Coordination of iron ions in the form of histidinyl dinitrosyl complexes does not prevent their genotoxicity.
| Title: | Coordination of iron ions in the form of histidinyl dinitrosyl complexes does not prevent their genotoxicity. |
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| Authors: | Lewandowska H; Institute of Nuclear Chemistry and Technology, Dorodna 16, Warsaw, Poland.; Stępkowski TM; Sadło J; Wójciuk GP; Wójciuk KE; Rodger A; Kruszewski M |
| Source: | Bioorganic & medicinal chemistry [Bioorg Med Chem] 2012 Nov 15; Vol. 20 (22), pp. 6732-8. Date of Electronic Publication: 2012 Sep 25. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Country of Publication: England NLM ID: 9413298 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3391 (Electronic) Linking ISSN: 09680896 NLM ISO Abbreviation: Bioorg Med Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Elsevier Science; Original Publication: Oxford : New York : Pergamon Press, c1993- |
| MeSH Terms: | Ferrous Compounds/*chemistry ; Histidine/*chemistry ; Iron/*chemistry ; Nitrogen Oxides/*chemistry; DNA/chemistry ; DNA/metabolism ; Deferoxamine/pharmacology ; Ferrous Compounds/toxicity ; Ions/chemistry ; Iron/toxicity ; Nitrogen Oxides/toxicity ; Circular Dichroism ; DNA Breaks, Single-Stranded ; Electron Spin Resonance Spectroscopy ; Toxicity Tests |
| 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.; (Copyright © 2012 Elsevier Ltd. All rights reserved.) |
| Substance Nomenclature: | 0 (Ferrous Compounds); 0 (Ions); 0 (Nitrogen Oxides); 4QD397987E (Histidine); 68586-27-6 (dinitrosyl iron complex); 9007-49-2 (DNA); E1UOL152H7 (Iron); J06Y7MXW4D (Deferoxamine) |
| Entry Date(s): | Date Created: 20121016 Date Completed: 20130319 Latest Revision: 20131121 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.bmc.2012.09.032 |
| PMID: | 23063520 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't