DSM/INAC/SCIB UMR-E 3 CEA/UJF FRE CNRS 3200/Laboratoire Lésions des Acides Nucléiques, CEA-Grenoble, France.
Org Biomol Chem. 2010 Apr 7;8(7):1706-11. doi: 10.1039/b924712b. Epub 2010 Feb 4.
The carcinogenic action of UVA radiation is commonly attributed to DNA oxidation mediated by endogenous photosensitisers. Yet, it was recently shown that cyclobutane pyrimidine dimers (CPD), well known for their involvement in UVB genotoxicity, are produced in larger yield than oxidative lesions in UVA-irradiated cells and skin. In the present work, we gathered mechanistic information on this photoreaction by comparing formation of all possible bipyrimidine photoproducts upon UVA irradiation of cells, purified genomic DNA and dA(20):dT(20) oligonucleotide duplex. We observed that the distribution of photoproducts, characterized by the sole formation of CPD and the absence of (6-4) photoproducts was similar in the three types of samples. The CPD involving two thymines represented 90% of the amount of photoproducts. Moreover, the yields of formation of the DNA lesions were similar in cells and isolated DNA. In addition, the effect of the wavelength of the incident photons was found to be the same in isolated DNA and cells. This set of data shows that UVA-induced cyclobutane pyrimidine dimers are formed via a direct photochemical mechanism, without mediation of a cellular photosensitiser. This is possible because the double-stranded structure increases the capacity of DNA bases to absorb UVA photons, as evidenced in the case of the oligomer dA(20):dT(20). These results emphasize the need to consider UVA in the carcinogenic effects of sunlight. An efficient photoprotection is needed that can only be complete by completely blocking incident photons, rather than by systemic approaches such as antioxidant supplementation.
UVA 辐射的致癌作用通常归因于内源性光敏剂介导的 DNA 氧化。然而，最近的研究表明，环丁烷嘧啶二聚体（CPD），已知其参与 UVB 遗传毒性，在 UVA 照射的细胞和皮肤中产生的量比氧化损伤更大。在本工作中，我们通过比较细胞 UVA 照射时所有可能的双嘧啶光产物的形成、纯化基因组 DNA 和 dA(20):dT(20) 寡核苷酸双链，收集了这种光反应的机制信息。我们观察到，在三种类型的样品中，光产物的分布（特征是仅形成 CPD 和不存在（6-4）光产物）是相似的。涉及两个胸腺嘧啶的 CPD 代表光产物量的 90%。此外，在细胞和分离的 DNA 中，DNA 损伤的形成产率相似。此外，还发现入射光子波长的影响在分离的 DNA 和细胞中是相同的。这组数据表明，UVA 诱导的环丁烷嘧啶二聚体是通过直接光化学机制形成的，而不需要细胞光敏剂的介导。这是可能的，因为双链结构增加了 DNA 碱基吸收 UVA 光子的能力，正如寡核苷酸 dA(20):dT(20) 的情况所示。这些结果强调了需要考虑阳光中 UVA 的致癌作用。需要一种有效的光保护，这种保护只能通过完全阻挡入射光子来实现，而不是通过系统方法如抗氧化剂补充。
