Effects of heavy metal ions on intercellular communication in Syrian hamster embryo cells

Several heavy metal salts [NiSO4, Cd(CH3COO)2, Pb(CH3COO)2, K2CrO4, CrCl3] were examined for their effects on intercellular communication in primary Syrian hamster embryo (SHE) cells and in the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-sensitive SHE cell line BPNi. Two exposure regimes were used: the standard regime where the exposure occurred after the cells had grown to confluence; and a non-standard regime where a high number of cells were seeded in a medium containing the metal salts. None of the chemicals were potent inhibitors of communication, i.e. effects were only found at concentrations that were non-compatible with long-term survival of the cells. NiSO4 inhibited communication in both regimes and in both cell types, but the effect was more pronounced for BPNi cells in the non-standard regime. K2CrO4 inhibited communication in the non-standard regime in both cell types, but significantly increased communication in the standard regime in BPNi cells. Similar effects were not found with CrCl3 or KCl. Thus, they were due to the properties of the CrO4(2-) ion. K2CrO4 upregulated communication in TPA-exposed BPNi cells. A high concentration of SO4(2-) did not influence the K2CrO4 inhibition in the non-standard regime, but it significantly inhibited the K2CrO4-induced increase in communication in the standard regime in BPNi cells. This suggests that K2CrO4 acts through two different mechanisms in the two exposure regimes. The CrO4(2-)-sensitive site that causes enhancement of communication in the standard regime is probably intracellular, while the site causing CrO4(2-) inhibition in the formation of gap junctional communication in the non-standard regime is most likely to be extracellular.