Stevenson C, Davies R J
School of Biology and Biochemistry, Medical Biology Centre, Queen's University, Belfast BT9 7BL, Northern Ireland.
Chem Res Toxicol. 1999 Jan;12(1):38-45. doi: 10.1021/tx980158l.
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 2'-deoxyguanosine with PBSA in oxygenated solution generates the diagnostic compound 4, 8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine in comparatively high yield. In contrast, the main photoinduced cleavage sites in double-helical DNA are located at the 5'-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 riboflavin 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.
使用末端标记的合成寡脱氧核糖核苷酸进行的凝胶测序实验表明，2-苯基苯并咪唑（PBZ）和常见的防晒成分2-苯基苯并咪唑-5-磺酸（PBSA）在暴露于UV-B（290-320nm）辐射或自然阳光时，作为DNA损伤的有效光敏剂发挥作用。尽管这两种化合物都不与DNA特异性结合，但它们在亚毫摩尔浓度下都具有活性，并诱导形成哌啶不稳定的切割位点，这些位点几乎完全映射到鸟嘌呤残基的位置。对单链DNA的攻击模式，其中所有鸟嘌呤都被类似程度地修饰，是单线态氧光氧化的典型特征。单线态氧的参与与猝灭剂和清除剂对反应的影响一致，并且通过在含氧溶液中用PBSA对2'-脱氧鸟苷进行UV-B照射以相对高产率产生诊断化合物4,8-二氢-4-羟基-8-氧代-2'-脱氧鸟苷得到证实。相比之下，双螺旋DNA中的主要光诱导切割位点位于GG的5'-鸟嘌呤处以及（程度较小）GA双峰处。这种特征行为意味着从DNA到光激发敏化剂的电子转移是这种构象中的主要机制。对于核黄素和某些蝶呤衍生物，已经报道了对变性和天然DNA的类似反应二分法，这些衍生物在不紧密结合DNA方面类似于PBZ和PBSA。PBSA的光敏特性可能会降低其作为防晒剂的适用性。
