Sequence-Dependent Variation in the Reactivity of 8-Oxo-7,8-dihydro-2′-deoxyguanosine toward Oxidation
Author(s)Lim, Kok Seong; Taghizadeh, Koli; Wishnok, John S.; Babu, I. Ramesh; Shafirovich, Vladimir; Geacintov, Nicholas E.; Dedon, Peter C.; ... Show more Show less
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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.
Available in PMC 2013 February 20
DepartmentMassachusetts Institute of Technology. Center for Environmental Health Sciences; Massachusetts Institute of Technology. Department of Biological Engineering
Chemical Research in Toxicology
American Chemical Society
Lim, Kok Seong, Koli Taghizadeh, John S. Wishnok, I. Ramesh Babu, Vladimir Shafirovich, Nicholas E. Geacintov, and Peter C. Dedon. “Sequence-Dependent Variation in the Reactivity of 8-Oxo-7,8-Dihydro-2′-Deoxyguanosine Toward Oxidation.” Chemical Research in Toxicology 25, no. 2 (February 20, 2012): 366–373.
Author's final manuscript