title: Characterization of DNA adducts from lung tissue of asphalt fume-exposed mice by nanoflow liquid chromatography quadrupole time-of-flight mass spectrometry.
abstract: A bioanalytical method based on nanoflow liquid chromatography coupled to a hybrid quadrupole orthogonal acceleration time-of-flight mass spectrometry was developed to characterize selected polyaromatic hydrocarbon (PAH)-DNA adducts. The collision-induced dissociation of analytes results in characteristic fragmentation patterns that can be utilized to identify the DNA adducts. In the experiment, 32 B6C3F1 mice were exposed daily (4h/day) to asphalt fume in a whole-body inhalation chamber for 10 days; 16 nonexposed mice served as controls. The asphalt fume was generated at 180 degrees C and the concentrations of PAHs in the animal exposure chamber ranged from 152 to 198 mg/m3. The DNA adducts N2-deoxyguanosine-benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (N2-dG-BPDE); N6-deoxyadenosine-benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (N6-dA-BPDE), and N4-deoxycytidine-benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (N4-dC-BPDE) were identified. The concentrations of N2-dG-BPDE, N6-dA-BPDE, and N4-dC-BPDE adducts were determined to be 1.17, 0.97, and 0.68 pmol/mg DNA, respectively, in the lung tissue of exposed mice using the nanoflow technique. The total DNA adducts in exposed lung tissue was determined to be 8.35 pmol/mg DNA by 32P-postlabeling assay. In total, the results indicated that PAH DNA adducts were significantly elevated (p < 0.001) in the lung tissue of asphalt-fume-exposed mice relative to tissue from control animals.
authors.affiliation: National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Morgantown, WV 26505, USA. juw9@cdc.gov
authors.forename: Jin J
authors.initials: JJ
authors.lastname: Wang
authors.forename: William D
authors.initials: WD
authors.lastname: Marshall
authors.forename: David G
authors.initials: DG
authors.lastname: Frazer
authors.forename: Brandon
authors.initials: B
authors.lastname: Law
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Lewis
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D000818:Animals; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000737:chemistry*; D006838:Hydrocarbons / Q000633:toxicity; D008168:Lung / Q000737:chemistry* / Q000187:drug effects; D013058:Mass Spectrometry; D051379:Mice; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry*
chemical_list: D002274:Carcinogens, Environmental; D018736:DNA Adducts; D006838:Hydrocarbons; D011084:Polycyclic Aromatic Hydrocarbons; C095911:polycyclic aromatic hydrocarbons-DNA adduct; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C006647:asphalt