Combination reactions of superoxide with 8-oxo-7,8-dihydroguanine radicals in DNA: Kinetics and end products

Richard Misiaszek, Yuriy Uvaydov, Conor Crean, Nicholas Geacintov, Vladimir Shafirovich

Research output: Contribution to journalArticle

Abstract

One of the major biomarkers of oxidative stress and oxidative damage of cellular DNA is 8-oxo-7,8-dihydroguanine (8-oxoGua), which is more easily oxidized than guanine to diverse oxidative products. In this work, we have investigated further oxidative transformations of 8-oxoGua in single- and double-stranded oligonucleotides to the dehydroguanidinohydantoin, oxaluric acid, and diastereomeric spiroiminodihydantoin lesions. The relative distributions of these end products were explored by a combined kinetic laser spectroscopy and mass spectrometry approach and are shown to depend markedly on the presence of superoxide radical anions. The 8-oxaGua radicals were produced by one-electron oxidation of 8-oxoGua by 2-aminopurine radicals generated by the two-photon ionization of 2-aminopurine residues site specifically positioned in 5′-d(CC[2-aminopurine]TC[8-oxoGua]CTACC). The hydrated electrons also formed in the photoionization process were trapped by dissolved molecular oxygen thus producing superoxide. A combination reaction between the 8-oxoGua and superoxide radicals occurs with the rate constant of (1.3 ± 0.2) × 108 M-1 S-1 and (1.0 ± 0.5) × 108 M-1 S-1 in single- and double-stranded DNA, respectively. The major end products of this reaction are the dehydroguanidinohydantoin lesions that slowly hydrolyze to oxaluric acid residues. In the presence of Cu,Zn-superoxide dismutase, an enzyme that induces the rapid catalytic dismutation of superoxide to the less reactive H 2O2 and O2, the yields of the dehydroguanidinohydantoin lesions become negligible. Under these conditions, the 8-oxoGua radicals do not exhibit any observable reactivities with oxygen (k < 102 M-1 S-1), decay on the time interval of several seconds, and the major reaction products are the spiroiminodihydantoin lesions. The possible biological implications of the 8-oxoGua oxidation are discussed.

Original languageEnglish (US)
Pages (from-to)6293-6300
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number8
DOIs
StatePublished - Feb 25 2005

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Superoxides
2-Aminopurine
Kinetics
DNA
Electrons
Oxygen
Oxidation
Photoionization
Laser spectroscopy
Oxidative stress
Molecular oxygen
Single-Stranded DNA
Guanine
Biomarkers
Dissolved oxygen
8-hydroxyguanine
Reaction products
Photons
Oligonucleotides
DNA Damage

ASJC Scopus subject areas

  • Biochemistry

Cite this

Combination reactions of superoxide with 8-oxo-7,8-dihydroguanine radicals in DNA : Kinetics and end products. / Misiaszek, Richard; Uvaydov, Yuriy; Crean, Conor; Geacintov, Nicholas; Shafirovich, Vladimir.

In: Journal of Biological Chemistry, Vol. 280, No. 8, 25.02.2005, p. 6293-6300.

Research output: Contribution to journalArticle

Misiaszek, Richard ; Uvaydov, Yuriy ; Crean, Conor ; Geacintov, Nicholas ; Shafirovich, Vladimir. / Combination reactions of superoxide with 8-oxo-7,8-dihydroguanine radicals in DNA : Kinetics and end products. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 8. pp. 6293-6300.
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