To elucidate the initial steps of carcinogenesis by nickel subsulfide, the mechanisms of dissolution of alpha-Ni3S2 were studied by incubating alpha-Ni3S2 dust in (a) water, (b) rat serum, and (c) rat serum ultrafiltrate. The sediments that remained following incubation of alpha-Ni3S2 in the 3 media for 2 weeks were examined by X-ray diffractometry. The rates of solubilization of 63Ni from alpha-63Ni3S2 during incubation in the 3 media were measured by liquid scintillation counting. These studies showed that solubilization of Ni(II) from alpha-Ni3S2 in rat serum requires the presence of O2 and involves three reactions: [I] 2 alpha-Ni3S2 + O2 + 2H2O leads to 4 beta-NiS + 2Ni(OH)2; [ii] beta-NiS + 202 leads to Ni2+ + SO4(2-); and [III] Ni2+ & Ni(OH)2 + serum ligands [albumin & amino acids] leads to soluble Ni(II)-complexes. The rate of solubilization of 63Ni from alpha-63Ni3S2 was initially more rapid in rat serum than in serum ultrafiltrate and much more rapid than in water. After 2 days of incubation the rates of dissolution of alpha-63Ni3S2 in the 3 media became progressively retarded, probably owing to deposition of insoluble surface coatings of beta-63Nis and 63Ni(OH)2 on the alpha-63Ni3S2 particles.
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