Inhibitory effects of heavy metals on transcription factor Sp1

Heavy metals are expected to affect the biological activity of various metal-containing proteins, including transcriptional regulators, We studied the effects of several heavy metal ions on the DNA-binding activity of a Zn-finger transcription factor, Spl, With respect to both DNA elements through which Spl acts positively and negatively, Cd2+ inhibited DNA-binding of Sp1 at 20 mu M or higher, while the toxic effect of Zd(2+) was obvious only at more than 200 mu M. Inhibition was also apparent for Cu2+ but less remarkable for Hg2+. The inhibition by Cd2+ was relieved by the addition of Zn2+ at much lower concentrations than that of Cd2+. These results suggest that the toxic potential of heavy metals could be largely influenced by the intracellular Zn2+ concentration.