Date of Award
Doctor of Philosophy (PhD)
Brumaghim, Julia L
Christensen , Kenneth A
Pennington , William T
McNeill , Jason
Inorganic selenium, oxo-sulfur, and polyphenol compounds are found in foods and dietary supplements, and are recognized for their nutritional benefits and their potential to treat or prevent diseases caused by oxidative stress. In our experiments to determine the effects of inorganic selenium compounds on iron-mediated DNA damage, Na2SeO33 and SeO2 exhibit antioxidant and pro-oxidant activities depending on concentrations of both the compound and hydrogen peroxide. Additional experiments demonstrate that iron coordination is a novel mechanism responsible for the observed activities. In similar experiments, oxo-sulfur compounds prevent Cu+/ H2O2-mediated DNA damage significantly more than DNA damage from Fe2+/H2O2. UV-vis and gel electrophoresis experiments also confirm that copper coordination is primarily responsible for the DNA damage inhibition, a novel mechanism that extends to all tested sulfur and selenium antioxidants. Electrospray ionization mass spectroscopy indicates that these sulfur and selenium compounds generally bind Cu + in a 1:1 ratio.
Combinations of bioactive components in foods can affect activity of antioxidants. For example, adding one equivalent of caffeine to polyphenols has no effect on DNA damage prevention by epigallocatechin gallate, but significantly decreases the antioxidant ability of quercetin. In addition, DNA damage prevention studies on peach extracts indicate that genetically-modified peach cultivars prevent more DNA damage than unmodified cultivars. In contrast, tetraphenyl-porphyrin-doped conjugated polymer dot nanoparticles cause DNA backbone and base damage upon irradiation, suggesting that these nanoparticles may be efficient photosensitizers for photodynamic therapy (PDT). Our studies also show H2O2 formation by and iron association with polyethylene glycol (PEG) and PEG-functionalized beads at biologically-relevant concentrations. Since Fe2+ and H2O2 react to form damaging hydroxyl radical, use of PEG-functionalized nanoparticles in medical applications may cause oxidative stress. Overall, this work has elucidated of antioxidant and pro-oxidant mechanisms of inorganic selenium, oxo-sulfur, and polyphenol compounds, as well as the potential toxicity of functionalized nanomaterials used for PDT and other medical applications.
Ramoutar, Ria, "UNDERSTANDING THE ANTIOXIDANT MECHANISM OF INORGANIC SELENIUM, OXO- SULFUR, AND POLYPHENOL COMPOUNDS, AND THE BIOLOGICAL IMPLICATIONS OF FUNCTIONALIZED NANOPARTICLES" (2009). All Dissertations. 430.