Similar UV responses are seen in a skin organ culture as in human skin in vivo.
Ultraviolet radiation (UVR) plays an important role in the development of non-melanoma skin cancer. Most tumors develop in chronically sun-exposed skin, most often in cosmetically sensitive locations, where in vivo experiments may be difficult to perform. In this study, we describe a skin organ culture model with preserved normal morphology and intact response to UVR. Skin explants from chronically sun-exposed and non-sun-exposed skin were irradiated with artificial UVA+UVB with and without topical sunscreen. UV-induced DNA damage, epidermal p53 response and repair kinetics were analyzed using immunohistochemistry. Four hours after UV-irradiation epidermal keratinocytes showed a strong immunoreactivity for thymine-dimers. Gradual repair during an incubation time resulted in few residual thymine-dimers after 48 h. Repair appeared to be more efficient in chronically sun-exposed skin compared with non-sun-exposed skin. There was also an accumulation of p53 protein in epidermal keratinocytes, peaking at 4-24 h after irradiation. Large interindividual differences with respect to formation and repair of thymine-dimers as well as induction and duration of the p53 response were observed. Skin explants treated with topical sunscreen prior to UV-irradiation showed a clear reduction of thymine-dimers and p53 expression. The epidermal UV-responses and repair kinetics in organ-cultured skin were similar to what was found in vivo. Our data suggest that organ-cultured skin provides a valuable tool for studies of UV-induced epidermal responses in chronically sun-exposed skin.
Department of Genetics and Pathology, University Hospital, S-751 85 Uppsala, Sweden.
Helena
H
Bäckvall
Cecilia
C
Wassberg
Berit
B
Berne
Fredrik
F
Ponten
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D009924:Organ Culture Techniques; D011740:Pyrimidine Dimers / Q000378:metabolism / Q000528:radiation effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology; D013473:Sunscreening Agents / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D011740:Pyrimidine Dimers; D013473:Sunscreening Agents; D016159:Tumor Suppressor Protein p53