Screening for DNA adducts by data-dependent constant neutral loss-triple stage mass spectrometry with a linear quadrupole ion trap mass spectrometer.
A two-dimensional linear quadrupole ion trap mass spectrometer (LIT/MS) was employed to simultaneously screen for DNA adducts of environmental, dietary, and endogenous genotoxicants, by data-dependent constant neutral loss scanning followed by triple-stage mass spectrometry (CNL-MS3). The loss of the deoxyribose (dR) from the protonated DNA adducts ([M + H - 116]+) in the MS/MS scan mode triggered the acquisition of MS3 product ion spectra of the aglycone adducts [BH2]+. Five DNA adducts of the tobacco carcinogen 4-aminobiphenyl (4-ABP) were detected in human hepatocytes treated with 4-ABP, and three DNA adducts of the cooked-meat carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) were identified in the livers of rats exposed to MeIQx, by the CNL-MS3 scan mode. Buccal cell DNA from tobacco smokers was screened for DNA adducts of various classes of carcinogens in tobacco smoke including 4-ABP, 2-amino-9H-pyrido[2,3-b]indole (AalphaC), and benzo[a]pyrene (BaP); the cooked-meat carcinogens MeIQx, AalphaC, and 2-amino-1-methyl-6-phenylmidazo[4,5-b]pyridine (PhIP); and the lipid peroxidation products acrolein (AC) and trans-4-hydroxynonenal (HNE). The CNL-MS3 scanning technique can be used to simultaneously screen for multiple DNA adducts derived from different classes of carcinogens, at levels of adduct modification approaching 1 adduct per 108 unmodified DNA bases, when 10 microg of DNA is employed for the assay.
Bessette
Erin E
EE
Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
Goodenough
Angela K
AK
Langouët
Sophie
S
Yasa
Isil
I
Kozekov
Ivan D
ID
Spivack
Simon D
SD
Turesky
Robert J
RJ
D000611:Aminobiphenyl Compounds / Q000008:administration & dosage; D000818:Animals; D002273:Carcinogens / Q000032:analysis* / Q000737:chemistry; D002478:Cells, Cultured; D018736:DNA Adducts / Q000032:analysis* / Q000737:chemistry; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D009061:Mouth Mucosa / Q000737:chemistry / Q000187:drug effects; D011810:Quinoxalines / Q000008:administration & dosage; D051381:Rats; D052616:Solid Phase Extraction; D021241:Spectrometry, Mass, Electrospray Ionization
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D018736:DNA Adducts; D011810:Quinoxalines; C006757:4-biphenylamine; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline