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

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 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.

journal_name

Bioorg Med Chem

authors

Lewandowska H,Stępkowski TM,Sadło J,Wójciuk GP,Wójciuk KE,Rodger A,Kruszewski M

doi

10.1016/j.bmc.2012.09.032

subject

Has Abstract

pub_date

2012-11-15 00:00:00

pages

6732-8

issue

22

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(12)00744-4

journal_volume

20

pub_type

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