Document Detail


Identification of carcinogen DNA adducts in human saliva by linear quadrupole ion trap/multistage tandem mass spectrometry.
MedLine Citation:
PMID:  20443584     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Erin E Bessette; Simon D Spivack; Angela K Goodenough; Tao Wang; Shailesh Pinto; Fred F Kadlubar; Robert J Turesky
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemical research in toxicology     Volume:  23     ISSN:  1520-5010     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-08-04     Completed Date:  2010-11-26     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1234-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Aminobiphenyl Compounds / analysis
Carcinogens / analysis*
DNA Adducts / analysis*
Deoxyguanosine / analogs & derivatives,  analysis
Female
Humans
Imidazoles / analysis
Male
Middle Aged
Saliva / chemistry*
Smoking
Tandem Mass Spectrometry / methods*
Grant Support
ID/Acronym/Agency:
K24 CA139054/CA/NCI NIH HHS; R01 CA106186/CA/NCI NIH HHS; R01 CA122320/CA/NCI NIH HHS; R01 CA122320/CA/NCI NIH HHS; R01 CA122320-03/CA/NCI NIH HHS; R21 ES014438/ES/NIEHS NIH HHS; R21 ES014438/ES/NIEHS NIH HHS; R21 ES014438-02/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Aminobiphenyl Compounds; 0/Carcinogens; 0/DNA Adducts; 0/Imidazoles; 142784-25-6/N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; 86408-34-6/N-(deoxyguanosin-8-yl)-4-aminobiphenyl; 909C6UN66T/2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; G9481N71RO/Deoxyguanosine
Comments/Corrections

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