TY - JOUR
T1 - Novel products generated from 2′-deoxyguanosine by hypochlorous acid or a myeloperoxidase-H2O2-Cl-system
T2 - Identification of diimino-imidazole and amino-imidazolone nucleosides
AU - Suzuki, Toshinori
AU - Masuda, Mitsuharu
AU - Friesen, Marlin D.
AU - Fenet, Bernard
AU - Ohshima, Hiroshi
PY - 2002/6/1
Y1 - 2002/6/1
N2 - 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.
AB - 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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U2 - 10.1093/nar/30.11.2555
DO - 10.1093/nar/30.11.2555
M3 - Article
C2 - 12034845
AN - SCOPUS:0036606549
SN - 0305-1048
VL - 30
SP - 2555
EP - 2564
JO - Nucleic acids research
JF - Nucleic acids research
IS - 11
ER -