Formation of spiroiminodihydantoin nucleoside by reaction of 8-oxo-7,8-dihydro-2'-deoxyguanosine with hypochlorous acid or a myeloperoxidase-H(2)O(2)-Cl(-) system.
Hypochlorous acid (HOCl), generated by myeloperoxidase from H(2)O(2) 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-H(2)O(2)-Cl(-) system. When 1 mM 8-oxodGuo was reacted with 0.5 mM HOCl at pH 7.4 and 37 degrees 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% D(2)O, 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 H(2)O(2) 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-H(2)O(2)-Cl(-) system.
Suzuki
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Unit of Endogenous Cancer Risk Factors, International Agency for Research on Cancer, 69372 Lyon, Cedex 08, France.
Masuda
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Friesen
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MD
Ohshima
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H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002712:Chlorides / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D005609:Free Radicals; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006997:Hypochlorous Acid / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry*
D002712:Chlorides; D005609:Free Radicals; D016877:Oxidants; D013141:Spiro Compounds; C408822:spiroiminodihydantoin; D006151:Guanosine; D006997:Hypochlorous Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D009195:Peroxidase; D003849:Deoxyguanosine