A recent experimental report on the suppression of the oxidative decomposition of guanines in deoxyribonucleic acid (DNA) double helices due to the attachment of a phenyl group to a guanine [Nakatani, K.; Dohno, C.; Saito, I. J. Am. Chem. Soc. 2002, 124, 6802] is examined by semiempirical Hartree-Fock (HF) molecular orbital (MO) calculations and ab initio HF MO calculations with the STO-3G basis set. Because of this attachment, the energy level of MO localized on the guanine shifts to lower energy in a vacuum, whereas it shifts to higher energy in water. This is mainly because the energy reduction of MO levels by the water solvent becomes smaller when the solvent molecules are excluded by the phenyl group. Consequently, a hole trap is enhanced at the phenylated guanine base in water. The observed suppression of the oxidative decomposition of guanines around the phenylated guanine is thus explained by considering the solvent effects. In addition, we have observed that energy shifts due to a benzyl group or a tert-butyl group are similar to those due to the phenyl group in our calculation.