Similar UV responses are seen in a skin organ culture as in human skin in vivo

Abstract: 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.

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