Document Type

Thesis

Date of Award

5-2007

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

MS in Environmental Toxicology

First Advisor

Bobby L. Wilson

Abstract

In the recent years of scientific investigation, the role of DNA in disease pathology has become increasingly important. In attempts to understand the effects of foreign materials and energies on DNA structures and interactions, several types of genetic damage have been characterized. One type of genetic malfunction that is of interest to this laboratory is oxidative damage to DNA. Oxidative damage can result when cells are exposed to stimuli such as metallic ions, creating free radicals from metabolic processes that can attack and damage cellular components such as DNA that lead to elevated levels of oxidative stress. The objective of this investigation was to examine the effects of various metallic members of the periodic table in relation to their ability to induce oxidative damage of a particular DNA constituent. Furthermore, any possible effect of time and temperature was examined via changes made to a standard reaction setup in attempts to understand the impact of these variables on the generation of the analyte of interest. The investigation into the effects of various metals on oxidative damage was monitored and assessed by means of HPLC analysis of 8-Hydroxy-2- 1 2 deoxyguanosine, a specific biomarker of oxidative stress. The metals of interest include iron, manganese, cobalt, copper, lead, chromium, nickel, cadmium, mercury, and zinc. The results of this study found iron to be by far the most potent inducer of oxidative damage followed by manganese, cobalt, chromium, copper, nickel, lead, and cadmium respectively. In relation to the time and temperature study, two general trends were -revcalcd that relate to an increase in temperature over time. Firstly, certain metals tend to exude an innate ability to increase or decrease the concentration of 8-0HdG detected :,:'0/ over time. Secondly, the effects of increased temperature on the outcomes of the aforementioned trends seem to only push these reactions further in the directions in which they were already compelled, causing either a noticeable nse or reduction tn concentration of 8-0HdG produced

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