The reaction of hydroxyl radical (OH') with DNA accounts for about half of radiation-induced DNA damage in living systems. Previous literature reports point out that the reaction of OH' with DNA proceeds mainly through the addition of OH to the C=C bonds of the DNA bases. However, recently it has been reported that the principal reaction of OH' with dGuo (deoxyguanosine) is the direct hydrogen atom abstraction from its exocyclic amine group rather than addition of OH' to the CC bonds. In the present work, these two reaction pathways of OH' attack on guanine (G) in the presence of water molecules (aqueous environment) are investigated using the density functional theory (DFT) B3LYP method with 6-31G* and 6-31++G** basis sets. The calculations show that the initial addition of the OH' at C4=C5 double bond of guanine is barrier free and the adduct radical (G-OH') has only a small activation barrier of L. 1-6 kcal/mol leading to the formation of a metastable ion-pair intermediate (G"---01-1-). The formation of ion-pair is a result of the highly oxidizing nature of the OH' in aqueous media. The resulting ion-pair (G"---01-1-) deprotonates to form H20 and neutral G radicals favoring G(Ni-H). with an activation barrier of ca. 5 kcal/mol. The overall process from the G(C4) -OH' (adduct) to G(Ni-H)' and water is found to be exothermic in nature by more than 13 kcal/mol. (G -OW), (13"----0H-.), and G(Ni-H)' were further characterized by the CAM-B3LYP calculations of their UV-vis spectra and good agreement between theory and experiment is achieved. Our calculations for the direct hydrogen abstraction pathway from N1 and N2 sites of guanine by the OH' show that this is also a competitive route to produce G(N2-H)', G(Ni-H)' and