title: Sequence-dependent variation in the reactivity of 8-Oxo-7,8-dihydro-2'-deoxyguanosine toward oxidation.
abstract: The goal of this study was to define the effect of DNA sequence on the reactivity of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) toward oxidation. To this end, we developed a quadrupole/time-of-flight (QTOF) mass spectrometric method to quantify the reactivity of site specifically modified oligodeoxyribonucleotides with two model oxidants: nitrosoperoxycarbonate (ONOOCO(2)(-)), a chemical mediator of inflammation, and photoactivated riboflavin, a classical one-electron oxidant widely studied in mutagenesis and charge transport in DNA. In contrast to previous observations with guanine [       Margolin  ,   Y.      ,     (  2006  )   Nat. Chem. Biol.  2  ,   365  ], sequence context did not affect the reactivity of ONOOCO(2)(-) with 8-oxodG, but photosensitized riboflavin showed a strong sequence preference in its reactivity with the following order (8-oxodG = O): COA ≈ AOG > GOG ≥ COT > TOC > AOC. That the COA context was the most reactive was unexpected and suggests a new sequence context where mutation hotspots might occur. These results point to both sequence- and agent-specific effects on 8-oxodG oxidation.
authors: Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States. kslim@mit.edu
authors: Kok Seong
authors: KS
authors: Lim
authors: Koli
authors: K
authors: Taghizadeh
authors: John S
authors: JS
authors: Wishnok
authors: I Ramesh
authors: IR
authors: Babu
authors: Vladimir
authors: V
authors: Shafirovich
authors: Nicholas E
authors: NE
authors: Geacintov
authors: Peter C
authors: PC
authors: Dedon
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D001483:Base Sequence; D002254:Carbonates / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000528:radiation effects; D009566:Nitrates / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry*; D010084:Oxidation-Reduction; D055668:Photochemical Processes; D017319:Photosensitizing Agents / Q000737:chemistry / Q000528:radiation effects; D012256:Riboflavin / Q000737:chemistry / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D002254:Carbonates; D009566:Nitrates; D016877:Oxidants; D017319:Photosensitizing Agents; C512272:nitrosoperoxycarbonate; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D012256:Riboflavin