Evaluation of Cutaneous Damage and Repair Following Acute Solar Ultraviolet Radiation Exposure: Experiments with an In Vitro Reconstructed Human Skin Model and Excised Human Skin

Overexposure of human skin to solar ultraviolet radiation (UVR) is known to produce deleterious effects including cutaneous photoaging and cancers. The present studies were conducted to confirm the utility of a commercially available full-thickness reconstructed human skin model (EpiDermFT) for reproducing tissue and cellular effects involved in cutaneous responses to acute solar UVR exposure. EpiDermFT tissues were irradiated with a single acute UVR dose approximately equivalent to either 6 or 9.5 minimal erythemal doses. Cutaneous damage and recovery were then monitored for a period of 7 days. Excised human skin specimens were treated under identical conditions for comparison. The UVR exposures resulted in pronounced structural and morphological alterations in both the EpiDermFT and excised skin tissues. Both models demonstrated a similar timecourse of sunburn cell (SBC) formation, epidermal necrosis, acantholysis and parakeratosis, and regeneration. The EpiDermFT model also reproduced key aspects of epidermal inflammation (interleukin-8 secretion), dermal matrix remodeling (active matrix metalloproteinase-1), DNA damage (cyclopyrimidine dimer [CPD] formation), and regenerative hyperplasia (Ki67) that have been implicated in pathogenesis of in vivo disease including skin photoaging and skin cancer. Quantitative evaluation of CPD formation revealed that the UVA component of solar UVR may be responsible for approximately 12.8% of UVR-induced cutaneous CPDs. Finally, the utility of a quantitative CPD ELISA for measuring CPD formation and sunscreen efficacy in the EpiDermFT model was demonstrated. These results provide further demonstration that in vitro reconstructed human skin are useful for human cutaneous photobiology studies related to UVR-induced photocarcingensis and photoaging, and evaluationof sunscreen DNA protection efficacy.

Photodamage, skin repair, ultraviolet exposure, EFT-400,  sunburn cells, epidermal necrosis, acantholysis,  parakeratosis, interleukin-8, cyclopyrimidine dimer formation, DNA damage, Ki67, photocarcingensis, photoaging, structural regeneration, morphological alterations, MMP-1

Solar radiation, UVA, UVB