Mutagenesis Advance Access originally published online on January 31, 2007
Mutagenesis 2007 22(2):135-145; doi:10.1093/mutage/gel067
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DNA adduct formation and oxidative stress from the carcinogenic urban air pollutant 3-nitrobenzanthrone and its isomer 2-nitrobenzanthrone, in vitro and in vivo
Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 57 Huddinge, Stockholm, Sweden 1Department of Public Health, Sagami Women's University, Sagamihara, Kanagawa 228-8533, Japan 2National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
The carcinogenic vehicle emission product 3-nitrobenzanthrone (3-NBA) is known to rearrange in the atmosphere to the isomer 2-nitrobenzanthrone (2-NBA), which exists in 70-fold higher concentration in ambient air. The genotoxicity of 2-NBA and 3-NBA was studied both in vitro (human cell lines A549 and HepG2) and in vivo (F344 female rats intra-tracheally administered 5 mg/kg body weight of 3-NBA) models, using the 32P-HPLC and the single-cell gel electrophoresis (Comet assay) methods. In vitro, also the parent compound benzanthrone (BA) and the metabolite 3-aminobenzanthrone (3-ABA) were evaluated. 3-NBA gave highest levels of DNA adducts in the two cell lines, but significantly higher in HepG2 (relative adduct level 
500 adducts/108 normal nucleotides), whereas 2-NBA formed about one-third and one-twentieth of the DNA adduct amount in A549 and HepG2 cells, respectively. 3-ABA formed only minute amounts of DNA adducts and only in the A549 cells, whereas BA did not give rise to any detectable levels. The DNA adduct patterns from 3-NBA were similar between the two model systems, but differed somewhat for 2-NBA. The oxidative stress induced by BA was almost as high as what was observed for 3-NBA and 3-ABA in both cell lines, and 2-NBA induced lowest level of oxidative stress. The oxidative stress and DNA adduct level, in whole blood, was significantly increased by 3-NBA but not by 2-NBA. However, 2-NBA showed similar toxicity to 3-NBA, with respect to DNA adduct formation in vivo, hence it is important to further study 2-NBA as a potential contributor to health risk. While DNA adduct level in the 3-NBA-exposed animals reached a peak around 1 and 2 days after instillation, 2-NBA-treated animals showed a tendency towards a continuing increase at the end of the study.
* To whom correspondence should be addressed. Tel: +46 8 608 92 20; Fax: +46 8 774 68 33; Email: lennart.moller{at}biosci.ki.se
Received on September 7, 2006; revised on October 25, 2006; accepted on November 21, 2006.
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