Coordination of iron ions in the form of histidinyl dinitrosyl complexes does not prevent their genotoxicity |
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Authors: | Hanna Lewandowska Tomasz M. Stępkowski Jarosław Sadło Grzegorz P. Wójciuk Karolina E. Wójciuk Alison Rodger Marcin Kruszewski |
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Affiliation: | 1. Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland;2. Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, United Kingdom;3. Independent Laboratory of Molecular Biology, Institute of Rural Health, ul. Jaczewskiego 2, 20-950 Lublin, Poland |
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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. |
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