Date of Award

1-1-2013

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

School of Public Health

Content Description

1 online resource (xvii, 187 pages) : illustrations (some color)

Dissertation/Thesis Chair

Xinxin Ding

Committee Members

Laurence Kaminsky, David Spink, Qing-Yu Zhang, Bruce Herron

Keywords

LUNG TUMORIGENESIS, NAPHTHALENE, NICOTINE, NNK, P450, TOBACCO DEPENDENCE, Cytochrome P-450, Nicotine addiction, Carcinogenesis, Naphthalene, Mice as laboratory animals

Subject Categories

Pharmacology | Public Health | Toxicology

Abstract

The overall aim of this study is to better define the roles of P450 enzymes, particularly those in the CYP2A, 2B, and 2F gene subfamilies, in the metabolism and actions of tobacco-related chemicals. Tobacco smoke contains numerous compounds that are deleterious to health, including the primary addictive component nicotine and procarcinogenic compounds, such as naphthalene (NA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Our main hypotheses are i) that CYP2A and 2B enzymes are largely responsible for nicotine metabolism, and they can impact nicotine dependence; and ii) that CYP2A, 2B, and 2F enzymes play important and tissue-specific roles in NA and NNK bioactivation, leading to lung toxicity and lung cancer. The specific aims are 1) to study the role of CYP2A and CYP2B in nicotine metabolism and dependence; 2) to study the role of CYP2F2 on NA-induced respiratory tract toxicity; 3) to study the role of CYP2 cluster in NNK bioactivation and lung tumorigenesis; and 4) to characterize human CYP2F1 expression and activity toward NA.

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