DNA oxidation has been investigated in the medium of cationic reverse micelles (RMs). The oxidative chemistry is photochemically initiated using the DNA intercalator bis(bipyridine)dipyridophenazine ruthenium(II) chloride ([Ru(bPY)(2)dPPZ]Cl-2) bound to duplex DNA in the RMs. High-resolution polyacrylamide gel electrophoresis (PAGE) is used to reveal and quantify guanine (G) oxidation products, including 8-oxo-7,8-dihydroguanine (80G). In buffer solution, the addition of the oxidative quenchers; potassium ferricyanicle or pentaamminechlorocobalt(III) dichloride leads to an increase in the amount of piperidine-labile G oxidation products generated via one-electron oxidation. In RMs, however, the yield of oxidatively generated damage is attenuated. With or without ferricyanide quencher in the RMs, the yield of oxidatively generated products is approximately the same. Inclusion of the cationic quencher [CoCl(NH3)(5)](2+) in the RIVIs increases the amount of oxidation products generated but not to the extent that it does in buffer solution. Under anaerobic conditions, all of the samples in RMs, with or without added oxidative quenchers, show decreased levels of piperidine-labile oxidation products, suggesting that the primary oxidant in RIVIs is singlet oxygen. G oxidation is enhanced in D2O and deuterated heptane and is diminished in the presence of sodium azide in RIVIs, also supporting O-1(2) as the main G oxidant in RMs. Isotopic labeling experiments show that the oxygen atom in 80G produced in RIVIs is not from water. The observed change in the G oxidation mechanism from a one-electron process in buffer to Mostly O-1(2) in RMs illustrates the importance of both DNA structure and DNA environment on the chemistry of G oxidation.