Dibenzo[a,l]pyrene induced DNA adduct formation in lung tissue in vivo

Mahadevan, Brinda; Luch, Andreas; Bravo, Claudia F.; Atkin, Jennifer; Steppan, Linda B.; Pereira, Cliff; Kerkvliet, Nancy I.; Baird, William M.

doi:10.1016/j.canlet.2004.11.056

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Volume 227, Issue 1 , Pages 25-32, 8 September 2005

Dibenzo[a,l]pyrene induced DNA adduct formation in lung tissue in vivo

Brinda Mahadevan
- Department of Environmental and Molecular Toxicology, Oregon State University, 1007 Agricultural and Life Sciences Building, Corvallis, OR 97331-7302, USA
Andreas Luch
- MIT Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Claudia F. Bravo
- Department of Environmental and Molecular Toxicology, Oregon State University, 1007 Agricultural and Life Sciences Building, Corvallis, OR 97331-7302, USA
Jennifer Atkin
- Department of Environmental and Molecular Toxicology, Oregon State University, 1007 Agricultural and Life Sciences Building, Corvallis, OR 97331-7302, USA
Linda B. Steppan
- Department of Environmental and Molecular Toxicology, Oregon State University, 1007 Agricultural and Life Sciences Building, Corvallis, OR 97331-7302, USA
Cliff Pereira
- Department of Statistics, Oregon State University, Corvallis, OR 97331, USA
Nancy I. Kerkvliet
- Department of Environmental and Molecular Toxicology, Oregon State University, 1007 Agricultural and Life Sciences Building, Corvallis, OR 97331-7302, USA
William M. Baird
- Department of Environmental and Molecular Toxicology, Oregon State University, 1007 Agricultural and Life Sciences Building, Corvallis, OR 97331-7302, USA
- Corresponding author. Tel.: +1 541 737 1886; fax: +1 541 737 0497.

Received 1 November 2004; received in revised form 23 November 2004; accepted 24 November 2004.

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are environmental carcinogens present in the atmosphere from combustion sources such as cigarette smoke, diesel exhaust, residential heating processes, and industrial coke production. To date, dibenzo[a,l]pyrene (DBP) has been found to be the strongest tumor-initiating PAH ever tested in rodent skin and mammary tumor models. Here we show for the first time that systemic exposure to DBP causes DNA damage in mouse lung tissue. C57BL/6 mice were gavaged with 1, 5 or 20mg DBP/kg body weight, daily for 10 days. Toxicity of DBP was revealed by a decrease in body and organ weight of mice while no apparent cell death was observed on P815 mastocytoma cells (allograft model) in vitro. However, treatment of P815 cells in vitro with the ultimate carcinogenic metabolite of DBP, the fjord region (−)-anti-11,12-diol 13,14-epoxide [(−)-anti-DBPDE], resulted in the total loss of cell viability. Lungs from the animals were removed and subjected to DBP-DNA adduct analysis. A dose dependent adduct formation was revealed by ³³P-postlabeling analysis of DNA from lung tissue. The majority of DNA adducts formed in lungs of mice after systemic exposure to DBP were contributed by (−)-anti-DBPDE. The data from this in vivo model are consistent with previous metabolic activation results obtained with DBP in human cells in culture.