title: Tissue Distribution, Excretion and Pharmacokinetics of the Environmental Pollutant Dibenzo[def,p]chrysene in Mice.
abstract: Dibenzo[def,p]chrysene (DBP), a representative example of the class of polycyclic aromatic hydrocarbon (PAH), is known to induce tumors in multiple organ sites including the ovary, lung, mammary glands, and oral cavity in rodents. The goal of this study was to test the hypothesis that the levels of DBP and its metabolites that reach and retain the levels for an extended time in the target organs as well as the capacity of these organs to metabolize this carcinogen to active metabolites that can damage DNA may account for its tissue selective tumorigenicity. Therefore, we used the radiolabeled [(3)H] DBP to accurately assess the tissue distribution, excretion, and pharmacokinetics of this carcinogen. We also compared the levels of DBPDE-DNA adducts in a select target organ (ovary) and nontarget organs (kidney and liver) in mice treated orally with DBP. Our results showed that after 1 week, 91.40 ± 7.23% of the radioactivity was recovered in the feces; the corresponding value excreted in the urine was less than 2% after 1 week. After 24 h, the stomach had the highest radioactivity followed by the intestine and the liver; however, after 1 week, levels of the radioactivity in these organs were the lowest among tissues examined including the ovary and liver; the pharmacokinetic analysis of DBP was conducted using a one compartment open model. The level of (-)-anti-trans-DBPDE-dA in the ovaries (8.91 ± 0.08 adducts/10(7) dA) was significantly higher (p < 0.01) than the levels of adducts in kidneys (0.69 ± 0.09 adducts/10(7) dA) and livers (0.63 ± 0.11 adducts/10(7) dA). Collectively, the results of the tissue distribution and pharmacokinetic analysis may not fully support our hypothesis, but the capacity of the target organs vs nontarget organs to metabolize DBP to active intermediates that can damage DNA may account for its tissue selective tumorigenicity.
authors.affiliation: †Department of Biochemistry and Molecular Biology, ‡Department of Medicine, and §Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
authors.forename: Yuan-Wan
authors.initials: YW
authors.lastname: Sun
authors.affiliation: †Department of Biochemistry and Molecular Biology, ‡Department of Medicine, and §Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
authors.forename: Karam
authors.initials: K
authors.lastname: El-Bayoumy
authors.affiliation: †Department of Biochemistry and Molecular Biology, ‡Department of Medicine, and §Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
authors.forename: Cesar
authors.initials: C
authors.lastname: Aliaga
authors.affiliation: †Department of Biochemistry and Molecular Biology, ‡Department of Medicine, and §Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
authors.forename: Alaa S
authors.initials: AS
authors.lastname: Awad
authors.affiliation: †Department of Biochemistry and Molecular Biology, ‡Department of Medicine, and §Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
authors.forename: Krishne
authors.initials: K
authors.lastname: Gowda
authors.affiliation: †Department of Biochemistry and Molecular Biology, ‡Department of Medicine, and §Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
authors.forename: Shantu
authors.initials: S
authors.lastname: Amin
authors.affiliation: †Department of Biochemistry and Molecular Biology, ‡Department of Medicine, and §Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
authors.forename: Kun-Ming
authors.initials: KM
authors.lastname: Chen
mesh_terms: D000818:Animals; D001580:Benzopyrenes / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis; D004249:DNA Damage / Q000187:drug effects; D004785:Environmental Pollutants / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D005243:Feces / Q000737:chemistry; D005260:Female; D006207:Half-Life; D051379:Mice; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D014316:Tritium / Q000737:chemistry
chemical_list: D001580:Benzopyrenes; D018736:DNA Adducts; D004785:Environmental Pollutants; D014316:Tritium; D004247:DNA; C041517:dibenzo(a,l)pyrene