Oxidation of 8-Oxo-7,8-dihydro-2′-deoxyguanosine by Oxyl Radicals Produced by Photolysis of Azo Compounds

Jie Shao, Nicholas Geacintov, Vladimir Shafirovich

Research output: Contribution to journalArticle

Abstract

Oxidative damage to 8-oxo-7,8-dihydroguanine (8-oxoG) bases initiated by photolysis of the water-soluble radical generator 2,2′-azobis(2- amidinopropane) dihydrochloride (AAPH) has been investigated by laser kinetic spectroscopy. In neutral oxygenated aqueous solutions, 355 nm photolysis of AAPH initiates efficient one-electron oxidation of the 8-oxodG nucleosides directly monitored by the appearance of the 8-oxodG•++/8-oxodG(-H) •+ radicals at 325 nm. The reaction kinetics consist of a mechanism that includes the transformation of the 2-amidinoprop-2-peroxyl radicals (ROO•+) derived from photolysis of AAPH to more reactive 2-amidinoprop-2-oxyl radicals (RO•+), which directly react with the 8-oxoG bases. The major pathways for the formation of end products of 8-oxoG oxidation include the combination of the 8-oxodG •++/8-oxodG(-H)•+ radicals with superoxide (O2 •+-) and ROO•+ radicals in approximately 1:1 ratios, as demonstrated by experiments with Cu,Zn superoxide dismutase, to form dehydroguanidinohydantoin (Ghox) derivatives. This mechanism was confirmed by analysis of the end products produced by the oxidation of two substrates: (1) the 8-oxoG derivative 2′,3′, 5′-tri-O-acetyl-7,8-dihydroguanosine (tri-O-Ac-8-oxoG) and (2) the 5′-d(CCATC[8-oxoG]CTACC) sequence. The major products isolated by HPLC and identified by mass spectrometry methods were the tri-O-Ac-Ghox and 5′-d(CCATC[Ghox]CTACC products.

Original languageEnglish (US)
Pages (from-to)933-938
Number of pages6
JournalChemical Research in Toxicology
Volume23
Issue number5
DOIs
StatePublished - May 17 2010

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Azo Compounds
Photolysis
Oxidation
Derivatives
Nucleosides
Reaction kinetics
Superoxides
Mass spectrometry
8-oxo-7-hydrodeoxyguanosine
8-hydroxyguanine
Mass Spectrometry
Spectrum Analysis
Lasers
High Pressure Liquid Chromatography
Spectroscopy
Electrons
Kinetics
Water
Substrates

ASJC Scopus subject areas

  • Toxicology

Cite this

Oxidation of 8-Oxo-7,8-dihydro-2′-deoxyguanosine by Oxyl Radicals Produced by Photolysis of Azo Compounds. / Shao, Jie; Geacintov, Nicholas; Shafirovich, Vladimir.

In: Chemical Research in Toxicology, Vol. 23, No. 5, 17.05.2010, p. 933-938.

Research output: Contribution to journalArticle

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title = "Oxidation of 8-Oxo-7,8-dihydro-2′-deoxyguanosine by Oxyl Radicals Produced by Photolysis of Azo Compounds",
abstract = "Oxidative damage to 8-oxo-7,8-dihydroguanine (8-oxoG) bases initiated by photolysis of the water-soluble radical generator 2,2′-azobis(2- amidinopropane) dihydrochloride (AAPH) has been investigated by laser kinetic spectroscopy. In neutral oxygenated aqueous solutions, 355 nm photolysis of AAPH initiates efficient one-electron oxidation of the 8-oxodG nucleosides directly monitored by the appearance of the 8-oxodG•++/8-oxodG(-H) •+ radicals at 325 nm. The reaction kinetics consist of a mechanism that includes the transformation of the 2-amidinoprop-2-peroxyl radicals (ROO•+) derived from photolysis of AAPH to more reactive 2-amidinoprop-2-oxyl radicals (RO•+), which directly react with the 8-oxoG bases. The major pathways for the formation of end products of 8-oxoG oxidation include the combination of the 8-oxodG •++/8-oxodG(-H)•+ radicals with superoxide (O2 •+-) and ROO•+ radicals in approximately 1:1 ratios, as demonstrated by experiments with Cu,Zn superoxide dismutase, to form dehydroguanidinohydantoin (Ghox) derivatives. This mechanism was confirmed by analysis of the end products produced by the oxidation of two substrates: (1) the 8-oxoG derivative 2′,3′, 5′-tri-O-acetyl-7,8-dihydroguanosine (tri-O-Ac-8-oxoG) and (2) the 5′-d(CCATC[8-oxoG]CTACC) sequence. The major products isolated by HPLC and identified by mass spectrometry methods were the tri-O-Ac-Ghox and 5′-d(CCATC[Ghox]CTACC products.",
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AB - Oxidative damage to 8-oxo-7,8-dihydroguanine (8-oxoG) bases initiated by photolysis of the water-soluble radical generator 2,2′-azobis(2- amidinopropane) dihydrochloride (AAPH) has been investigated by laser kinetic spectroscopy. In neutral oxygenated aqueous solutions, 355 nm photolysis of AAPH initiates efficient one-electron oxidation of the 8-oxodG nucleosides directly monitored by the appearance of the 8-oxodG•++/8-oxodG(-H) •+ radicals at 325 nm. The reaction kinetics consist of a mechanism that includes the transformation of the 2-amidinoprop-2-peroxyl radicals (ROO•+) derived from photolysis of AAPH to more reactive 2-amidinoprop-2-oxyl radicals (RO•+), which directly react with the 8-oxoG bases. The major pathways for the formation of end products of 8-oxoG oxidation include the combination of the 8-oxodG •++/8-oxodG(-H)•+ radicals with superoxide (O2 •+-) and ROO•+ radicals in approximately 1:1 ratios, as demonstrated by experiments with Cu,Zn superoxide dismutase, to form dehydroguanidinohydantoin (Ghox) derivatives. This mechanism was confirmed by analysis of the end products produced by the oxidation of two substrates: (1) the 8-oxoG derivative 2′,3′, 5′-tri-O-acetyl-7,8-dihydroguanosine (tri-O-Ac-8-oxoG) and (2) the 5′-d(CCATC[8-oxoG]CTACC) sequence. The major products isolated by HPLC and identified by mass spectrometry methods were the tri-O-Ac-Ghox and 5′-d(CCATC[Ghox]CTACC products.

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