Sequence-dependent variation in the reactivity of 8-oxo-7,8-dihydro- 2′-deoxyguanosine toward Oxidation

Kok Seong Lim, Koli Taghizadeh, John S. Wishnok, I. Ramesh Babu, Vladimir Shafirovich, Nicholas Geacintov, Peter C. Dedon

Research output: Contribution to journalArticle

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., et al. (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 (Figure presented) (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.

Original languageEnglish (US)
Pages (from-to)366-373
Number of pages8
JournalChemical Research in Toxicology
Volume25
Issue number2
DOIs
StatePublished - Feb 20 2012

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Oxidation
Riboflavin
Oxidants
Inflammation Mediators
Mutagenesis
Oligodeoxyribonucleotides
DNA sequences
Guanine
Charge transfer
Electrons
Mutation
8-oxo-7-hydrodeoxyguanosine
DNA
nitrosoperoxycarbonate

ASJC Scopus subject areas

  • Toxicology

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Sequence-dependent variation in the reactivity of 8-oxo-7,8-dihydro- 2′-deoxyguanosine toward Oxidation. / Lim, Kok Seong; Taghizadeh, Koli; Wishnok, John S.; Babu, I. Ramesh; Shafirovich, Vladimir; Geacintov, Nicholas; Dedon, Peter C.

In: Chemical Research in Toxicology, Vol. 25, No. 2, 20.02.2012, p. 366-373.

Research output: Contribution to journalArticle

Lim, Kok Seong ; Taghizadeh, Koli ; Wishnok, John S. ; Babu, I. Ramesh ; Shafirovich, Vladimir ; Geacintov, Nicholas ; Dedon, Peter C. / Sequence-dependent variation in the reactivity of 8-oxo-7,8-dihydro- 2′-deoxyguanosine toward Oxidation. In: Chemical Research in Toxicology. 2012 ; Vol. 25, No. 2. pp. 366-373.
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