DNA strand scission by the nephrotoxin [2,2′-bipyridine]-3,3′,4,4′-tetrol-1,1′-dioxide and related compounds in the presence of iron

Author： Cantin-Esnault Danielle Oubrahim Hammou Richard Jean-Michel

Publisher： Informa Healthcare

ISSN： 1071-5762

Source： Free Radical Research, Vol.33, Iss.2, 2000-01, pp. : 129-137

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Abstract

The capacity of non-illuminated nephrotoxin orellanine ([2,2′-bipyridine]-3,3′,4,4′-tetrol-1,1′-dioxide) to induce DNA damage in the presence of ferrous iron and dioxygen has been evaluated. Maximal single-strand breaks in plasmid DNA were obtained with a metal to ligand ratio 1:3. Instantaneous oxidation of Fe 2+ in presence of orellanine under air was responsible for oxy-radical production concomitant to a stable ferric complex Fe(III)Or 3 formation, leading to oxidative DNA breakage at physiological pH. DNA damage was lowered in the presence of SOD and catalase or DMSO, indicating a set of reactions that leads to oxyradical generation. Iron chelators such as DTPA and EDTA had no protecting effect, Desferal slightly protected. GSH acted as an oxy-radical scavenger, whereas cysteine induced stronger damage. Closely related bipyridine compounds were also studied in presence of Fe 2+ and O 2 using a combination of spin-trapping and DNA-nicking experiments, none of which were able to chelate iron and induce damage at pH 7. Both catecholic moieties and aminoxide groups are required for observing breakage at physiological pH.