TOXI 115 |
| Deamination of DNA bases occurs by both chemical and enzymatic mechanisms, including nitrosation reactions with derivatives of nitric oxide. Significant controversy surrounds the nitrosative deamination of 2¢-deoxyguanosine (dG), with evidence for the formation of both 2¢-deoxyxanthosine (dX) and 2¢-deoxyoxanosine (dO) under acidic conditions but only dX under conditions of biological pH. We have been unable to detect dO at a level of >1 per 107 nt in isolated DNA exposed to biologically relevant levels of nitrous anhydride, an NO-derived nitrosating species, or in E. coli, cultured mammalian cells or tissues from mouse models of inflammation. To test a recent model of base-pairing influences on dO formation, we have used an NO/O2 delivery system and a sensitive LC/MS-MS method to quantify the formation of dX and dO from dG as a free nucleoside and in single- and double-stranded oligonucleotides. The results shed light on the biological relevance of dO as a product of nitrosative deamination of dG. |
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Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster
Division of Chemical Toxicology |