Nitrogen dioxide as an oxidizing agent of 8-oxo-7,8-dihydro-2′-deoxyguanosine but not of 2′-deoxyguanosine

The redox reactions of guanine and its widely studied oxidation product, the 8-oxo-7,8-dihydro derivative, are of significant importance for understanding the mechanisms of oxidative damage in DNA. Employing 2'-deoxyguanosine 5'-monophospate (dGMP) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in neutral aqueous solutions as model systems, we have used nanosecond laser flash photolysis to demonstrate that neutral radicals, dGMP(-H)(.), derived by the one-electron oxidation and deprotonation of dGMP, can oxidize nitrite anions (NO2-) to the nitrogen dioxide radical (NO2)-N-.. In turn, we show that (NO2)-N-. can give rise to a one-electron oxidation of 8-oxo-G, but not of dGMP. The one-electron oxidation of dGMP was initiated by a radical cation generated by the laser pulse-induced photoionization of a pyrene derivative with enhanced water solubility, 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene (BPT). The dGMP(-H)(.) neutral radicals formed via deprotonation of the dGMP(.+) radical cations and identified by their characteristic transient absorption spectrum (lambda (max) similar to 310 nm) oxidize nitrite anions with a rate constant of (2.6 +/- 0.3) x 10(6) M-1 s(-1). The 8-oxo-dG is oxidized by (NO2)-N-. with a rate constant of (5.3 +/- 0.5) x 10(6) M-1 s(-1). The 8-oxo-dG(-H)(.) neutral radicals thus generated are clearly identified by their characteristic transient absorption spectra (lambda (max) similar to 320 nm). The rate constant of 8-oxo-dG oxidation (k(12)) by the (NO2)-N-. one-electron oxidant (the (NO2)-N-./NO2 redox potential, E degrees approximate to 1.04 V vs NHE) is lower than Kla for a series of oxidizing aromatic radical cations with known redox potentials. The hla values for 8-oxo-dG oxidation by different aromatic radical cations derived from the photoionization of their parent compounds depend on the redox potentials of the latter, which were in the range of 0.8-1.6 V versus NHE. The magnitude of kit gradually decreases from a value of 2.2 x 10(9) M-1 s(-1) (E degrees = 1.62 V) to 5.8 x 10(8) M-1 s(-1) (E degrees = 1.13 V) and eventually to 5 x 10(7) M-1 s(-1) (E degrees = 0.91 V). The implications of these results, including the possibility that the redox cycling of the (NO2)-N-./NO2- species can be involved in the further oxidative damage of 8-oxo-dG in DNA in cellular environments, are discussed.