TY - JOUR
T1 - Sequence-dependent variation in the reactivity of 8-oxo-7,8-dihydro- 2′-deoxyguanosine toward Oxidation
AU - Lim, Kok Seong
AU - Taghizadeh, Koli
AU - Wishnok, John S.
AU - Babu, I. Ramesh
AU - Shafirovich, Vladimir
AU - Geacintov, Nicholas E.
AU - Dedon, Peter C.
PY - 2012/2/20
Y1 - 2012/2/20
N2 - 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.
AB - 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.
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U2 - 10.1021/tx200422g
DO - 10.1021/tx200422g
M3 - Article
C2 - 22103813
AN - SCOPUS:84858120472
SN - 0893-228X
VL - 25
SP - 366
EP - 373
JO - Chemical research in toxicology
JF - Chemical research in toxicology
IS - 2
ER -