Photosensitization of guanine-specific DNA damage by 2-phenylbenzimidazoleand the sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid

Gel sequencing experiments with end-labeled synthetic oligodeoxyribonucleot ides have established that 2-phenylbenzimidazole (PBZ) and the common sunsc reen constituent 2-phenylbenzimidazole-5-sulfonic acid (PBSA) function as e fficient photosensitizers of DNA damage when they are exposed to UV-B (290- 320 nm) radiation or natural sunlight. Although neither compound binds spec ifically to DNA, both are active at sub-millimolar concentrations and induc e the formation of piperidine-labile cleavage sites that map almost exclusi vely to the positions of guanine residues. The pattern of attack on single- stranded DNA, where all guanines are modified to a similar extent, is typic al of photooxidation by singlet oxygen. The involvement of singlet oxygen i s consistent with the effect of quenchers and scavengers on the reaction, a nd is supported by the demonstration that W-B irradiation of 2'-deoxyguanos ine with PBSA in oxygenated solution generates the diagnostic compound 4,8- dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine in comparatively high yield. In c ontrast, the main photoinduced cleavage sites in double-helical DNA are loc ated at the 5'-guanines of GG and (to a lesser degree) GA doublets. This ch aracteristic behavior implies that electron transfer from DNA to the photoe xcited sensitizer is the predominant mechanism in this conformation. A simi lar dichotomy of reactivity toward denatured and native DNA has been report ed for riboflavin and certain pterin derivatives which resemble PBZ and PBS A in not binding tightly to DNA. The photosensitizing properties of PBSA co uld possibly detract from its fitness as a sunscreen agent.