Photosensitized DNA damage participates in solar-UV
carcinogenesis, photogenotoxicity and
phototoxicity. A
chemoprevention of photosensitized DNA damage is one of the most important methods for the above phototoxic effects. In this study, the chemopreventive action of
xanthone (XAN) derivatives (
bellidifolin [BEL],
gentiacaulein [GEN], norswertianin [NOR] and
swerchirin [SWE]) on DNA damage photosensitized by
riboflavin was demonstrated using [32P]-5'-end-labeled
DNA fragments obtained from genes relevant to human
cancer. GEN and NOR effectively inhibited the formation of
piperidine-labile products at consecutive G residues by photoexcited
riboflavin, whereas BEL and SWE did not show significant inhibition of DNA damage. The four XAN derivatives decrease the formation of
8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), an oxidative product of G, by photoexcited
riboflavin. The preventive action for the
8-oxodGuo formation of these XAN derivatives increased in the following order: GEN>NOR>>BEL>SWE. A fluorescence spectroscopic study and ab initio molecular orbital calculations suggested that the prevention of
DNA photodamage is because of the quenching of the triplet excited state of
riboflavin by XAN derivatives through electron transfer. This
chemoprevention is based on neither antioxidation nor a physical
sunscreen effect; rather, it is based on the quenching of a
photosensitizer. In conclusion, XAN derivatives, especially GEN, may act as novel chemopreventive agents by the quenching mechanism of an excited
photosensitizer.