Burren R, Scaletta C, Frenk E, Panizzon R G, Applegate L A
Department of Dermatology, University Hospital, Lausanne, Switzerland.
Int J Cancer. 1998 Apr 13;76(2):201-6. doi: 10.1002/(sici)1097-0215(19980413)76:2<201::aid-ijc6>3.0.co;2-0.
DNA damage by UV radiation plays an essential role in skin cancer induction. We report that even sub-erythemal doses of solar simulating radiation, are capable of inducing substantial nuclear damage, namely pyrimidine dimers and p53 induction in human skin in situ. The quantity and distribution of p53 induced in human skin by UV radiation depended highly on the waveband and dose of UV used. Solar simulating radiation induced very high levels of p53 throughout all layers in epidermal keratinocytes 24 hr following an erythemal dose (230+/-15.9/1000 cells), and the induction followed a dose response. Following UVA I + II and UVA I radiations, p53 expression was approximately half of that seen with equivalent biological doses of solar simulating radiation (63.5+/-28.5 and 103+/-15.9, respectively). Expression of p53 was seen in basal cell keratinocytes at lower doses of UVA, but all layers of the epidermis were affected at higher doses. Pyrimidine dimer induction, however, was seen to be the same for equivalent biological doses of UVA I, UVA I + II and solar simulating radiations, which coincides with previous findings that pyrimidine dimers initiate the erythemal response and are implicated in skin carcinogenesis. When equivalent biological doses of pure UVA are used with no UVB contamination, significant nuclear alterations occur in human skin in situ, which can approach those seen with UVB radiation. Our results suggest that DNA damage assessed in vivo by immunohistochemistry could provide a very sensitive endpoint for determining the efficacy of protective measures, such as sunscreens or protective clothing, against both UVB- and UVA-induced damage in human skin.
紫外线辐射造成的DNA损伤在皮肤癌诱发过程中起着至关重要的作用。我们报告称，即使是低于红斑剂量的模拟太阳辐射，也能够在人体皮肤原位诱发大量的核损伤，即嘧啶二聚体和p53的诱导表达。紫外线辐射在人体皮肤中诱导产生的p53的数量和分布高度依赖于所使用紫外线的波段和剂量。在红斑剂量（230±15.9/1000个细胞）后的24小时，模拟太阳辐射在表皮角质形成细胞的所有层中诱导产生了非常高水平的p53，并且这种诱导呈现剂量反应关系。在UVA I + II和UVA I辐射后，p53的表达量约为同等生物剂量模拟太阳辐射所观察到的一半（分别为63.5±28.5和103±15.9）。在较低剂量的UVA照射下，基底细胞角质形成细胞中可见p53表达，但在较高剂量下，表皮的所有层均受到影响。然而，对于同等生物剂量的UVA I、UVA I + II和模拟太阳辐射，嘧啶二聚体的诱导情况是相同的，这与之前的研究结果一致，即嘧啶二聚体引发红斑反应并与皮肤癌发生有关。当使用无UVB污染的纯UVA同等生物剂量时，人体皮肤原位会发生显著的核改变，其程度可接近UVB辐射所观察到的情况。我们的结果表明通过免疫组织化学在体内评估DNA损伤可为确定防晒剂或防护服等防护措施对人体皮肤中UVB和UVA诱导损伤的防护效果提供一个非常敏感的终点指标。
