Physicochemical and biological attributes of nickel compounds in relationship to carcinogenic activities.

Nickel compounds that possess similar elemental compositions but vary in physicochemical properties can elicit markedly different biological effects. The crystalline nickel sulfides and oxides that slowly dissolve in body fluids and readily enter cells by phagocytosis tend to be most active in producing morphological transformation of SHE cells in vitro and stimulating erythrocytosis and carcinogenesis following ir administration to rats. The capacities of particulate nickel compounds to induce erythropoietin-mediated erythrocytosis in rats are closely correlated with their carcinogenic activities; hence erythrocytosis stimulation can serve as a screening test for carcinogenicity. Although water-soluble nickel salts have not been shown to initiate carcinogenesis in rodents, the soluble nickel salts are evidently effective as cancer promotors following initiation of tumorigenesis by aromatic hydrocarbons and nitrosoamines. Growing evidence suggests that the Ni(III)/Ni(II) redox-couple facilitates oxygen free-radical reactions, which may represent one of the molecular mechanisms for genotoxicity and carcinogenicity of nickel compounds.