title: Topical application of preparations containing DNA repair enzymes prevents ultraviolet-induced telomere shortening and c-FOS proto-oncogene hyperexpression in human skin: an experimental pilot study.
abstract: 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.
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
authors.forename: Velimir
authors.initials: V
authors.lastname: Altabas
authors.forename: Karmela
authors.initials: K
authors.lastname: Altabas
authors.forename: Enzo
authors.initials: E
authors.lastname: Berardesca
mesh_terms: D000328:Adult; D004247:DNA / Q000302:isolation & purification / Q000528:radiation effects; D045643:DNA Repair Enzymes / Q000008:administration & dosage / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000494:pharmacology; D004720:Endonucleases / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000528:radiation effects; D016762:Genes, fos / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D006801:Humans; D008081:Liposomes; D008297:Male; D010865:Pilot Projects; D000090063:Proto-Oncogene Mas; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013472:Sunlight; D013473:Sunscreening Agents / Q000494:pharmacology; D059506:Telomere Shortening / Q000187:drug effects* / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D008081:Liposomes; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D013473:Sunscreening Agents; D004247:DNA; D004720:Endonucleases; D004255:Deoxyribodipyrimidine Photo-Lyase; D045643:DNA Repair Enzymes