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 the heterocyclic aromatic amines 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-9H-pyrido[2,3-b]indole (AalphaC), 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 MS(3) 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-AalphaC 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 10(8) 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.
Bessette
Erin E
EE
Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
Spivack
Simon D
SD
Goodenough
Angela K
AK
Wang
Tao
T
Pinto
Shailesh
S
Kadlubar
Fred F
FF
Turesky
Robert J
RJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000611:Aminobiphenyl Compounds / Q000032:analysis; D002273:Carcinogens / Q000032:analysis*; D018736:DNA Adducts / Q000032:analysis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000737:chemistry*; D012907:Smoking; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D018736:DNA Adducts; D007093:Imidazoles; C078255:N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C053420:N-(deoxyguanosin-8-yl)-4-aminobiphenyl; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D003849:Deoxyguanosine