INOR 149 |
| Metal-mediated oxidative DNA damage is the primary cause of cell death under conditions of oxidative stress and is an underlying cause of neurodegenerative and cardiovascular diseases, and cancer. Many studies of DNA damage prevention by antioxidants focus on enzymatic pathways involving decomposition of reactive oxygen species. Instead, we have been examining the ability of several potent and widely-studied classes of antioxidants to inhibit DNA damage by directly coordinating the iron and copper ions responsible for radical generation. Sulfur, selenium, and polyphenolic antioxidants prevent DNA damage through metal coordination at biologically-relevant, low micromolar concentrations. Polyphenolic antioxidants are very effective at preventing iron-mediated damage but much less effective at preventing copper-mediated damage, whereas the opposite is true for sulfur and selenium antioxidants. The metal-binding mechanism represents an important shift in thinking about antioxidant activity and has significant implications for future directions in development of antioxidant supplements and therapies. |
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Bioinorganic Chemistry: DNA and RNA
1:30 PM-5:30 PM, Sunday, August 19, 2007 BCEC -- 211, Oral
Division of Inorganic Chemistry |