INDUCTION OF RENAL CANCERS IN RATS BY INTRA-RENAL INJECTION OF NICKEL SUBSULFIDE

Abstract

The carcinogenicity of nickel subsulfide (.alpha.Ni3S2) was studied following intrarenal (i.r.) injection in rats. Within 100 wk after i.r. injection of 5 mg of .alpha.Ni3S2, renal cancers were found in 64% of Wistar-Lewis rats, 50% of NIH Black rats, 28% of Fischer rats and O% of Long-Evans rats. These findings demonstrate significant differences in susceptibilities of the 4 rat strains to .alpha.Ni3S2-induction of renal cancers. No renal cancers were found in male Fischer rats that received i.r. injection of .alpha.Ni3S2 in dosage of 0.6, 1.2 or 2.5 mg. In male Fischer rats that recieved i.r. injection of .alpha.Ni3S2 in dosages of 5 or 10 mg, the incidences of renal cancers were 28 and 75%, respectively. A dose-response relationship for .alpha.Ni3S2-induction of renal cancers was demonstrated. In male Fischer rats that received i.r. injection of 10 mg of .alpha.Ni3S2 combined with 6.9 mg of Mn dust, the incidence of renal cancers was 32%, which differed significantly from the corresponding incidences of 75 and 0% in rats that received i.r. injections of .alpha.Ni3S2 (10 mg) or Mn dust (6.9 mg). .alpha.-Ni3S2-induction of renal cancers is apparently inhibited by simultaneous administration of Mn. All 54 renal tumors found in this study were malignant and distant metastases were present in 69% of tumor-bearing rats. The histogenesis of .alpha.Ni3S2-induced renal tumors from epithelial or mesenchymal progenitor cells could not be definitely established.