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Characterization of the DNA adducts induced by aristolochic acids in oligonucleotides by electrospray ionization tandem mass spectrometry
Author(s) -
Chan Wan,
Yue Hao,
Wong Ricky N. S.,
Cai Zongwei
Publication year - 2008
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.3791
Subject(s) - chemistry , electrospray ionization , adduct , tandem mass spectrometry , oligonucleotide , guanine , mass spectrometry , dna , stereochemistry , biochemistry , chromatography , organic chemistry , nucleotide , gene
Metabolic activation of carcinogenic aristolochic acids (AA) produces reactive aristolactam‐nitrenium ion intermediates. Electrophilic attack of the aristolactam‐nitrenium ion via its C7 position to the exocyclic amino group in the purine bases leads to the formation of DNA adducts. DNA‐binding assays have demonstrated that carcinogens show site‐ and sequence‐specificity and the biological consequence is defined by the nature of binding as well as their position in the genome. In this study, electrospray ionization tandem mass spectrometry was applied for the identification and position mapping of DNA adducts in oligonucleotides (ODNs). The developed method was successfully applied for the analysis of unmodified and AA‐modified ODNs (5′‐TTTATT‐3′, 5′‐TTTGTT‐3′ and 5′‐TACATGTGT‐3′). The observation of the modified bases (modified adenine and guanine) together with the complementary product ions ([a n ‐B* n ] − , w − ) from the cleavage of the 3′ CO bond adjacent to the modified base in MS/MS analyses readily enabled the identification of the AA‐binding site in ODNs. Copyright © 2008 John Wiley & Sons, Ltd.