Modification of the in vitro cytotoxicity of hydrogen peroxide by iron complexes

The effect of a range of iron chelates on the cytotoxicity of H2O2 was studied on a mammalian epithelial cell line. Iron complexes which were internalised enhanced the cytotoxicity of H2O2 measured by delayed thymidine incorporation. Iron complexed to 8-hydroxyquinoline (Fe/8-HQ) potentiated the cytotoxicity of 50 microM by 38% and Fe/dextran by 23%. Pre-exposure of cells to Fe/dextran at 4 degrees C did not result in any potentiation of H2O2-induced cytotoxicity which we ascribe to failure of the Fe/dextran to be endocytosed at low temperature. Iron complexes which are slowly taken up or remain extracellular protected the cells from H2O2-induced cytotoxicity. Thus, Fe/EDTA inhibited the cytotoxicity of 50 microM H2O2 by 33%; Fe/ADP by 80% and Fe/ATP by 88%, suggesting mutual extracellular detoxification.