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Nickel--magnesium interactions in carcinogenesis: dose effects and involvement of natural killer cells
Abstract:
The effects of magnesium carbonate (MgCarb) on carcinogenesis and natural killer (NK) cell modulation by nickel subsulfide (Ni3S2) were studied. Male Fischer F344/NCr rats, 50-90 g body wt, 20 rats per group, received single i.m. injections into both thigh muscles of 2.5 mg Ni3S2 alone or combined with different proportions of MgCarb; the Mg/Ni molar ratio ranged from 0.25 to 4.0. Control rats received i.m. injections of normal saline or magnesium acetate (MgAcet), or s.c. MgCarb at a site distant from Ni3S2. The animals were observed over 79 weeks for the development of tumors. The NK cell activity was determined over the first 3 weeks of the experiment in separate groups of rats treated as above, with the use of the 51Cr/YAC-1 release assay for blood and spleen cells and the peroxidase localization of Ox-8-immunoreactive lymphocytes at the injection site. I.m. administration of MgCarb mixed with Ni3S2 up to the Mg/Ni molar ratio of 1.0 inhibited the carcinogenicity of Ni3S2 in a dose-related manner; final incidence of sarcomas decreased from 100 to 55% and the appearance of first tumors was delayed from 25 to 39 weeks. Higher doses of MgCarb did not exert further effect. Distant s.c. injection of MgCarb or local i.m. application of MgAcet did not change the carcinogenic potency of i.m. Ni3S2. MgCarb or saline alone did not produce any tumors. I.m. Ni3S2 had no significant influence on the activity of NK cells in blood and spleen, while i.m. MgCarb alone did not affect the NK activity in blood but doubled it transiently in the spleen 24 h after injection. In the injected muscle, Ox-8-positive cells became abundant around MgCarb but could not be found close to Ni3S2. This inhibitory effect of Ni3S2 was partially reversed by MgCarb. Also, numerous multinucleated giant cells infiltrated the sites of injection of MgCarb alone and MgCarb + Ni3S2 but not Ni3S2 alone. The results indicate a dose-dependent and strictly local character of the inhibition by MgCarb of Ni3S2 carcinogenesis, as well as a possible involvement of NK and phagocytic cells in this inhibition.
Insights
Magnesium carbonate (MgCarb) locally inhibits nickel subsulfide (Ni3S2) carcinogenicity in rats, reducing tumor incidence and delaying onset. This effect involves natural killer (NK) cells and phagocytic cells, highlighting MgCarb
Area of Science:
- Toxicology
- Carcinogenesis
- Immunology
Background:
- Nickel subsulfide (Ni3S2) is a known carcinogen.
- The role of magnesium carbonate (MgCarb) in modulating carcinogenesis and immune responses is not fully understood.
Purpose of the Study:
- To investigate the effects of MgCarb on Ni3S2-induced carcinogenesis.
- To examine the impact of MgCarb on natural killer (NK) cell activity in the presence of Ni3S2.
Main Methods:
- Rats were injected with Ni3S2 alone or in combination with varying ratios of MgCarb.
- Tumor development was monitored over 79 weeks.
- NK cell activity was assessed using chromium-51 (51Cr) release assays and immunohistochemistry.
Main Results:
- MgCarb inhibited Ni3S2 carcinogenicity in a dose-dependent and local manner, reducing sarcoma incidence from 100% to 55% and delaying tumor appearance.
- Ni3S2 alone did not significantly affect NK cell activity in blood or spleen, but MgCarb alone transiently increased spleen NK activity.
- MgCarb modulated the inflammatory response at the injection site, increasing Ox-8-positive cells and multinucleated giant cells, suggesting involvement of immune cells.
Conclusions:
- MgCarb exhibits a dose-dependent, local inhibitory effect on Ni3S2 carcinogenesis.
- The inhibition mechanism may involve the modulation of NK cells and phagocytic cells at the local injection site.