| 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. |
