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The Multilayered Organization of Engineered Human Skin Does Not Influence the Formation of Sunlight-induced Cyclobutane Pyrimidine Dimers in Cellular DNA¹

Departments of Medical Biology [J-P. T., R. D.] and Surgery [M. R.], Faculty of Medicine, Laval University, Quebec, Canada G1K 7P4; Unité de Recherche en Génétique Humaine et Moléculaire [J-P. T., R. D.] and Unité de Biotechnologie [M. R.], Centre de Recherche, CHUQ, Québec, Québec, Canada G1L 3L5; and Faculty of Medicine, Université de Montréal and Centre de Recherche Guy-Bernier, Hópital Maisonneuve-Rosemont, Montréal, Québec, Canada H1T 2M4 [E. A. D.]

Solar UVB initiates skin cancer mainly by generating highly premutagenic cyclobutane pyrimidine dimers (CPDs) and subsequent mutations in critical growth control genes. It is universally presumed that the upper epidermis in human skin blocks a significant portion of the incident UVB, thereby protecting the cancer-prone basal layer from CPD formation. Using two sensitive techniques for measuring CPD in cellular DNA, we confirmed that the multilayered organization of engineered human skin efficiently shields the basal layer against 254-nm UVC (which is not present in terrestrial sunlight) but, very unexpectedly, provides virtually no protection against environmentally relevant UVB. This underscores the importance of regular sunscreen use, which, in light of our data, may constitute a considerably more important first line of defense against photocarcinogenesis than previously believed.

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