Nickel-induced erythrocytosis: efficacies of nickel compounds and susceptibilities of rat strains.

Five nickel compounds were adm inistered to rats by intrarenal (ir ) injec­ tion to assess the relative efficacies of the compounds for induction of erythrocytosis, based upon measurements of blood packed cell volume (PCV) at intervals from one to six months after the injection. Nickel subsul­ fide (aN i3S2) was the most potent inducer of erythrocytosis, followed by crystalline nickel monosulfide (/3NiS), nickel subselenide (aN i3Se2) and metallic nickel dust (Ni), in that order of responsivity. An ir injection of amorphous nickel monosulfide (NiS) did not induce erythrocytosis. The five nickel compounds were incubated in vitro in rat serum and the rates of dissolution of nickel were measured. In decreasing order of dissolution rates, the following relationships were observed: amorphous NiS > aN i3S2 > aN i3Se2 > /3NiS > Ni dust. Four rat strains were tested to identify the optimal strain for study of nickel-induced erythrocytosis. In decreasing order of susceptibility to erythrocytosis, the following relationships were observed: Fischer-344 > NIH Black > Wistar-Lewis > Long-Evans. This study has shown (a) that N i3S2 dust and Fischer-344 rats are the optimal nickel compound and rat strain for investigation of nickel-induced erythrocytosis; (b) that the physical form of nickel monosulfide (crystalline 3̂NiS versus amorphous NiS) has a marked effect upon the capacity to induce erythrocytosis; and(c) that in vitro rates of dissolution of nickel compounds in rat serum are not directly corre­ lated with their relative efficacies for induction of erythrocytosis in rats after ir injection. * Supported by research grants from National Institute of Environmental Health Sciences (#ES-01337) and U.S. Department of Energy (#E(11-1)3140). f Address reprint requests to F. William Sunderman, Jr., M.D., Department of Laboratory Medicine, University of Connecticut Health Center, P.O. Box G, Farmington, CT 06032.