IRON REQUIREMENT FOR CELLULAR DNA-DAMAGE AND GROWTH-INHIBITION BY HYDROGEN-PEROXIDE AND BLEOMYCIN

Studies with Euglena gracilis and HL-60 cells have assessed the need f or intracellular iron in the mechanisms of inhibition of cell growth a nd DNA damage by H2O2 and bleomycin. Cell culture media were directly depleted of iron in order to deprive cells of nutrient iron. Major poo ls of cellular iron were reduced in both cell types. Nevertheless, iro n bound in e.s.r.-observable haem protein and ribonucleotide diphospha te reductase in HL-60 cells was not decreased. In both control cell po pulations, there was a concentration-dependent reduction in proliferat ion and cell survival caused by H2O2. In comparison, the proliferation rates of both iron-deficient cell types were significantly less sensi tive to H2O2. H2O2 caused concentration-dependent single-strand breaka ge in DNA in control HL-60 and Euglena gracilis cells. Iron deficiency reduced the amount of strand breaks in HL-60 cells at each concentrat ion of H2O2 used. Single-strand breakage caused by H2O2 in Euglena gra cilis was a direct function of the concentration of iron in which the cells had been grown. Growth inhibition and both single- and double-st rand DNA damage caused by bleomycin were substantially reduced or elim inated in iron-deficient cells. Copper bleomycin behaved like metal-fr ee bleomycin when assayed for the capacity to cause DNA damage in iron -normal and iron-deficient HL-60 cells. In contrast, iron bleomycin wa s equally active under the two conditions in these cells.