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: Kok Seong Lim, Koli Taghizadeh, John S Wishnok, I Ramesh Babu, Vladimir Shafirovich, Nicholas E Geacintov, Peter C Dedon
• Journal: Chemical research in toxicology (Chem Res Toxicol) Vol. 25 Issue 2 Pg. 366-73 (Feb 20 2012) ISSN: 1520-5010 [Electronic] United States
• PMID: 22103813 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Carbonates
• Nitrates
• Oxidants
• Photosensitizing Agents
• nitrosoperoxycarbonate
• 8-Hydroxy-2'-Deoxyguanosine
• Deoxyguanosine
• Riboflavin

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Base Sequence
• Carbonates (chemistry)
• Deoxyguanosine (analogs & derivatives, chemistry, genetics, radiation effects)
• Nitrates (chemistry)
• Oxidants (chemistry)
• Oxidation-Reduction
• Photochemical Processes
• Photosensitizing Agents (chemistry, radiation effects)
• Riboflavin (chemistry, radiation effects)
• Ultraviolet Rays