Free Radical Mediated Cytotoxicity of Desferrioxamine

Toxic effects of desferrioxamine (DFO) upon cell growth were assayed with continuous bromodeoxyur-idine (BrdU) labeling and bivariate ethidium bromide/Hoechst 33258 Row cytometry. At 5% oxygen DFO caused a dose-dependent inhibition of cell growth. which was potentiated at 20% oxygen. and by cumene hydroperoxide but not by paraquat. An irreversible arrest in the GZ phase of the cell cycle was the cell-kinetic mechanism underlying this growth inhibition. The G2 arrest was not dependent upon the BrdU concentration in the medium, thus ruling out a direct attack of a free radical on thymidine residues. The observed cytotoxicity of DFO cautions against its use in the treatment of conditions of elevated oxidative stress.