Published in Cancer Detection and Prevention 1995; 19(1).

Analysis of heterocyclic aromatic amine adducts of DNA using capillary liquid chromatography/electrospray ionization/tandem mass spectrometry

D Rindgen1, RJ Turesky2, P Vouros1

1Dept. of Chemistry and the Barnett Institute, Northeastern University, Boston, MA 02115, USA, 2Nestle Ltd. Research Center, Lausanne, Switzerland.

We have investigated the use of capillary HPLC/tandem mass spectrometry with electrospray ionization (ESI) for detection of 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine (PhIP) adducts of deoxyguanosine (dG). PhIP is the most abundant heterocyclic aromatic amine in cooked food and has been shown to induce lymphomas in mice and colon and mammary carcinomas in rats. Sensitive and specific detection was achieved by monitoring a transition unique to this compound with detection limits of 40 pg obtained for the dG-C8-PhIP standard. Collision induced dissociation of dG-C8-PhIP produced fragment ion spectra characteristic of the adduct. The method was applied to the analysis of an in vitro DNA reaction mixture and the data confirmed the presence of the dG-C8-PhIP adduct as well as two additional PhIP-related compounds. An ion not detected with the dG-C8-PhIP standard appeared in the constant neutral loss scan and comparison of its fragmentation behavior with the standard allowed for structural assignment.

Paper presented at the International Symposium on the Impact of Biotechnology on Predictive Oncology and Therapy; Boston, Massachusetts; December 11 - 13, 1994; in the section on Diagnostic Markers.