Characterization of 2'-Deoxyadenosine Adducts Derived from 4-Oxo-2-nonenal, a Novel Product of Lipid Peroxidation

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• 作者：Seon Hwa Lee ; Diane Rindgen ; Roy H. Bible ; Jr. ; Elisabeth Hajdu ; and Ian A. Blair
• 刊名：Chemical Research in Toxicology
• 出版年：2000
• 出版时间：July 2000
• 年：2000
• 卷：13
• 期：7
• 页码：565 - 574
• 全文大小：249K
• 年卷期：v.13,no.7(July 2000)
• ISSN：1520-5010

文摘

Analysis of the reaction between 2'-deoxyadenosine and 4-oxo-2-nonenal by liquid chromatography/mass spectrometry revealed the presence of three major products (adducts A₁, A₂,and B). Adducts A₁ and A₂ were isomeric; they interconverted at room temperature, and theyeach readily dehydrated to form adduct B. The mass spectral characteristics of adduct Bobtained by collision-induced dissociation coupled with multiple tandem mass spectrometrywere consistent with those expected for a substituted etheno adduct. The structure of adductB was shown by NMR spectroscopy to be consistent with the substituted etheno-2'-deoxyadenosine adduct 1' '-[3-(2'-deoxy--D-erythropentafuranosyl)-3H-imidazo[2,1-i]purin-7-yl]heptane-2' '-one. Unequivocal proof of structure came from the reaction of adducts A₁ andA₂ (precursors of adduct B) with sodium borohydride. Adducts A₁ and A₂ each formed the samereduction product, which contained eight additional hydrogen atoms. The mass spectralcharacteristics of this reduction product established that the exocyclic amino group (N⁶) of2'-deoxyadenosine was attached to C-1 of the 4-oxo-2-nonenal. The reaction of 4-oxo-2-nonenalwith calf thymus DNA was also shown to result in the formation of substituted ethano adductsA₁ and A₂ and substituted etheno adduct B. Adduct B was formed in amounts almost 2 ordersof magnitude greater than those of adducts A₁ and A₂. This was in keeping with the observedstability of the adducts. The study presented here has provided additional evidence whichshows that 4-oxo-2-nonenal reacts efficiently with DNA to form substituted etheno adducts.