Lewandowska, HannaStepkowski, Tomasz M.Sadło, JarosławWójciuk, Grzegorz P.Wójciuk, Karolina E.Rodger, AlisonKruszewski, Marcin2026-01-012026-01-010968-0896PubMed:23063520ORCID:/0000-0002-7111-3024/work/162949272https://hdl.handle.net/1885/733800484Formation of dinitrosyl iron complexes (DNICs) was observed in a wide spectrum of pathophysiological conditions associated with overproduction of NO. To gain insight into the possible genotoxic effects of DNIC, we examined the interaction of histidinyl dinitrosyl iron complexes (HIS-DNIC) with DNA by means of circular dichroism. Formation of DNIC was monitored by EPR and FT/IR spectroscopy. Vibrational bands for aquated HIS-DNIC are reported. Dichroism results indicate that HIS-DNIC changes the conformation of the DNA in a dose-dependent manner in 10 mM phosphate buffer (pH 6). Increase of the buffer pH or ionic strength decreased the effect. Comparison of HIS-DNIC DNA interaction with the effect of hydrated Fe2+ ion revealed many similarities. The importance of iron ions in HIS-DNIC induced genotoxicity is confirmed by plasmid nicking assay. Treatment of pUC19 plasmid with 1 μM HIS-DNIC did not affect the plasmid supercoiling. Higher concentrations of HIS-DNIC induced single strand breaks. The effect was completely abrogated by addition of deferoxamine, a specific strong iron chelator. Our data reveal that formation of HIS-DNIC does not prevent DNA from iron-induced damage and imply that there is no direct interrelationship between iron-NO coordination and their mutual toxicity modulation.The authors declare that there are no conflicts of interest. This work was supported by a statutory Grant for INCT (H.L., T.S., G.P.W., K.E.W.), a statutory Grant for IRH (M.K.), Marie Curie Fellowship No.: HPMT-CT-2001-00366 (H.L.) and Polish Ministry of Science and Higher Education Grant No.: N N204 0778 33 (J.S. and M.K.).7enCircular dichroismDNAElectron paramagnetic resonanceIron toxicityNitric oxide toxicityPlasmid nicking assay2012-11-1510.1016/j.bmc.2012.09.03284867862123