title: Nicotine-modulated formation of spiroiminodihydantoin nucleoside via 8-oxo-7,8-dihydro-2'-deoxyguanosine in 2'-deoxyguanosine-hypochlorous acid reaction.
abstract: Hypochlorous acid (HOCl) is generated by myeloperoxidase of activated neutrophils which kill invading microorganisms, but also cause DNA damage in inflamed tissues. We report here that spiroiminodihydantoin nucleoside (dS), a further oxidized product of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), is formed, in addition to 8-chloro-2'-deoxyguanosine and 8-oxo-dG, by reaction of 2'-deoxyguanosine with HOCl. Presence of low concentrations of nicotine significantly enhanced the yields of these HOCl-modified nucleosides. Our results imply that nicotine may enhance genotoxicity and tissue damage caused by neutrophil activation. dS may also serve as a new biomarker for oxidative DNA damage induced by oxidants such as HOCl.
authors.affiliation: Unit of Endogenous Cancer Risk Factors, International Agency for Research on Cancer, 150 Cours Albert Thomas, F 69372 Cedex 08, Lyon, France.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohshima
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D013141:Spiro Compounds; C408822:spiroiminodihydantoin; D006151:Guanosine; D009538:Nicotine; D006997:Hypochlorous Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D009195:Peroxidase; D003849:Deoxyguanosine