In vitro effects of metal ions on cellular metabolism and the correlation between these effects and the uptake of the ions.
The effects of Ag+1, Au+3, Cd+2, Cu+2, Ga+3, In+3, Ni+2, Pd+2, and Zn+2 on DNA synthesis, protein synthesis, succinic dehydrogenase activity, and total cellular protein of mammalian fibroblasts were measured for exposures less than 12 h. The rates at which these cellular functions responded to metal ion exposure were compared and related to the uptake rate of the ions into the cells. These rates of response were significantly different: DNA synthesis decreased the fastest, followed by protein synthesis, succinic dehydrogenase activity, and total protein. This order of response was similar for most metal ions. At 4 h, the rate of uptake of the metal ions correlated most closely with depression of succinic dehydrogenase activity, whereas at 8 h, the uptake correlated most closely with depression of protein synthesis. The similar response of cells to all metal ions may imply that these ions act on cells by similar mechanisms. The rates of uptake of Ag+1, Cu+2, and Zn+2 were sufficiently fast that in vivo exposures of tissues to these metals for periods less than 12 h would be capable of disrupting cellular metabolism.