TY - JOUR
T1 - Formation of spiroiminodihydantoin nucleoside by reaction of 8-oxo-7,8-dihydro-2′-deoxyguanosine with hypochlorous acid or a myeloperoxidase-H2O2-Cl- system
AU - Suzuki, T.
AU - Masuda, M.
AU - Friesen, M. D.
AU - Ohshima, H.
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Hypochlorous acid (HOCl), generated by myeloperoxidase from H2O2 and Cl-, is a strong chlorinating and oxidizing agent, playing an important role in host defense and inflammatory tissue injury. As several recent studies have shown that various oxidizing agents including peroxynitrite and singlet oxygen react readily with 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) to yield further oxidized products, we have studied the reaction of 8-oxodGuo with reagent HOCl and with a myeloperoxidase-H2O2-Cl- system. When 1 mM 8-oxodGuo was reacted with 0.5 mM HOCl at pH 7.4 and 37 °C, two major products were formed. They were identified as the diastereomers of spiroiminodihydantoin deoxyribonucleoside (dSph) on the basis of their identical ESI-MS and UV spectra and HPLC retention times with those of the major reaction products which were reported to be formed in other oxidation systems including potassium monopersulfate plus cobalt (II) chloride, peroxynitrite plus thiol, and type II photosensitization. Under the above reaction conditions, the yield of the diastereomers of dSph was 0.38 mM, with 0.57 mM 8-oxodGuo remaining unreacted. Since the presence of 50% D2O, 10 mM sodium azide, or 2% ethanol did not affect the yield of the products, involvement of singlet oxygen and hydroxyl radical in the formation of dSph from 8-oxodGuo with HOCl was ruled out. A 1000-fold excess of dGuo did not inhibit the reaction of 8-oxodGuo with HOCl, indicating that 8-oxodGuo reacts more readily than dGuo with HOCl. dSph was also formed by reaction of 8-oxodGuo with myeloperoxidase in the presence of H2O2 and Cl-. Our results suggest that formation of dSph from 8-oxodGuo is mediated, possibly via an addition of Cl+ to, or two-electron oxidation of 8-oxodGuo, with HOCl or the myeloperoxidase-H2O2-Cl- system.
AB - Hypochlorous acid (HOCl), generated by myeloperoxidase from H2O2 and Cl-, is a strong chlorinating and oxidizing agent, playing an important role in host defense and inflammatory tissue injury. As several recent studies have shown that various oxidizing agents including peroxynitrite and singlet oxygen react readily with 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) to yield further oxidized products, we have studied the reaction of 8-oxodGuo with reagent HOCl and with a myeloperoxidase-H2O2-Cl- system. When 1 mM 8-oxodGuo was reacted with 0.5 mM HOCl at pH 7.4 and 37 °C, two major products were formed. They were identified as the diastereomers of spiroiminodihydantoin deoxyribonucleoside (dSph) on the basis of their identical ESI-MS and UV spectra and HPLC retention times with those of the major reaction products which were reported to be formed in other oxidation systems including potassium monopersulfate plus cobalt (II) chloride, peroxynitrite plus thiol, and type II photosensitization. Under the above reaction conditions, the yield of the diastereomers of dSph was 0.38 mM, with 0.57 mM 8-oxodGuo remaining unreacted. Since the presence of 50% D2O, 10 mM sodium azide, or 2% ethanol did not affect the yield of the products, involvement of singlet oxygen and hydroxyl radical in the formation of dSph from 8-oxodGuo with HOCl was ruled out. A 1000-fold excess of dGuo did not inhibit the reaction of 8-oxodGuo with HOCl, indicating that 8-oxodGuo reacts more readily than dGuo with HOCl. dSph was also formed by reaction of 8-oxodGuo with myeloperoxidase in the presence of H2O2 and Cl-. Our results suggest that formation of dSph from 8-oxodGuo is mediated, possibly via an addition of Cl+ to, or two-electron oxidation of 8-oxodGuo, with HOCl or the myeloperoxidase-H2O2-Cl- system.
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U2 - 10.1021/tx010024z
DO - 10.1021/tx010024z
M3 - Article
C2 - 11559029
AN - SCOPUS:0034803009
SN - 0893-228X
VL - 14
SP - 1163
EP - 1169
JO - Chemical research in toxicology
JF - Chemical research in toxicology
IS - 9
ER -