title: Dibenzo[a,l]pyrene induced DNA adduct formation in lung tissue in vivo.
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 20 mg 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.
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, 1007 Agricultural and Life Sciences Building, Corvallis, OR 97331-7302, USA.
authors.forename: Brinda
authors.initials: B
authors.lastname: Mahadevan
authors.forename: Andreas
authors.initials: A
authors.lastname: Luch
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Bravo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Atkin
authors.forename: Linda B
authors.initials: LB
authors.lastname: Steppan
authors.forename: Cliff
authors.initials: C
authors.lastname: Pereira
authors.forename: Nancy I
authors.initials: NI
authors.lastname: Kerkvliet
authors.forename: William M
authors.initials: WM
authors.lastname: Baird
mesh_terms: D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018736:DNA Adducts / Q000032:analysis*; D004249:DNA Damage; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
chemical_list: D001580:Benzopyrenes; D018736:DNA Adducts; C041517:dibenzo(a,l)pyrene