Carcinogenesis Advance Access originally published online on November 17, 2006
Carcinogenesis 2007 28(5):1117-1121; doi:10.1093/carcin/bgl219
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Formation and persistence of DNA adducts formed by the carcinogenic air pollutant 3-nitrobenzanthrone in target and non-target organs after intratracheal instillation in rats
Division of Molecular Toxicology, German Cancer Research Center, INF 280, 69120 Heidelberg, Germany
1 Department of Biochemistry, Faculty of Science, Charles University, 128 40 Prague 2, Czech Republic
2 Section of Molecular Carcinogenesis, Institute of Cancer Research, Brookes Lawley Building, Sutton, Surrey SM2 5NG, UK
* To whom correspondence should be addressed. Tel: +49 6221 423348; Fax: +49 6221 423375; Email: h.schmeiser{at}dkfz.de
Sprague–Dawley rats were treated by intratracheal instillation with a single dose of 0.2 mg/kg body wt of 3-nitrobenzanthrone (3-NBA), and whole blood, lungs, pancreases, kidneys, urinary bladders, hearts, small intestines and livers were removed at various times after administration. At five posttreatment times (2 days, 2, 10, 20 and 36 weeks), DNA adducts were analysed in each tissue by 32P-postlabelling to study their long-term persistence. 3-NBA-derived DNA adducts consisting of the same adduct pattern were observed in all tissues from animals killed between 2 days and 36 weeks and between 2 days and 20 weeks in blood. DNA isolated from whole blood contained the same 3-NBA-specific adduct pattern as that found in tissues. Although total adduct levels in the blood were much lower than those found in the lung, the target organ of 3-NBA tumourigenicity, they were related (20–25%, R2 = 0.98) to the levels found in lung. In all organs, total adduct levels decreased over time to 20–30% of the initial levels till the latest time point (36 weeks) and showed a biphasic profile, with a rapid loss during the first 2 weeks followed by a much slower decline that reached a stable plateau at 20 weeks after treatment. These results show that uptake of 3-NBA by the lung induces high levels of specific DNA adducts in target and non-target organs of the rat. The correlation between DNA adducts in lung and blood suggests that persistent 3-NBA–DNA adducts in the blood may be useful biomarkers for human respiratory exposure to 3-NBA.
Abbreviations: 3-NBA, 3-nitrobenzanthrone; dG-N2-ABA, 2-(2'-deoxyguanosin-N2-yl)-3-aminobenzanthrone; nitro-PAH, nitropolycyclic aromatic hydrocarbon; TLC, thin-layer chromatography; HPLC, high performance liquid chromatography
Received September 8, 2006; revised November 1, 2006; accepted November 4, 2006.
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