The requirement for Zn++ in DNA replication by phytohemagglutinin-stimulated human lymphocytes was studied. When 6 µM o-phenanthroline, a chelator with a high affinity for Zn++, is added to cultures of stimulated lymphocytes a nearly complete inhibition of thymidine incorporation results within a few hours. In contrast, the incorporation of uridine is only slightly reduced and the incorporation of leucine is unaffected. m-Phenanthroline, a nonchelating analogue, does not alter the rate of thymidine incorporation even when present in 10-fold greater amounts than o-phenanthroline. The inhibition of thymidine incorporation by o-phenanthroline could be entirely reversed by the addition of Zn++ to the cultures, or could be prevented by the prior addition of either Zn++ or Ni++. All other divalent cations tested were incapable of reversing the o-phenanthroline inhibition of thymidine incorporation.

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