Sage E, Trabalzini L, Capozzi A, Conconi M T, Pastorini G, Tamaro M, Bordin F
Institut Curie, Paris, France.
J Photochem Photobiol B. 1991 Apr;9(1):43-59. doi: 10.1016/1011-1344(91)80003-z.
The photochemical and photobiological properties of 4,8-dimethyl-5'-acetylpsoralen (AcPso), proposed for the photochemotherapy of some skin diseases, were investigated. The photoreaction of AcPso with DNA is weaker in the presence of air than in a nitrogen atmosphere, in terms of total photobinding and DNA cross-linking; when UVA irradiation is performed in air, AcPso behaves as a monofunctional reagent. The quenching effect of oxygen is related to the high capacity of AcPso to produce singlet oxygen. Furthermore, it is demonstrated that AcPso photoadducts are better producers of singlet oxygen than free AcPso in solution. Using DNA sequencing methodology, two modes of DNA photosensitization by AcPso are shown, these lead to the formation of photoadducts mainly at T residues (and at C to a lesser extent) and to photo-oxidized G residues probably via singlet oxygen. Chemical or enzymatic cleavage were used as probes in these experiments. A rapid assay for the detection of the photodynamic effect of a photosensitizer on DNA, involving oxygen, is also described. Finally, the cytotoxicity and genotoxicity of AcPso on E. coli WP2 cells appear to be related to its ability to form photoadducts, in particular cross-links, rather than to its capacity to produce singlet oxygen.
对用于某些皮肤病光化学疗法的4,8 - 二甲基 - 5'- 乙酰基补骨脂素（AcPso）的光化学和光生物学性质进行了研究。就总的光结合和DNA交联而言，在空气中时AcPso与DNA的光反应比在氮气氛围中弱；当在空气中进行UVA照射时，AcPso表现为单功能试剂。氧的猝灭效应与AcPso产生单线态氧的高能力有关。此外，已证明在溶液中AcPso光加合物比游离的AcPso是更好的单线态氧产生剂。使用DNA测序方法，展示了AcPso对DNA的两种光致敏模式，这些模式主要导致在T残基处（以及在较小程度上在C处）形成光加合物，并可能通过单线态氧导致G残基的光氧化。在这些实验中使用化学或酶促切割作为探针。还描述了一种用于检测光敏剂对涉及氧的DNA的光动力效应的快速测定法。最后，AcPso对大肠杆菌WP2细胞的细胞毒性和遗传毒性似乎与其形成光加合物，特别是交联的能力有关，而不是与其产生单线态氧的能力有关。
