Sequence-Dependent Variation in the Reactivity of 8-Oxo-7,8-dihydro-2'-deoxyguanosine toward Oxidation

• Main Authors: Lim, Kok Seong (Contributor), Taghizadeh, Koli (Contributor), Wishnok, John S. (Contributor), Babu, I. Ramesh (Contributor), Shafirovich, Vladimir (Author), Geacintov, Nicholas E. (Author), Dedon, Peter C. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Center for Environmental Health Sciences (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society, 2014-08-15T15:11:28Z.
• Subjects: Article
• Online Access: Get fulltext

Available in PMC 2013 February 20
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 (ONOOCO2-), 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 ONOOCO2- 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.
National Institute of Environmental Health Sciences (Bioanalytical Facilties Core of the MIT Center for Environmental Health Sciences (ES002109))
National Cancer Institute (U.S.) (CA026731)
National Cancer Institute (U.S.) (CA110261)