Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation
Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation
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DOI：
10.1021/bi034593c
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发表时间：
2003-08-05
期刊：
影响因子：
2.9
通讯作者：
Sage, E
中科院分区：
文献类型：
--
作者：
Douki, T;Reynaud-Angelin, A;Sage, E
暴露于太阳紫外线辐射会引起可能导致皮肤癌的突变。UVA（320-340 nm）构成了太阳紫外线辐射的绝大部分，但在损伤DNA方面不如UVB（290 - 320 nm）有效。尽管UVA与光致癌作用有关，但其对阳光诱变的贡献尚未阐明，而且UVA产生的DNA损伤的特征仍然很差。我们采用HPLC-MS/MS和碱性琼脂糖凝胶电泳结合使用特定的DNA修复蛋白，以确定在中国仓鼠卵巢细胞暴露于纯UVA辐射，以及UVB和模拟阳光（λ> 295 nm）的各种类别和类型的DNA损伤，包括双嘧啶光产物的分布进行比较。在与人体暴露相容的UVA剂量下，氧化DNA损伤不是UVA诱导的主要损伤类型。事实上，单链断裂、氧化嘧啶、氧化嘌呤（基本上是8-氧代-7，8-二氢鸟嘌呤）和环丁烷嘧啶二聚体（CPD）以1：1：3：10的比例形成。此外，我们证明，在对比UVB和阳光，UVA产生的CPD与TT CPD，这强烈表明，它们是通过光敏三重态能量转移形成的一个大的优势。此外，UVA通过直接吸收既不诱导（6-4）光产物也不诱导其杜瓦异构体。我们还表明，UVA光子包含在阳光中，而不是UVB，涉及（6-4）光产物的光异构化，快速修复的损伤，到修复不良和高度致突变的杜瓦光产物。总之，我们的数据揭示了UVA的有害影响。
Exposure to solar UV radiation gives rise to mutations that may lead to skin cancer. UVA (320-340 nm) constitutes the large majority of solar UV radiation but is less effective than UVB (290320 nm) at damaging DNA. Although UVA has been implicated in photocarcinogenesis, its contribution to sunlight mutagenesis has not been elucidated, and DNA damage produced by UVA remains poorly characterized. We employed HPLC-MS/MS and alkaline agarose gel electrophoresis in conjunction with the use of specific DNA repair proteins to determine the distribution of the various classes and types of DNA lesions, including bipyrimidine photoproducts, in Chinese hamster ovary cells exposed to pure UVA radiation, as well as UVB and simulated sunlight (lambda > 295 nm) for comparison. At UVA doses compatible with human exposure, oxidative DNA lesions are not the major type of damage induced by UVA. Indeed, single-strand breaks, oxidized pyrimidines, oxidized purines (essentially 8-oxo-7,8-dihydroguanine), and cyclobutane pyrimidine dimers (CPDs) are formed in a 1: 1: 3: 10 ratio. In addition, we demonstrate that, in contrast to UVB and sunlight, UVA generates CPDs with a large predominance of TT CPDs, which strongly suggests that they are formed via a photosensitized triplet energy transfer. Moreover, UVA induces neither (6-4) photoproducts nor their Dewar isomers via direct absorption. We also show that UVA photons contained in sunlight, rather than UVB, are implicated in the photoisomerization of (6-4) photoproducts, a quickly repaired damage, into poorly repaired and highly mutagenic Dewar photoproducts. Altogether, our data shed new light on the deleterious effect of UVA.