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Banasiewicz, M; Nelson, G; Swank, A; Grubor, N; Ross, J; Nesnow, S; Köfeler, H; Small, GJ; Jankowiak, R.
Identification and quantitation of benzoapyrene-derived DNA adducts formed at low adduction level in mice lung tissue.
ANAL BIOCHEM. 2004; 334(2): 390-400. Doi: 10.1016/j.ab.2004.08.006
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Co-Autor*innen der Med Uni Graz
Köfeler Harald
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Abstract:
The two major metabolic pathways of benzo[a]pyrene (BP) that lead to DNA lesions are monooxygenation that results in diolepoxides (BPDE) and one-electron oxidation that yields a BP radical cation. These pathways result in formation of stable and depurinating DNA adducts, respectively. Most in vivo animal studies with BP, however, have employed dosage/DNA adduct levels several orders of magnitude higher than the DNA damage level expected from environmentally relevant exposures. Presented are results of experiments in which A/J strain mice were intraperitoneally exposed to 50-microg/g doses of BP. It is shown that non-line-narrowed fluorescence and fluorescence line-narrowing spectroscopies possess the selectivity and sensitivity to distinguish between helix-external, base-stacked, and intercalated conformations of DNA-BPDE adducts formed in lung tissue. Concentrations measured by 32P postlabeling 2 and 3 days after intraperitoneal injection were 420-430 and 600-830 amol BPDE-type adducts per microg DNA. The external and base-stacked conformations are attributed mainly to (+)-trans-anti-BPDE-N2dG and the intercalated conformations to (+)-cis-anti adducts. A stable adduct derived from 9-OH-BP-4,5-epoxide was also detected at a concentration about a factor of 10 lower than the above concentrations. The DNA supernatants were analyzed for the presence of depurinating BP-derived adducts by capillary electrophoresis laser-induced fluorescence and high-performance liquid chromatography mass spectrometry.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Benzo(a)pyrene - chemistry
DNA Adducts - analysis
Lung - drug effects
Mice - drug effects
Molecular Structure - drug effects
Spectrometry, Fluorescence - drug effects
Temperature - drug effects

Find related publications in this database (Keywords)
benzo[a]pyrene
benzo[a]pyrene diolepoxide
fluorescence line-narrowing spectroscopy
DNA adducts
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