Prevention of nickel subsulfide carcinogenesis by local administration of Mycobacterium bovis antigen in male F344/NCr rats

Abstract

This study ws designed to determine the effect of local inflammation on nickel subsulfide (Ni 3S 2) carcinogenesis. Male F344/NCr rats, 6-week-old, 20 rats/group, received a single i.m. injection of 2.5 mg of Ni 3S 2 alone or 2.5 mg of Ni 3S 2 mixed with either 0.5 mg of Mycobacterium bovis lyophilized cell walls (MB), 1 mg cortisol (CORT), or 1 mg indomethacin (IND). Two more groups of rats received i.m. Ni 3S 2 alone, as above, followed by a single s.c. dose of either 1 mg MB or 2 mg IND. The i.m. injections were made into the thigh muscles of both hind limbs; the s.c. injections were made at the neck area. The experiment was terminated at 71 weeks. The final yields of injection site sarcomas were 85% in the Ni 3S 2, 85% in the Ni 3S 2 + CORT, and 80% in the Ni 3S 2 + IND group. Only one injection site tumor (5%) was found in rats given i.m. Ni 3S 2 + MB. In contrast, the s.c. MB injection enhanced muscular carcinogenicity of Ni 3S 2 by shortening the latency and increasing the yield of tumors to 100% at week 39 ( P < 0.04vs. Ni 3S 2 alone). The s.c. treatment with IND gave similar, though statistically nonsignificant results; 100% tumor yield was reached at week 42 ( P < 0.18vs. Ni 3S 2 alone). Although local treatment with CORT or IND had no significant effect on the final tumor incidence by Ni 3S 2, it shortened the latency of tumors to 17 weeks compared with 23 weeks for Ni 3S 2 alone. MB, CORT, IND, or the injection vehicle (water) alone did not produce tumors. Local MB treatment had no significant effect on the retention of Ni 3S 2 at the injection site. The prevention of the Ni 3S 2 tumors by local MB might result from localization of numerous natural killer cells and macrophages and formation of giant cells observed at the injection site of Ni 3S 2 1–14 days post injection. These cells could immobilize the carcinogen and destroy Ni 3S 2-transformed cells.