Photodamage to Double-stranded DNA by Xanthone Analogues Increases Exponentially with Their HOMO Energies

DNA photodamage mediated by photosensitizers are believed to play an important role in solar UVA carcinogenesis. We investigated the relationship between the DNA-damaging abilities of photoexcited xanthone analogues (as photosensitizers) and their highest occupied molecular orbital (HOMO) energies. DNA damage was examined using /sup 32/P-labeled DNA fragments obtained from the p53 tumor suppressor gene. These compounds induced DNA photodamage in a similar manner, and the extents of DNA damage were following order: xanthone> thioxanthone > acridone. Photoexcited xanthone caused nucleobase oxidation specifically at 5'-G of GG sequence in double-stranded DNA. An oxidative product of 2'-deoxyguanosine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), was detected, and the amount was decreased by DNA denaturation. These findings suggest that photoexcited xanthone generates 8-OHdG at 5'-G of GG in double-stranded DNA through electron transfer. The calculated HOMO energies of these photosensitizers decreased in the following order: xanthone> thioxanthone > acridone. This study has demonstrated that DNA-damaging abilities of these photosensitizers increased exponentially with an increase in their HOMO energies.