New Insights into the Reaction Paths of Hydroxyl Radicals with 2′-Deoxyguanosine

The reaction of HO(center dot) radical with 2'-deoxyguanosine is intensively studied as a model for DNA damage. Several aspects related to the reaction paths responsible for the most relevant lesions are not well understood. We have reinvestigated the reaction of HO(center dot) with 2'-deoxyguanosine by pulse radiolysis and extended our studies to a variety of substituted derivatives. The main path of hydrogen abstraction was confirmed to be from the exocyclic NH(2) group, followed by a water-assisted tautomerization. The rate constant (k = 2.3 x 10(4) s(-1)) obtained from the spectral changes at 620 rim is influenced by the substituent at the C8 position. When N1-H is replaced by N1-CH(3), the tautomerization does not occur. The spectral changes at 370 nm that correspond to a rate constant of 6.9 x 10(5) s(-1) were assigned to the cyclization of 2'-deoxyguanosin-5'-yl radical with formation of 5',8-cyclo-2'-deoxyguanosine as the product. When NEt(2) replaces the exocyclic NH(2), the spectral changes at all wavelengths follow second-order kinetics, suggesting a slow ring-opening of the 8-hydroxyl adduct of 2'-deoxyguanosine.