The in vitro effects of metal cations on eukaryotic cell metabolism

The in vitro cytotoxicity of nine metal cations common in dental casting alloys was evaluated using Balb/c 3T3 fibroblasts and four toxicity parameters: total protein production, 3H-leucine incorporation, 3H-thymidine incorporation, and MTT-formazan production. Concentrations causing 50% toxicity compared to controls (TC50's) and reversibility of these effects were determined. The range of potency of the metal cations was 2-3 orders of magnitude, with Cd2+ showing the greatest potency and In3+ showing the least. Potency did not correlate with atomic weight for these metals. For each metal cation, the TC50's of the various toxicity parameters were similar in most cases. However, several cations (Cu2+, Ga3+) showed greater potency with 3H-thymidine incorporation. Reversibility of the toxic effects was observed for all cations; the effects generally became irreversible at concentrations in the range of the TC50 value for each cation. Several stimulatory effects were seen. Small but statistically significant stimulations were observed after 24 h of metal exposure for Ag1+, Au4+, Cu2+, Ga3+, and Ni2+. Residual stimulations 24 h after removal of the metal cations were observed for Au4+, Cd2+, Ni2+, and Zn2+. Stimulations always occurred at concentrations below the TC50 concentrations. This study should be useful in evaluating the potential cytotoxic effects of metal cations released from dental alloys.