TOXI 58 |
| Exocyclic adducts are mutagenic DNA lesions that have been associated with the processes of aging and carcinogenesis. Bifunctional alkylating agents, such as vinyl chloride and acrolein, react with deoxyguanosine producing, respectively, 1,N2-etheno-dG (1,N2-edG) and isomeric a-OH-1,N2-propano-dG (a-OH-PdG) and g-OH-1,N2-propano-dG (g-OH-PdG) adducts. Lipid peroxidation products also form these lesions. In spite of their chemical similarity, 1,N2-edG, a-OH-PdG and g-OH-PdG have different mutagenic properties and different repair mechanisms. We have prepared several DNA duplexes containing these lesions opposite, dC and dA residues, and determined their structure in solution using high-resolution NMR spectroscopy. Our studies show that these lesions are readily accommodated in right-handed duplexes, where they cause only local structural perturbations. In spite of this similarity, stabilization of the adduct-containing base pairs is remarkably different for each lesion. We will discuss the implications of these structures for processes of mutagenesis and DNA repair.
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Poster Presentations and Awards
6:00 PM-10:00 PM, Tuesday, 12 September 2006 Moscone Center -- Room 104, Poster
Sci-Mix
Division of Chemical Toxicology |
