Date of Award

2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cellular and Molecular Biology

College

College of Graduate Studies

First Advisor

Stephen Long

Second Advisor

Tracey Schock

Third Advisor

John Vena

Fourth Advisor

Gerard Hardiman

Fifth Advisor

Demetri Spyropoulos

Abstract

Mercury (Hg) is a ubiquitous environmental contaminant that is bioaccumulative and toxic. Ecosystems accumulate high mercury concentrations throughout their food web based on their unique environmental characteristics, exposing predators in these environments to mercury concentrations that elicit toxic effects, which are rarely observed outside of the laboratory. These predators provide the opportunity to investigate the sub-lethal effects of chronic mercury exposure that occur prior to the onset of toxic effects. Here the American alligator is thoroughly assessed for use as a sentinel of human dietary mercury exposure. We find that wild healthy alligators from the southeastern Atlantic coast of the US are exposed to mercury concentrations comparable to human populations with several different diets, and can be used as a sentinel for lifetime mercury exposure. The range of mercury concentrations that alligators are exposed to provide the opportunity to examine biochemical changes as sub-lethal effects, along an increasing mercury gradient. We observe that DNA methylation and mercury concentration are inversely correlated, but may be reversible based on diet. This epigenetic modification provides as assessment tool that can also be used for prevention in humans. To investigate underlying biochemical changes associated with increasing mercury exposure, a laboratory model of chronic exposure was assessed using an NMR based metabolomics approach. The diamondback terrapin, which is an established sentinel for mercury exposure, experienced both sub-lethal, and toxic effects, providing the opportunity to examine the onset of toxicity. We observed changes in small molecules involved in oxidative stress management throughout the range of mercury exposures, prior to toxic effects being observed. The terrapins experiencing toxic effects had behavioral changes commonly associated with mercury poisoning, such as neurological and muscular impairment. Many small molecules were altered in these terrapins, but most were related to their impaired foraging abilities. The Adverse Outcome Pathway (AOP) framework is used to put these data into a greater context that can be used for risk assessment for humans and wildlife. The AOP framework can be used for the prevention of toxicity, and a more complete understanding of the sub-lethal changes associated with this toxic contaminant.

Rights

All rights reserved. Copyright is held by the author.

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