Identification of carcinogen DNA adducts in human saliva by linear quadrupole ion trap/multistage tandem mass spectrometry

Erin E. Bessette, Simon D. Spivack, Angela K. Goodenough, Tao Wang, Shailesh Pinto, Fred F. Kadlubar, Robert J. Turesky

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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 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-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 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.

Original languageEnglish (US)
Pages (from-to)1234-1244
Number of pages11
JournalChemical Research in Toxicology
Volume23
Issue number7
DOIs
StatePublished - Jul 19 2010

Fingerprint

DNA Adducts
Mass spectrometers
Tandem Mass Spectrometry
Saliva
Carcinogens
Mass spectrometry
Ions
Tobacco
Amines
Quinoxalines
DNA
Electrospray ionization
Meats
Smoke
Liquid Chromatography
Liquid chromatography
Meat
Nutrition
Volunteers
Assays

ASJC Scopus subject areas

  • Toxicology

Cite this

Identification of carcinogen DNA adducts in human saliva by linear quadrupole ion trap/multistage tandem mass spectrometry. / Bessette, Erin E.; Spivack, Simon D.; Goodenough, Angela K.; Wang, Tao; Pinto, Shailesh; Kadlubar, Fred F.; Turesky, Robert J.

In: Chemical Research in Toxicology, Vol. 23, No. 7, 19.07.2010, p. 1234-1244.

Research output: Contribution to journalArticle

Bessette, Erin E. ; Spivack, Simon D. ; Goodenough, Angela K. ; Wang, Tao ; Pinto, Shailesh ; Kadlubar, Fred F. ; Turesky, Robert J. / Identification of carcinogen DNA adducts in human saliva by linear quadrupole ion trap/multistage tandem mass spectrometry. In: Chemical Research in Toxicology. 2010 ; Vol. 23, No. 7. pp. 1234-1244.
@article{cdf87cdd99ca477686479187f54105e4,
title = "Identification of carcinogen DNA adducts in human saliva by linear quadrupole ion trap/multistage tandem mass spectrometry",
abstract = "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 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-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 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.",
author = "Bessette, {Erin E.} and Spivack, {Simon D.} and Goodenough, {Angela K.} and Tao Wang and Shailesh Pinto and Kadlubar, {Fred F.} and Turesky, {Robert J.}",
year = "2010",
month = "7",
day = "19",
doi = "10.1021/tx100098f",
language = "English (US)",
volume = "23",
pages = "1234--1244",
journal = "Chemical Research in Toxicology",
issn = "0893-228X",
publisher = "American Chemical Society",
number = "7",

}

TY - JOUR

T1 - Identification of carcinogen DNA adducts in human saliva by linear quadrupole ion trap/multistage tandem mass spectrometry

AU - Bessette, Erin E.

AU - Spivack, Simon D.

AU - Goodenough, Angela K.

AU - Wang, Tao

AU - Pinto, Shailesh

AU - Kadlubar, Fred F.

AU - Turesky, Robert J.

PY - 2010/7/19

Y1 - 2010/7/19

N2 - 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 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-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 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.

AB - 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 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-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 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.

UR - http://www.scopus.com/inward/record.url?scp=77955342547&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955342547&partnerID=8YFLogxK

U2 - 10.1021/tx100098f

DO - 10.1021/tx100098f

M3 - Article

VL - 23

SP - 1234

EP - 1244

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

SN - 0893-228X

IS - 7

ER -