Free radical mediated cytotoxicity of desferrioxamine

Toxic effects of desferrioxamine (DFO) upon cell growth were assayed with continuous bromodeoxyuridine (BrdU) labeling and bivariate ethidium bromide/Hoechst 33258 flow 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 G2 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.