Coordination of iron ions in the form of histidinyl dinitrosyl complexes does not prevent their genotoxicity

Hanna Lewandowska, Tomasz M. Stepkowski, Jarosław Sadło, Grzegorz P. Wójciuk, Karolina E. Wójciuk, Alison Rodger, Marcin Kruszewski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Formation 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.

Original languageEnglish
Pages (from-to)6732-6738
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number22
DOIs
Publication statusPublished - 15 Nov 2012
Externally publishedYes

Keywords

  • Circular dichroism
  • DNA
  • Electron paramagnetic resonance
  • Iron toxicity
  • Nitric oxide toxicity
  • Plasmid nicking assay

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