Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation
Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation
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DOI：
10.1073/pnas.0604213103
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发表时间：
2006-09-12
影响因子：
11.1
通讯作者：
Douki, Thierry
中科院分区：
文献类型：
--
作者：
Mouret, Stephane;Baudouin, Caroline;Douki, Thierry
太阳紫外线辐射是皮肤癌发病机制中最重要的环境因素。众所周知的UVB辐射（290-320 nm）的遗传毒性主要涉及双嘧啶DNA光产物。相比之下，对皮肤中不被DNA直接吸收的更丰富的UVA辐射（320-400 nm）的贡献仍然知之甚少。使用一个高度准确和定量分析的基础上，HPLC与串联质谱法，我们确定了类型和产量的DNA损伤的形成在整个人体皮肤暴露于UVB或UVA。环丁烷嘧啶二聚体，一个典型的UVB诱导的DNA损伤，被发现产生显着的产量也在整个人类皮肤暴露于UVA通过不同的机制，由UVB引发。此外，后一类光产物的产生量大于8-氧代-7，8-二氢-2 ′-脱氧鸟苷，8-氧代-7，8-二氢-2 ′-脱氧鸟苷是人皮肤中最常见的氧化产生的损伤。引人注目的是，UVA产生的环丁烷嘧啶二聚体的去除率低于UVB照射皮肤产生的。最后，我们比较了DNA损伤的形成产率在整个皮肤中的角质形成细胞从相同的捐助者分离的原代培养物中确定的。因此，我们表明，人类皮肤有效地防止UVB诱导的DNA损伤，而对UVA的保护非常弱。这些观察结果强调了UVA诱导的DNA损伤在皮肤癌发生中可能发挥的作用，并应对光保护策略产生影响。
Solar UV radiation is the most important environmental factor involved in the pathogenesis of skin cancers. The well known genotoxic properties of UVB radiation (290-320 nm) mostly involve bipyrimidine DNA photoproducts. In contrast, the contribution of more-abundant UVA radiation (320-400 nm) that are not directly absorbed by DNA remains poorly understood in skin. Using a highly accurate and quantitative assay based on HPLC coupled with tandem mass spectrometry, we determined the type and the yield of formation of DNA damage in whole human skin exposed to UVB or UVA. Cyclobutane pyrimidine dimers, a typical UVB-induced DNA damage, were found to be produced in significant yield also in whole human skin exposed to UVA through a mechanism different from that triggered by UVB. Moreover, the latter class of photoproducts is produced in a larger amount than 8-oxo-7,8-dihydro-2'-deoxyguanosine, the most common oxidatively generated lesion, in human skin. Strikingly, the rate of removal of UVA-generated cyclobutane pyrimidine dimers was lower than those produced by UVB irradiation of skin. Finally, we compared the formation yields of DNA damage in whole skin with those determined in primary cultures of keratinocytes isolated from the same donors. We thus showed that human skin efficiently protects against UVB-induced DNA lesions, whereas very weak protection is afforded against UVA. These observations emphasize the likely role played by the UVA-induced DNA damage in skin carcinogenesis and should have consequences for photoprotection strategies.