Novel products generated from 2′-deoxyguanosine by hypochlorous acid or a myeloperoxidase-H2O2-Cl-system: Identification of diimino-imidazole and amino-imidazolone nucleosides

Toshinori Suzuki, Mitsuharu Masuda, Marlin D. Friesen, Bernard Fenet, Hiroshi Ohshima

Research output: Contribution to journalArticle

Abstract

Hypochlorous acid (HOCl), generated by myeloperoxidase from H2O2 and Cl-, plays an important role in host defense and inflammatory tissue injury. We report here the identification of products generated from 2′-deoxyguanosine (dGuo) with HOCl. When 1 mM dGuo and 1 mM HOCl were reacted at pH 7.4 and 37°C for 15 min and the reaction was terminated with N-acetylcysteine (N-AcCys), two products were generated in addition to 8-chloro-2′-deoxyguanosine (8-Cl-dGuo). One was identified as an amino-imidazolone nucleoside (dlz), a previously reported product of dGuo with other oxidation systems. The other was identified as a novel diimino-imidazole nucleoside, and 2.4% 8-Cl-dGuo, with 61.5% unreacted dGuo. Precursors of dDiz and dlz containing a chlorine atom were found in the reaction solution in the absence of termination by N-AcCys. dDiz, dlz and 8-Cl-dGuo were also formed from the reaction of dGuo with myeloperoxidase in the presence of H2O2 and Cl- under mildly acidic conditions. These results imply that dDiz and dlz are generated from dGuo via chlorination by electrophilic attack of HOCl and subsequent dechlorination by N-AcCys. These products may play a role in cytotoxic and/or genotoxic effects of HOCl.

Original languageEnglish (US)
Pages (from-to)2555-2564
Number of pages10
JournalNucleic Acids Research
Volume30
Issue number11
StatePublished - Jun 1 2002
Externally publishedYes

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Hypochlorous Acid
Deoxyguanosine
Nucleosides
Peroxidase
Acetylcysteine
Halogenation
Chlorine
imidazolone
imidazole
Wounds and Injuries
8-chloro-2'-deoxyguanosine

ASJC Scopus subject areas

  • Genetics

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Novel products generated from 2′-deoxyguanosine by hypochlorous acid or a myeloperoxidase-H2O2-Cl-system : Identification of diimino-imidazole and amino-imidazolone nucleosides. / Suzuki, Toshinori; Masuda, Mitsuharu; Friesen, Marlin D.; Fenet, Bernard; Ohshima, Hiroshi.

In: Nucleic Acids Research, Vol. 30, No. 11, 01.06.2002, p. 2555-2564.

Research output: Contribution to journalArticle

Suzuki, Toshinori ; Masuda, Mitsuharu ; Friesen, Marlin D. ; Fenet, Bernard ; Ohshima, Hiroshi. / Novel products generated from 2′-deoxyguanosine by hypochlorous acid or a myeloperoxidase-H2O2-Cl-system : Identification of diimino-imidazole and amino-imidazolone nucleosides. In: Nucleic Acids Research. 2002 ; Vol. 30, No. 11. pp. 2555-2564.
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abstract = "Hypochlorous acid (HOCl), generated by myeloperoxidase from H2O2 and Cl-, plays an important role in host defense and inflammatory tissue injury. We report here the identification of products generated from 2′-deoxyguanosine (dGuo) with HOCl. When 1 mM dGuo and 1 mM HOCl were reacted at pH 7.4 and 37°C for 15 min and the reaction was terminated with N-acetylcysteine (N-AcCys), two products were generated in addition to 8-chloro-2′-deoxyguanosine (8-Cl-dGuo). One was identified as an amino-imidazolone nucleoside (dlz), a previously reported product of dGuo with other oxidation systems. The other was identified as a novel diimino-imidazole nucleoside, and 2.4{\%} 8-Cl-dGuo, with 61.5{\%} unreacted dGuo. Precursors of dDiz and dlz containing a chlorine atom were found in the reaction solution in the absence of termination by N-AcCys. dDiz, dlz and 8-Cl-dGuo were also formed from the reaction of dGuo with myeloperoxidase in the presence of H2O2 and Cl- under mildly acidic conditions. These results imply that dDiz and dlz are generated from dGuo via chlorination by electrophilic attack of HOCl and subsequent dechlorination by N-AcCys. These products may play a role in cytotoxic and/or genotoxic effects of HOCl.",
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