Effects of ethylenediaminetetraacetic acid and 1,10-phenanthroline on cell proliferation and DNA synthesis of Ehrlich ascites cells.

The interactions of ethylenediaminetetraacetic acid (EDTA) and 1,10-phenanthroline with Ehrlich cells have been studied. Both compounds inhibit proliferation of cells in culture. After long-term incubation of cells with these metal-chelating agents under conditions in which cell viability is not impaired but proliferation is retarded, the rate of DNA synthesis of EDTA-exposed cells is the same as that of untreated controls, whereas the rate of DNA synthesis of 1,10-phenanthroline-exposed cells is markedly reduced. This is in agreement with the inhibition of short-term DNA synthesis by similar concentrations of 1,10-phenanthroline as well as the lack of effect of EDTA upon DNA synthesis. The rapid direct effect of 1,10-phenanthroline upon cells in S phase is consistent with the finding that a large fraction of this metal-binding ligand but not of EDTA can be readily taken up by cells. These results differ in significant ways from the response of Ehrlich cells in vivo to host zinc deficiency. Finally, titration of ligand-treated cell cultures with zinc reverses the inhibition of DNA synthesis and cell proliferation in a linear manner, suggesting that the removal of ligand by complexation and the addition of a previous unavailable essential metal is occurring in these reactions.