Identification of Carcinogen DNA Adducts in Human Saliva by Linear Quadrupole Ion Trap/Multistage Tandem Mass Spectrometry

DNA adducts of carcinogens derived from tobacco smoke and cooked meat were identified by liquid chromatography−electrospray ionization/multistage tandem mass spectrometry (LC-ESI/MS/MS n ) in saliva samples from 37 human volunteers on unrestricted diets. The N-(deoxyguanosin-8-yl) (dG-C8) adducts of...

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Bibliographic Details
Published in:Chemical research in toxicology 2010-07, Vol.23 (7), p.1234-1244
Main Authors: Bessette, Erin E, Spivack, Simon D, Goodenough, Angela K, Wang, Tao, Pinto, Shailesh, Kadlubar, Fred F, Turesky, Robert J
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Aminobiphenyl Compounds - analysis
Carcinogens - analysis
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - analysis
DNA Adducts - analysis
Female
Humans
Imidazoles - analysis
Male
Middle Aged
Saliva - chemistry
Smoking
Tandem Mass Spectrometry - methods
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Summary:DNA adducts of carcinogens derived from tobacco smoke and cooked meat were identified by liquid chromatography−electrospray ionization/multistage tandem mass spectrometry (LC-ESI/MS/MS n ) in saliva samples from 37 human volunteers on unrestricted diets. The N-(deoxyguanosin-8-yl) (dG-C8) adducts of the heterocyclic aromatic amines 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-9H-pyrido[2,3-b]indole (AαC), 2-amino-3,8-dimethylmidazo[4,5-f]quinoxaline (MeIQx), and the aromatic amine, 4-aminobiphenyl (4-ABP), were characterized and quantified by LC-ESI/MS/MS n , employing consecutive reaction monitoring at the MS3 scan stage mode with a linear quadrupole ion trap (LIT) mass spectrometer (MS). DNA adducts of PhIP were found most frequently: dG-C8-PhIP was detected in saliva samples from 13 of 29 ever-smokers and in saliva samples from 2 of 8 never-smokers. dG-C8-AαC and dG-C8-MeIQx were identified solely in saliva samples of three current smokers, and dG-C8-4-ABP was detected in saliva from two current smokers. The levels of these different adducts ranged from 1 to 9 adducts per 108 DNA bases. These findings demonstrate that PhIP is a significant DNA-damaging agent in humans. Saliva appears to be a promising biological fluid in which to assay DNA adducts of tobacco and dietary carcinogens by selective LIT MS techniques.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx100098f