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Biomarkers And Metabolic Mechanisms Of Tobacco Smoke-Induced Lung Disease, Matthew Alan Hartog
Biomarkers And Metabolic Mechanisms Of Tobacco Smoke-Induced Lung Disease, Matthew Alan Hartog
Legacy Theses & Dissertations (2009 - 2024)
The overall goal of the research conducted in this dissertation is to determine the role of cytochrome (CYP) P450-mediated xenobiotic bioactivation in the development of tobacco smoke-induced lung toxicity. The central hypothesis of this work is that CYP-mediated bioactivation of specific tobacco smoke constituents is an important contributor to the generation of tobacco smoke-induced lung inflammation and injury. The specific aims are 1) to demonstrate that CYP-mediated metabolism contributes to the onset of lung inflammation following tobacco smoke inhalation; 2) to demonstrate that specific tobacco smoke constituents undergo CYP-mediated bioactivation in vivo; 3) to demonstrate that CYP-mediated bioactivation of tobacco …
Organ-Specific Contribution Of P450 Enzymes To Bioactivation And Acute Respiratory Tract Toxicity Of Naphthalene, Nataliia Kovalchuk
Organ-Specific Contribution Of P450 Enzymes To Bioactivation And Acute Respiratory Tract Toxicity Of Naphthalene, Nataliia Kovalchuk
Legacy Theses & Dissertations (2009 - 2024)
Naphthalene (NA) is an omnipresent air pollutant and respiratory toxicant and a possible human lung carcinogen. NA induces cytotoxicity in airways following bioactivation by CYP (P450) enzymes. The overall goal of this study was to examine the relative contributions of hepatic and pulmonary CYPs to bioactivation, disposition and NA-induced pneumotoxicity in vivo. Substantial differences in the expression and enzymatic activity of P450s occur in various organs in human populations, which could modify susceptibility to NA-induced airway damage. The central hypothesis for this study was that NA has the potential to cause lung toxicity in humans and that the metabolism of …