Intracellular iron mediates the enhancing effect of histidine on the cellular killing and clastogenicity induced by H2O2

The enhancing effect of L-histidine on the hydrogen peroxide (H2O2) induction of micronuclei and of sister-chromatid exchanges (SCEs) as well as on its killing effect was investigated using Chinese hamster fibroblasts. L-Histidine increased cellular killing and the frequency of micronuclei but not SCEs induced by H2O2. Superoxide dismutase and mannitol did not decrease the killing effect whereas mannitol completely prevented the formation of micronuclei and of SCEs induced by H2O2 or by H2O2 plus L-histidine. When the iron-complexing agents EDTA or o-phenanthroline were present, only o-phenanthroline inhibited the killing and clastogenic effects of H2O2 or of H2O2 plus L-histidine. D-Histidine had the same effect as L-histidine, but histamine and L-urocanic acid did not. These results indicated that both the amino and the carboxylic groups of histidine are required for the enhancing effect and suggested that it depends on the formation of an intracellular histidine-iron complex able to react with H2O2 generating reactive oxygen species.