Date on Master's Thesis/Doctoral Dissertation

8-2016

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Physiology and Biophysics

Degree Program

Physiology and Biophysics, PhD

Committee Chair

Bhatnagar, Aruni

Committee Co-Chair (if applicable)

O'Toole, Timothy

Committee Member

O'Toole, Timothy

Committee Member

Schuschke, Dale

Committee Member

Lominadze, David

Committee Member

D'Souza, Stanley

Author's Keywords

benzene; air pollution; insulin resistance; oxidative stress; stem cells; inflammation

Abstract

The rapid and recent increase in the global epidemic of diabetes and cardiovascular disease suggests a strong component of the environment is contributing. Benzene is a ubiquitous volatile pollutant generated by cigarette smoke, automobile exhaust, wildfires and industrial activities. Consequently, it is found in almost all urban and rural air samples. Benzene is known to cause hematotoxicity and its metabolism generates oxidative stress. Although, benzene has been studied for many years, few investigations have probed what influence benzene exposure may have on other physiological processes. Here we hypothesize that benzene metabolism by hepatic-CYP450 2E1 generates oxidative stress and inflammation, which then promote insulin resistance and endothelial dysfunction. To test this hypothesis, we measured hematological progenitor differentiation and circulating blood cell types as well as indices of oxidative stress, vascular damage, insulin resistance and stem cell function to assess relative sensitivity of hematological and vascular biomarkers. Our findings show that benzene-exposed mice exhibit oxidative stress, inflammation, vascular damage, insulin resistance, thrombosis with diminished vascular repair capacity at levels similar to hematological changes typically found in acute studies assaying for the lowest observed adverse effect level. These data suggest that individuals exposed to this ubiquitous air pollutant are likely to experience inflammation and vascular complications.

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