham (1948) for the nickel oxides and sulfides show that certain phases are unstable and that it is important to specify precisely the conditions governing storage, grinding, handling and injection. A precise knowledge is required of the chemical composition of ores, mattes and dusts, since certain elements and compounds, e.g., manganese, even when present only in trace amounts, can act either as promoters or inhibitors in biological processes. This paper therefore demonstrates the importance of specifying the methods of preparation and determining the physico-chemical properties and purity of nickel compounds before biological studies are undertaken.

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.