Coordination of iron ions in the form of histidinyl dinitrosyl complexes does not prevent their genotoxicity.
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 10mM 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 Fe(2+) 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 1μM 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.
Institute of Nuclear Chemistry and Technology, Dorodna 16, Warsaw, Poland.
Hanna
H
Lewandowska
Tomasz M
TM
Stępkowski
Jarosław
J
Sadło
Grzegorz P
GP
Wójciuk
Karolina E
KE
Wójciuk
Alison
A
Rodger
Marcin
M
Kruszewski
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded; D003676:Deferoxamine / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005296:Ferrous Compounds / Q000737:chemistry* / Q000633:toxicity; D006639:Histidine / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D007501:Iron / Q000737:chemistry* / Q000633:toxicity; D009589:Nitrogen Oxides / Q000737:chemistry* / Q000633:toxicity; D018675:Toxicity Tests
D005296:Ferrous Compounds; D007477:Ions; D009589:Nitrogen Oxides; D006639:Histidine; C073661:dinitrosyl iron complex; D004247:DNA; D007501:Iron; D003676:Deferoxamine