DNA Single Strand Breakage by H₂O₂and Ferric or Cupric Ions: Its Modulation by Histidine

Abstract

The role of histidine on DNA breakage induced by hydrogen peroxide (H2O2) and ferric ions or by H2O2 and cupric ions was studied on purified DNA. L-histidine slightly reduced DNA breakage by H2O2 and Fe3+ but greatly inhibited DNA breakage by H2O2 and Cu2+. However, only when histidine was present, the addition of EDTA to H2O2 and Fe3+ exhibited a bimodal dose response curve depending on the chelator metal ratio. The enhancing effect of histidine on the rate of DNA degradation by H2O2 was maximal at a chelator metal ratio between 0.2 and 0.5, and was specific for iron. When D-histidine replaced L-histidine, the same pattern of EDTA dose response curve was observed. Superoxide dismutase greatly inhibited the rate of DNA degradation induced by H2O2, Fe3+, EDTA and L-histidine involving the superoxide radical. These studies suggest that the enhancing effect of histidine on the rate of DNA degradation by H2O2 and Fe3+ is mediated by an oxidant which could be a ferrous-dioxygen-ferric chelate complex or a chelate-ferryl ion.