Carcinogenesis Advance Access originally published online on May 25, 2005
Carcinogenesis 2005 26(10):1821-1828; doi:10.1093/carcin/bgi141
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Carcinogenesis vol.26 no.10 © Oxford University Press 2005; all rights reserved.
DNA adduct and tumor formations in rats after intratracheal administration of the urban air pollutant 3-nitrobenzanthrone
Department for Biosciences at Novum, Karolinska Institutet, SE-141 57 Huddinge, Stockholm, Sweden, 1 Department of Pathology, Kagawa Nutrition University, Sakado, Saitama 350-0288, Japan, 2 Department of Community Environmental Science, National Institute of Public Health, Shirokanedai, Tokyo 108-8638, Japan and 3 Department of Public Health, Sagami Women's University, Sagamihara, Kanagawa 228-8533, Japan
* To whom correspondence should be addressed. Tel: +46 8 608 9233; Fax: +46 8 774 6833; Email: lennart.moller{at}biosci.ki.se
3-Nitrobenzanthrone (3-NBA) has been isolated from diesel exhaust and airborne particles and identified as a potent direct-acting mutagen in vitro and genotoxic agent in vivo. In order to evaluate the in vivo toxicity and carcinogenicity of 3-NBA in a situation corresponding to inhalation, a combined short-term and lifetime study with intratracheal (i.t.) instillation in female F344 rats was performed. DNA adduct formation, as a marker for the primary effect and analyzed by 32P-HPLC after single instillation, showed a few major DNA adducts and a rapid increase with a peak after 2 days, followed by a decline. No DNA adducts above the background level were observed after 16 days. The highest DNA adduct formation was observed in lung [
250 DNA adducts/108 normal nucleotides (NN)] closely followed by kidney (200 DNA adducts/108 NN), whereas liver contained only 12% (30 DNA adducts/108 NN) of the levels of DNA adducts found in lung. In the tumor study, squamous cell carcinomas were found after 7–9 months in the high-dose group (total dose of 2.5 mg 3-NBA) and after 10–12 months in the low-dose group (total dose of 1.5 mg 3-NBA). The fraction of squamous cell carcinoma out of the total amount of tumors observed at the end of experiment at 18 months, corresponded to 3/16 and 11/16 in the low- and high-dose group, respectively. A single case of adenocarcinoma was also observed in each group. In the control group, no tumors were observed during the entire study of 18 months. In addition, a few cases of squamous metaplasia were also observed in the lung in both dose groups but not in the controls. In conclusion, 3-NBA forms DNA adducts in the lung immediately after i.t. administration but almost all DNA adducts were eliminated after 16 days. Tumor formation in two dose groups was observed in a dose-dependent manner with squamous cell carcinomas as the predominant tumor type at high exposure.
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