COMPETITIVE REACTIONS OF PEROXYNITRITE WITH 2'-DEOXYGUANOSINE AND 7,8-DIHYDRO-8-OXO-2'-DEOXYGUANOSINE (8-OXODG) - RELEVANCE TO THE FORMATION OF 8-OXODG IN DNA EXPOSED TO PEROXYNITRITE

We have examined the formation of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) in reactions of peroxynitrite with 2'-deoxyguanosine (dG) an d calf-thymus DNA. Peroxynitrite reacts with dG at neutral pH, but thi s reaction does not result in the buildup of 8-oxodG. We also do not f ind any evidence for the formation of 8-oxodG in calf-thymus DNA upon exposure to peroxynitrite. When 8-oxodG is mixed with 1000-fold excess dG and then allowed to react with peroxynitrite, about 50% of the 8-o xodG is destroyed. The preferential reaction of 8-oxodG is also eviden t when dG in calf-thymus DNA is partially oxidized in an Udenfriend sy stem and then allowed to react with peroxynitrite. We suggest that 8-o xodG is not produced in peroxynitrite-mediated oxidations of dG and DN A or that it is produced but then is rapidly consumed in further react ions with peroxynitrite. Oxidized DNA bases frequently can be more oxi dation sensitive than their corresponding progenitors and, therefore, may be present at low steady-state concentrations and not represent st able markers of oxidative stress status. The importance of the 8-oxodG /peroxynitrite reaction is discussed in relation to the formation of m ore stable, secondary oxidation products that might be more useful mar kers of DNA damage.