Journal
CHEMICAL RESEARCH IN TOXICOLOGY
Volume 23, Issue 7, Pages 1234-1244Publisher
AMER CHEMICAL SOC
DOI: 10.1021/tx100098f
Keywords
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Funding
- National Cancer Institute [R01 CA 122320]
- National Institute of Environmental Health Sciences [R21 ES014438]
- World Cancer Research Fund International [2007/58]
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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/MSn) 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-phenyl imidazo[4,5-b]pyridine (PhIP), 2-amino-9/1-pyrido[2,3-b]indole (A alpha C), 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/MSn, 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-A alpha C and (dG-C8-MeIQx were identified solely in saliva samples of three current smokers, and (dG-C8-4-A BP 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.
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