| Abstract: | Nitryl chloride and peroxynitrite are reactive nitrogen species generated by activated phagocytes against invading pathogens during infections and inflammation. In our previous report, formation of 8‐nitroxanthine and 8‐nitroguanine was observed in reaction of 2′‐deoxyguanosine or calf thymus DNA with nitryl chloride generated by mixing hypochlorous acid (HOCl) with nitrite (NC2?). The present study investigates factors control ling the yields of 8‐nitroxanthine and 8‐nitroguanine formation in nitration of 2′‐deoxyguanosine by nitryl chloride. We found that the yields of 8‐nitroxanthine and 8‐nitroguanine in reaction of 2′‐deoxyguanosine with nitryl chloride were highly dependent on the ratio of NO2? versus HOCl concentration. The yields of 8‐nitroxanthine and 8‐nitroguanine reached a plateau when the ratio of NC2? versus HOCl concentration was higher than 2. A possible mechanism was postulated to explain this observation. While 8‐nitroguanine is not stable in the presence of peroxynitrite, 8‐nitroxanthine is sensitive to HOCl. The stability of these two nitrated ad ducts might be a factor on their final yields in this reaction. Since HOCl is produced by neutrophils at sites of inflammation where the level of NC2? is elevated, it is conceivable that nitryl chloride contributes to DNA base nitration in vivo, forming 8‐nitroxanthine and 8‐nitroguanine. |
