Inhibition of intercellular communication by nickel(II): antagonistic effect of magnesium

The level of gap-junctional (cell-cell) communication was studied by the radioisotope transfer technique in NIH 3T3 cells exposed to NiSO4, MgSO4, or both salts combined. Monolayered NIH 3T3 donor cells were labeled with [3H]-uridine for 3 h and then co-cultured with non-labeled recipient NIH 3T3 cells for 3 h in the presence of 0.5-20 mM NiSO4, 1.0-100 mM MgSO4, or 5 mM NiSO4 plus 1.0-100 mM MgSO4. 12-O-tetradecanoylphorbol-13-acetate (TPA), 16-160 pM, served as a positive control. The exposed cells were fixed with 2.5% glutaraldehyde and processed for autoradiography. The cell-cell communication rate was based on the number of radioactive recipient cells in relation to the total number of recipient cells for 100 donor cells. NiSO4 disrupted cell-cell communication in a dose-related manner from 98% of the base value at 0.5 mM NiSO4 to 2% at 5 mM NiSO4. Cell viability was not affected by 0.5-5 mM NiSO4. The inhibitory action of 5 mM NiSO4 could be partially prevented by 5.0-100 mM MgSO4. However, MgSO4 did not prevent the inhibition by TPA. The results indicate that NiSO4 is capable of inhibiting cell-cell communication at concentrations that do not cause cytotoxic effects in NIH 3T3 cells during a 3-h period. In this respect NiSO4 resembles such classical tumor promoters like TPA. The antagonism by magnesium of the nickel-induced inhibition of cell-cell communication may indicate a contributory mechanism by which magnesium counteracts the carcinogenicity of nickel in vivo.