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' C--O bond adjacent to the modified base in MS/MS analyses readily enabled the identification of the AA-binding site in ODNs.
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