Phenylglycidyl ether adducts of 2′-deoxycytidine and 2′-deoxyadenosine: Stability in solution and structure analysis by electrospray tandem mass spectrometry

Abstract

The adducts of phenylglycidyl ether with 2'-deoxyadenosine (dAdo) and 2'-deoxycytidine (dCyd) exhibit structural modifications. The N-1 adduct of dAdo underwent rearrangement to the N-6 adduct; the N-3 adduct of dCyd was deaminated to the corresponding 2'-deoxyuridine adduct. These structural modifications were studied by using liquid chromatography-electrospray tandem mass spectrometry, and kinetic data for both reactions are presented. The low energy (+) collision-activated dissociation spectra of the dAdo adducts allow the two positional isomers N-1 versus N-6 to be distinguished. The structure of the latter is independently proven by an extended NMR study. For the dCyd and 2'-deoxyuridine adducts, information about the alkylation site is found in the (-) collision-activated dissociation spectra. These spectra show the presence of an unexpected N-4-alkylated dCyd in addition to the two epimeric N-3 adducts.

A nontargeted screening method for covalent DNA adducts and DNA modification selectivity using liquid chromatography-tandem mass spectrometry

“…PGE, an important industrial epoxide mainly used in the paint and the resin industry, can lead to modification of DNA [20]. When the neutral loss scan was used to screen the hydrolyzed DNA oligonucleotide (20 mer) that was reacted with PGE, multiple new peaks with a retention time in the range of 23.5-31.0 min were observed in the chromatogram ( Fig.…”

Detection of DNA damage in fish Oreochromis mossambicus induced by co-exposure to phenanthrene and nitrite by ESI-MS/MS

“…The N 1 adduct is known to yield a more stable aromatic product ion giving the most intense signal in the spectrum . The protonated adenine ion is generated by the loss of carcinogen and deoxysugar from the DNA adduct via a Mc Lafferty rearrangement (Lemiere et al 1996). Two complementary fragments at m/z 277 and 235 resulted from the cleavage of carcinogenbase bond at the exoamino group of purine.…”

Differentiation between isomeric phenylglycidyl ether adducts of 2′-deoxyguanosine and 2′-deoxyguanosine-5′-monophosphate using liquid chromatography/electrospray tandem mass spectrometry

“…The low-energy collision-activated dissociation (CAD) product ion spectra allow both differentiation between base and phosphate alkylation 10,11 and localization of the exact position of the alkyl group on the pyrimidine or purine moiety. 12 The advantages of MS/MS used for the differentiation between the different isomeric forms of DNA adducts are discussed in the literature. Differentiation was made between N 2 and C8 adducts of N-acetyl-2-aminofluorene of 2 0 -deoxyguanosine (dGuo), several methylated purines and dibenzo[a,l]pyrene adducts of adenine.…”

“…The PGE-dGuo reaction mixtures were obtained using the procedure described previously for dCyd and dAdo. 12 In order to obtain the deuterated analogues of the compounds present in the PGE-dGuo reaction mixture, the reaction of dGuo and PGE was repeated under conditions identical with those described earlier, 12 using solvents allowing the replacement of hydrogens with deuterium (MeOD and D 2 O). For the capillary LC analysis of this reaction mixture, D 2 O and MeOD were used in the mobile phase.…”