TOXI 84 |
| DNA damage resulting from oxidative stress has been strongly associated with cancer, chronic degenerative diseases and aging. While both deoxyribose and nucleobase moieties in DNA are targets for oxidation, our research has focused on guanine as the most frequently oxidized base because of its low ionization potential. We have previously determined that nitrosoperoxycarbonate, a chemical mediator of inflammation, preferentially oxidizes guanines in 5'-GC-3' sequences that are characterized by the highest ionization potentials, while a highly reactive hydroxyl radical, a product of Fe2+-EDTA complex-mediated Fenton reaction or of -irradiation of an aqueous solution, is equally reactive with guanines in all sequence contexts. Taken together, these results indicate that factors other than electron transfer can determine the extent and location of guanine oxidation in DNA. To further investigate these factors, we define the role of Fe2+ binding in altering sequence-selective guanine oxidation mediated by the Fenton reaction in double-stranded DNA using sequencing gel methods. To determine the effect of sequence context on reactivity of a guanine radical cation, an intermediate in the guanine oxidation reaction, we compare the distributions of oxidative lesions produced within different sequence contexts by liquid chromatography and mass spectrometry techniques. |
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Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster
Sci-Mix
Division of Chemical Toxicology |