Emanuele Enzo, Altabas Velimir, Altabas Karmela, Berardesca Enzo
J Drugs Dermatol. 2013 Sep;12(9):1017-21.
The exposure to ultraviolet radiation (UVR) is one of the most important risk factors for skin aging and increases the risk of malignant transformation. Telomere shortening and an altered expression of the proto-oncogene c-FOS are among the key molecular mechanisms associated with photoaging and tumorigenesis. Photolyase from A. nidulans and endonuclease from M. luteus are xenogenic DNA repair enzymes which can reverse the molecular events associated with skin aging and carcinogenosis caused by UVR exposure. Therefore, the purpose of this study was to investigate whether the topical application of preparations containing DNA repair enzymes may prevent UVR-induced acute telomere shortening and FOS gene hyperexpression in human skin biopsies. Twelve volunteers (Fitzpatrick skin types I and II) were enrolled for this experimental study, and six circular areas (10 mm diameter) were marked out on the nonexposed lower back of each participant. One site was left untreated (site 1: negative control), whereas the remaining five sites (designated sites 2-6) were exposed to solar-simulated UVR at 3 times the MED on four consecutive days. Site 2 received UVR only (site 2: positive control), whereas the following products were applied to sites 3-6, respectively: vehicle (moisturizer base cream; applied both 30 minutes before and immediately after each irradiation; site 3); a traditional sunscreen (SS, SPF 50) 30 minutes before irradiation and a vehicle immediately after irradiation (site 4); a SS 30 minutes before irradiation and an endonuclease preparation immediately after irradiation (site 5); a SS plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation (site 6). Skin biopsies were taken 24 h after the last irradiation. The degree of telomere shortening and c-FOS gene expression were measured in all specimens. Strikingly, the combined use of a SS plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation completely abrogated telomere shortening and c-FOS gene hyperexpression induced by the experimental irradiations. We conclude that the topical application of preparations containing both photolyase from A. nidulans and endonuclease from M. luteus may be clinically useful to prevent skin aging and carcinogenesis by abrogating UVR-induced telomere shortening and c-FOS gene hyperexpression.
紫外线辐射（UVR）暴露是皮肤衰老的最重要风险因素之一，且会增加恶性转化的风险。端粒缩短和原癌基因c-FOS表达改变是与光老化和肿瘤发生相关的关键分子机制。构巢曲霉的光解酶和藤黄微球菌的核酸内切酶是异种DNA修复酶，它们可以逆转与UVR暴露引起的皮肤衰老和癌变相关的分子事件。因此，本研究的目的是调查局部应用含DNA修复酶的制剂是否可以预防UVR诱导的人体皮肤活检中端粒急性缩短和FOS基因过度表达。12名志愿者（Fitzpatrick皮肤类型I和II）参与了本实验研究，在每位参与者未暴露的下背部标记出6个圆形区域（直径10毫米）。一个部位不做处理（部位1：阴性对照），而其余5个部位（指定为部位2 - 6）连续4天接受相当于最小红斑量（MED）3倍的模拟阳光UVR照射。部位2仅接受UVR照射（部位2：阳性对照），而以下产品分别应用于部位3 - 6：赋形剂（保湿基础霜；在每次照射前30分钟和照射后立即涂抹；部位3）；传统防晒霜（SS，SPF 50），照射前30分钟涂抹，照射后立即涂抹赋形剂（部位4）；照射前30分钟涂抹SS，照射后立即涂抹核酸内切酶制剂（部位5）；照射前30分钟涂抹SS加光解酶，照射后立即涂抹核酸内切酶制剂（部位6）。在最后一次照射后24小时采集皮肤活检样本。测量所有样本中端粒缩短程度和c-FOS基因表达。令人惊讶的是，照射前30分钟联合使用SS加光解酶以及照射后立即使用核酸内切酶制剂完全消除了实验照射诱导的端粒缩短和c-FOS基因过度表达。我们得出结论，局部应用含构巢曲霉光解酶和藤黄微球菌核酸内切酶的制剂可能在临床上有助于通过消除UVR诱导的端粒缩短和c-FOS基因过度表达来预防皮肤衰老和癌变。
