Nicotine-modulated formation of spiroiminodihydantoin nucleoside via 8-oxo-7,8-dihydro-2'-deoxyguanosine in 2'-deoxyguanosine-hypochlorous acid reaction.

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.