New roles for quin2: powerful transition-metal ion chelator that inhibits copper-, but potentiates iron-driven, Fenton-type reactions.
The objective of this study was to investigate whether quin2, through its metal chelating properties, could affect copper- or iron-driven Fenton reactions. Chelation of ferric ion with quin2 uniformly strongly enhanced the formation of oxidizing species, detected with the DMSO and deoxyribose assays, both by H2O2 and a mixture of superoxide/hydrogen peroxide produced by hypoxanthine/xanthine oxidase. Fe(3+)-EDTA gave the same effects, but lacked reactivity with bolus H2O2 as detected with the DMSO assay. Whereas the formation of oxidizing species with Fe(3+)-EDTA and ferric ions alone were strongly inhibited by superoxide dismutase both in the bolus H2O2 and hypoxanthine/xanthine oxidase systems, such formation in the presence of Fe(3+)-quin2 either did not decrease or decreased only moderately. Fe(3+)-quin2 also strongly enhanced plasmid DNA strand breakage in the presence of H2O2. Our findings suggest that quin2 as chelator of ferric ion may be a more powerful enhancer of oxidant formation than other chelators so far tested. The formation of oxidizing species from copper ions and bolus H2O2 was found to be fundamentally dependent on the choice of buffer system. We could only detect significant amounts of oxidants in both assays in Hepes buffer, but not in the phosphate, cacodylate or unbuffered systems, which all gave low reactivity in the DMSO assay compared to the deoxyribose assay. Quin2 chelation of cupric ion effectively inhibited the formation of oxidants as well as plasmid DNA strand breakage.(ABSTRACT TRUNCATED AT 250 WORDS)
Sandström
B E
BE
Division of Ionizing Radiation and Fallout, National Defence Research Establishment, Umeå, Sweden.
Granström
M
M
Marklund
S L
SL
D000634:Aminoquinolines / Q000633:toxicity; D002614:Chelating Agents; D002712:Chlorides; D003300:Copper / Q000633:toxicity; D019327:Copper Sulfate; D004249:DNA Damage; D003855:Deoxyribose; D004121:Dimethyl Sulfoxide; D004926:Escherichia coli; D005290:Ferric Compounds / Q000633:toxicity; D005456:Fluorescent Dyes; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007501:Iron; D007700:Kinetics; D010957:Plasmids / Q000187:drug effects
D000634:Aminoquinolines; D002614:Chelating Agents; D002712:Chlorides; C045076:Fenton's reagent; D005290:Ferric Compounds; D005456:Fluorescent Dyes; D003855:Deoxyribose; D003300:Copper; D006861:Hydrogen Peroxide; D007501:Iron; D019327:Copper Sulfate; C035739:Quin2; C024555:ferric chloride; D004121:Dimethyl Sulfoxide