Benzo(A)Pyrene and Benzo(A)Pyrene-induced protein adducts in hair as biomarkers of toxic Benzo(A)Pyrene exposures

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Title Benzo(A)Pyrene and Benzo(A)Pyrene-induced protein adducts in hair as biomarkers of toxic Benzo(A)Pyrene exposures
Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Campbell, Sarah Colleen
Date 2011-08
Description Cigarette smoking is the leading cause of preventable death in the United States. While there are more than 4,000 chemicals found in tobacco smoke, the polycyclic aromatic hydrocarbons (PAHs) have been clearly demonstrated to contribute to smoking-related cancers. Of this group of compounds, benzo(a)pyrene (B(a)P) is concidered to be the most carcinogenic and its ability to cause lung tumors is well documented. Many conventional biomarker assays conducted today use the measurement of nicotine (and its metabolite cotinine) in blood, urine, or oral fluids for assessment of tobacco smoke exposure. However, these conventional assays do not measure exposure to carcinogenic compounds and are sensitive only to recent smoke exposures. Due to the ease of hair sampling and its extended detection window of substances incorporated into its matrix, this dissertational research proposes a promising new tool for the assessment of toxic tobacco smoke exposure. We investigated the disposition of B(a)P and its electrophilic reactive metabolite, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-benzo(a)pyrene (BPDE), in rat and human hair. BPDE is one of the most potent mutagens and carcinogens known, and forms protein and DNA adducts in iv multiple tissues. Our overarching hypothesis was that B(a)P and BPDE-protein adducts in hair can be used as biomarkers of toxic B(a)P exposure. The data presented in this dissertation demonstrate that B(a)P and BPDE-protein adducts are incorporated into rat hair in a dose-dependent manner. While B(a)P incorporation into rat hair is not dependent upon pigment content, BPDE-protein adducts concentrations are significantly greater in pigmented vs. nonpigmented hair. Gross histopathological changes in rat lung tissue, such as alveolar wall thickening, decreased air space, and macrophage hyperplasia were visually evident in rats 14 days after B(a)P administration. Immunohistochemistry staining for myeloperoxide content (a marker for neutrophils) in the lung tissue of B(a)P-dosed rats was also significantly greater than vehicle control rats. B(a)P can be detected in human hair, but BPDE-protein adducts could not be detected, despite evidence of active smoking status via plasma cotinine concentrations. The results of this dissertational research demonstrate that hair may serve as an easily accessible surrogate tissue for the detection of a biomarker of toxic tobacco smoke exposure.
Type Text
Publisher University of Utah
Subject Biochemical markers; Tobacco - Toxicology
Subject MESH Genetic Markers; Dihydroxydihydrobenzopyrenes; Melanins; Benzopyrenes; Nicotine; Cotinine; Polycyclic Hydrocarbons, Aromatic; Carcinogens; Tobacco Smoke Pollution; Environmental Exposure; Hair; Hair Follicle; Hair Color; Genetic Predisposition to Disease; DNA Adducts; Xenobiotics; Cytochrome P-450 Enzyme System; Inflammation; Benzo(a)pyrene
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital reproduction of Benzo(A)Pyrene and Benzo(A)Pyrene-Induced Protein Adducts in Hair as Biomarkers of Toxic Benzo(A)Pyrene Exposures. Spencer S. Eccles Health Sciences Library. Print version available at J. Willard Marriott Library Special Collections.
Rights Management Copyright © Sarah Colleen Campbell 2011
Format application/pdf
Format Medium application/pdf
Format Extent 5,659,019 bytes
Source Original in Marriott Library Special Collections, RA4.5 2011.C26
ARK ark:/87278/s65m9dw9
Setname ir_etd
ID 196335
Reference URL https://collections.lib.utah.edu/ark:/87278/s65m9dw9
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