Photosensitization of Guanine-Specific DNA Damage by 2-Phenylbenzimidazole and the Sunscreen Agent 2-Phenylbenzimidazole-5-sulfonic Acid

Gel sequencing experiments with end-labeled synthetic oligodeoxyribonucleotides have established that 2-phenylbenzimidazole (PBZ) and the common sunscreen constituent 2-phenylbenzimidazole-5-sulfonic acid (PBSA) function as efficient photosensitizers of DNA damage when they are exposed to UV-B (290-320 nm) radiation or natural sunlight. Although neither compound binds specifically to DNA, both are active at sub-millimolar concentrations and induce the formation of piperidine-labile cleavage sites that map almost exclusively to the positions of guanine residues. The pattern of attack on single-stranded DNA, where all guanines are modified to a similar extent, is typical of photooxidation by singlet oxygen. The involvement of singlet oxygen is consistent with the effect of-quenchers and scavengers on the reaction, and is supported by the demonstration that UV-B irradiation of 2ʹ-deoxyguanosine with PBSA in oxygenated solution generates the diagnostic compound 4,8-dihydro-4-hydroxy-8-oxo-2ʹ-deoxyguanosine in comparatively high yield. In contrast, the main photoinduced cleavage sites in double-helical DNA are located at the 5ʹ-guanines of GG and (to a lesser degree) GA doublets. This characteristic behavior implies that electron transfer from DNA to the photoexcited sensitizer is the predominant mechanism in this conformation. A similar dichotomy of reactivity toward denatured and native DNA has been reported for ribofiavin and certain pterin derivatives which resemble PBZ and PBSA in not binding tightly to DNA. The photosensitizing properties of PBSA could possibly detract from its fitness as a sunscreen agent.