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Characterization of DNA adducts from lung tissue of asphalt fume-exposed mice by nanoflow liquid chromatography quadrupole time-of-flight mass spectrometry.
Wang-JJ; Marshall-WD; Frazer-DG; Law-B; Lewis-DM
Anal Biochem 2003 Nov; 322(1):79-88
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 (4 h/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.
Analytical-methods; Chromatographic-analysis; Mass-spectrometry; Asphalt-fumes; DNA-adducts; Laboratory-animals; Animal-studies; Animals; Polycyclic-aromatic-hydrocarbons; Exposure-assessment; Exposure-levels; Bioassays; Lung-tissue; Benzopyrenes
National Institute for Occupational Safety and Health, Health Effects Laboratory Division, 1095 Willowdale Road, Morgantown, WV 26505
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Page last reviewed: April 12, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division