Effects of manganese compounds on carcinogenicity of nickel subsulfide in rats.

The effects of manganese compounds upon the carcinogenicity of alpha Ni3S2 were tested in male Fischer rats. In Experiment I, rats were given i.m. injections of alpha Ni3S2 (2.5 mg) and Mn dust (2.0 mg), singly or in combination. By 100 weeks, sarcomas occurred at the injection site in 0 of 24 rats in the vehicle control group, in 0 of 24 rats that received Mn dust alone, and in 23 of 24 rats that received alpha Ni3S2 alone. Combined administration of alpha Ni3S2 plus Mn dust as a single i.m. injection resulted in sarcomas in 14 of 23 rats (p less than 0.05 versus alpha Ni3S2 alone). In rats that received injections of alpha Ni3S2 in one thigh and Mn dust in the opposite thigh, the sarcoma incidence at the site of alpha Ni3S2 injection was 24 of 24 rats. In Experiment II, rats were given i.m. injections of alpha Ni3S2 (1.2 mg) and Mn compounds (MnS, Mn2O3, MnO2 or MN2(CO)10, in dosages equivalent to 1.0 mg of Mn), singly or in combination. No sarcomas occurred at the injection site in rats that received the vehicle or any of the manganese compounds alone. Sarcomas occurred in 13 of 27 rats that received alpha Ni3S2 alone; this sarcoma incidence was not reduced by admixture of any of the Mn compounds. The median tumor latent period and the median survival period were significantly longer (p less than 0.05) in rats that received MnS plus alpha Ni3S2, compared with rats that received alpha Ni3S2 alone, suggesting that MnS may have weak anticarcinogenic effect. These experiments demonstrate that inhibition of alpha Ni3S2-carcinogenesis by Mn dust is a local rather than a systemic effect, and that, with the possible exception of MnS, the other manganese compounds that were tested are ineffective as inhibitors of alpha Ni3S2-carcinogenesis.