Date of Award

1-1-2017

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Environmental Health Sciences

Content Description

1 online resource (ii, xiii, 118 pages) : illustrations (some color)

Dissertation/Thesis Chair

Xinxin Ding

Committee Members

David Spink, Qing-Yu Zhang, Laurence Kaminsky, Thomas Begley

Keywords

bioactivation, naphthalene, P450, respiratory tract, Cytochrome P-450, Naphthalene, Pulmonary toxicology, Cytochrome P-450 Enzyme System

Subject Categories

Environmental Health | Toxicology

Abstract

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 NA in both lung and liver influence the consequence of NA exposure on an individual basis. Three projects were undertaken to address this hypothesis.

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