All ETDs from UAB

Advisory Committee Chair

Michelle V Fanucchi

Advisory Committee Members

Scott W Ballinger

James A Mobley

Joanne E Murphy-Ullrich

Edward M Postlethwait

Victor J Thannickal

Document Type

Dissertation

Date of Award

2012

Degree Name by School

Doctor of Philosophy (PhD) School of Public Health

Abstract

In the U.S., approximately 37 million children reside in geographic locales that experience unhealthy ozone levels. This population is of great concern as they are undergoing active lung growth and cellular differentiation which may alter their susceptibility to inhaled toxicants. Epidemiological and animal studies indicate that early life ozone exposure results in altered lung development, potentially facilitating predisposition to chronic pulmonary conditions in adulthood. The goal of this dissertation was to evaluate short and long-term effects of ozone exposure in the developing lung. The first study evaluated acute effects of ozone exposure in the postnatal and adult lung. The results indicate that site-specific ozone-induced airway lesions, as evidenced by plasma membrane permeability, differed by age with rats being most susceptible at 14 days postnatal (DPN). Additionally, cell membrane permeability was positively correlated with increased mitochondrial DNA damage. The second study evaluated proliferation and recovery in the proximal conducting airway (site of injury following 4 hour exposure) and parenchyma (region undergoing substantial postnatal growth) following a single acute exposure. Rats exposed to ozone at 7 DPN had increased proliferation in the proximal airways after 7 days of recovery but no significant changes in the alveolar region at any recovery time point. In contrast, rats exposed at 14 DPN had increased proliferation 24 hours after exposure in both the airway and alveolar regions. The last study evaluated the effects of long-term exposure initiated during the early postnatal period on the lung and epithelial lining fluid (ELF). In the ELF, small molecular weight antioxidants and protein composition were not significantly altered by ozone exposure. Airway wall smooth muscle thickness decreased while intracellular mucus staining increased in the proximal conducting airways of ozone exposed mice. Ozone-induced alterations in antioxidant response gene expression differed between male and female mice; however, few proteomic alterations were observed in the lung. In summary, these studies suggest that during the postnatal period, responses to inhaled toxicants may be altered at different developmental stages by underlying processes, such as proliferation and differentiation. These age-specific responses may partially explain differential outcomes between early life and adult exposures.

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