The biological consequences of a carcinogen-DNA adduct are defined by the structure of the lesion and its position within the genome. Electrospray ionization ion trap mass spectrometry (ESI-ITMS) is shown here to be a sensitive and rapid approach capable of defining both of these parameters. Three isomeric oligonucleotides of the sequence 5′-CCGGAGGCC modified by the potent human carcinogen aflatoxin B1 (AFB1) at different guanines were analyzed by ESI-ITMS. All three samples possessed the same molecular ion confirming the presence of an intact aflatoxin moiety in each oligonucleotide. In addition, each sample displayed a characteristic fragmentation pattern that permitted unambiguous identification of the site of modification within the sequence. Furthermore, an AFB1-modified oligonucleotide was converted under alkaline conditions to its more stable formamidopyrimidine (FAPY) derivative. Analysis of this sample revealed the presence of a molecular ion corresponding to the presence of the FAPY adduct and a distinctive fragmentation pattern that paralleled the known chemical stability of the FAPY metabolite. This approach should be of general use in the determination of not only the nature and site of covalent modifications, but also the chemical stability of DNA adducts.
|Number of pages||7|
|Journal||Journal of the American Society for Mass Spectrometry|
|State||Published - 1998|