Effect of silver, copper, mercury, and nickel ions on cellular proliferation during extended, low-dose exposures

Previous studies have demonstrated and quantified the cytotoxicity of metal ions in vitro, but the data from these reports have been limited to short- term exposures of metal ions to cells (24-72 h). Yet, the longer-term, low- dose effects of metal ions are most relevant to the clinical use of dental and other biomedical alloys. Thus, the purpose of the current study was to assess longer-term effects of ions of silver, copper, mercury, and nickel - four metal ions known to be released from dental alloys - on monocytes. TH P-1 human monocytes were exposed to the metal ions for up to 4 weeks. Conce ntrations of the metal ions were 1-10% of those known to cause cytotoxicity with 24-h exposures. Cellular proliferation and cellular viability were me asured weekly. Ag1+ and Hg2+ did not alter the percentage of non-viable cel ls, but Cu2+ and Ni2+ increased the nonviable component as a function of me tal concentration. These effects were cumulative over the 4 weeks only for Ni2+. All metal ions caused a signficant reduction in cellular proliferatio n, but the pattern of the effect was unique to each metal ion, and the effe cts were often not evident until 3 or 4 weeks of exposure. The results of t he current study indicate that metal ions released from metallic biomateria ls may have adverse biological effects at concentrations lower than previou sly reported. (C) 2000 John Wiley & Sons, Inc.