Effects of manganese on carcinogenicity and metabolism of nickel subsulfide.

Nickel subsulfide, Ni3S2, alone or combined with manganese or chromium dusts, was administered i.m. to Fischer rats to study the effects of the metals upon Ni3S2 induction of sarcomas at the injection site. The incidence of sarcomas within 2 years after injection of Ni3S2 (1.2 mg) plus manganese (1.0 mg) was 7%, versus 77% in rats that received only Ni3S2 (1.2 mg), and 80% in rats that received Ni3S2 (1.2 mg) plus chromium (1.0 mg) (p less than 0.005). No local sarcomas occurred in rats that received the injection vehicle, or in rats that received manganese or chromium without Ni3S2. Admixture of manganese diminished the solubility of 63Ni3S2 in rat serum, serum ultrafiltrate, or water, in vitro. Admixture of manganese with 63Ni3S2 did not affect the mobilization or excretion of 63Ni in vivo, nor did it alter the acute pathological reactions to Ni3S2. 63Ni concentrations in ultrafiltrates of supernatant fractions of homogenates of injection sites averaged 2.8 (S. D. +/- 0.7) ng/ml at 5 to 6 months after injection of 63Ni3S2 (1.2 mg) plus manganese (1.0 mg), versus 5.4 +/- 2.0 ng/ml after injection of only 63Ni3S2 (1.2 mg) (p less than 0.02). This study demonstrates that admixture of manganese dust and Ni3S2 inhibits Ni3S2 tumorigenesis in rats, and reveals that manganese dust affects the subcellular distribution of 63Ni derived from 63Ni3S2, without influencing 63Ni kinetics as estimated by compartmental analysis.