INHIBITION OF DNA-SYNTHESIS IN CCL-39 CELLS BY IMPERMEABLE IRON CHELATORS

The synthesis of DNA in CCl 39 cells is inhibited by the presence of t he Fe2+ chelator bathophenanthroline disulfonate (BPS) when growth is stimulated by thrombin EGF plus insulin, but not by fetal calf serum. The presence of transferrin and Fe3+ in fetal calf serum can be the ba sis for lack of BPS effect with serum. The impermeable Fe3+ chelator T iron does not, by itself, inhibit growth factor induced DNA synthesis, but it induces together with BPS inhibition on fetal calf serum induc ed DNA synthesis. The combined effect of BPS and Tiron is similar to i nhibition of DNA synthesis by impermeable polyvalent DTPA which can ch elate both Fe2+ and Fe3+ but does not inhibit ribonucleotide reductase in intact cells. Ferrous iron that bind BPS can relieve the inhibitio n at stoichiometric concentration. Ferric iron also prevents the inhib ition even though it does not bind BPS. BPS does not inhibit DNA synth esis in HeLa cells. BPS reacts with iron from CCl 39 cells but,not fro m HeLa cells. Data show that iron available for impermeable external c helators is in the ferrous state, and that exogenous iron should be re duced before it reverses the inhibition.