Date of Award
8-2010
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Legacy Department
Environmental Toxicology
Committee Chair/Advisor
Baldwin, William
Committee Member
Bain , Lisa
Committee Member
Rice , Charles
Committee Member
Watt , Paula
Committee Member
Klaine , Stephen
Abstract
The Constitutive Androstane Receptor (CAR) and the Pregnane X Receptor (PXR) are nuclear receptors of significant importance in the regulation of enzymes that metabolize, detoxify and eliminate compounds from the body. In this study we assessed the protective role of CAR and PXR in the basal and inducible regulation of Cytrochrome P450s (CYPs), and the potential of CAR and PXR to help protect individuals from the organophosphate, parathion and the plasticizer, nonylphenol, putatively due to improved metabolism and elimination. Knockout models of these receptors were used to model susceptible populations such as children that are known to have lower CAR and PXR expression during the first six months of age. A humanized model was used to extrapolate findings to human populations. Overall, the data suggests that individuals with low CAR or PXR (newborn children), or low CAR/PXR activation (elderly) may be more susceptible to xenobiotic toxicity putatively because of the lower expression of CAR and PXR resulting in a lower expression of CYPs which leads to the inability to metabolize, detoxify and eliminate toxic compounds.
Recommended Citation
Mota, Linda, "THE ROLE OF CAR AND PXR IN TOXICANT SENSITIVITY" (2010). All Dissertations. 593.
https://open.clemson.edu/all_dissertations/593