The multilayered organization of engineered human skin does not influence the formation of sunlight-induced cyclobutane pyrimidine dimers in cellular DNA

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 WE, 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-mn WC (which is not present in terrestrial sunlight) but, very unexpectedly, provides virtually no protection against environmentally relevant WE. 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.