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Carcinogenesis Advance Access published online on November 17, 2006
Carcinogenesis, doi:10.1093/carcin/bgl219
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 8, 2006
Revised November 1, 2006
Accepted November 4, 2006

CARCINOGENESIS

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

Christian A. Bieler 1, Michael G. Cornelius 1, Marie Stiborova 2, Volker M. Arlt 3, Manfred Wiessler 1, David H. Phillips 3, and Heinz H. Schmeiser 1 *

1 German Cancer Research Center, Division of Molecular Toxicology, INF 280, 69120 Heidelberg, Germany
2 Department of Biochemistry, Faculty of Science, Charles University, 128 40 Prague 2, The Czech Republic
3 Institute of Cancer Research, Section of Molecular Carcinogenesis, Brookes Lawley Building, Sutton, Surrey SM2 5NG, United Kingdom

* To whom correspondence should be addressed.
Heinz H. Schmeiser, E-mail: h.schmeiser{at}dkfz.de


  Abstract

Sprague-Dawley rats were treated by intratracheal instillation with a single dose of 0.2 mg/kg body weight 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 post-treatment 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 sacrificed 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 two 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.

Keywords: 3-nitrobenzanthrone; DNA adducts; 32P-postlabelling; diesel exhaust; intratracheal instillation; adduct persistence.
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