DNA single strand breakage by H2O2 and ferric or cupric ions: its modulation by histidine.
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.
Tachon
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Laboratoires de Recherche Fondamentale de L'Oreal, Aulney-sous-Bois, France.
D003300:Copper / Q000633:toxicity*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004278:DNA, Superhelical; D004279:DNA, Viral; D004492:Edetic Acid / Q000494:pharmacology; D005290:Ferric Compounds / Q000633:toxicity*; D006639:Histidine; D006861:Hydrogen Peroxide / Q000633:toxicity*; D066298:In Vitro Techniques; D007700:Kinetics; D013482:Superoxide Dismutase / Q000378:metabolism
D004278:DNA, Superhelical; D004279:DNA, Viral; D005290:Ferric Compounds; D006639:Histidine; D003300:Copper; D004247:DNA; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase