A significant focus of nucleic acids research is on the reactivity of electrophilic species with DNA to form addition products (adducts). Phenols are known to be able to form adducts at the C8 site of deoxyguanosine (dG). This dissertation studies the oxygen (O)-linked class of phenolic dG adducts for their hydrolytic stability as well as their structural impact on the DNA duplex. To determine the effect of C8 O-linked phenolic dG adducts on glycosidic bond stability spectrophotometric determination of hydrolysis kinetics was performed. The kinetics establish the adducts to be less stable than native dG in acid, but surprisingly stable under physiological conditions. Then to assess the modified duplex structure, a C8 O-linked phenolic dG adduct was incorporated into a DNA duplex. Thermal melting analysis establish the adduct as having a destabilizing effect on the regularly paired duplex and the conformational analysis suggests the phenolic lesion to be weakly mutagenic. / NSERC
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OGU.10214/6760 |
| Date | 17 May 2013 |
| Creators | Kuska, Michael S. |
| Contributors | Manderville, Richard A. |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Rights | Attribution-NoDerivs 2.5 Canada, http://creativecommons.org/licenses/by-nd/2.5/ca/ |
Page generated in 0.002 seconds