HUMAN SKIN EQUIVALENT: A RELIABLE IN VITRO MODEL FOR CARCINOGENIC EXPERIMENTS.

EpiDermFT (MatTek Co., MA) is an in vitro model for human skin derived from keratinocytes of human neonatal foreskin. The epidermal component is cultured to form a highly differentiated model of metabolically and mitotically active cells that are arranged analogous to those found in human epidermal skin. This advanced full-thickness model incorporates a fibroblast-containing dermis with epidermal keratinocytes. EpiDerm has been used in dermatological research to test the irritancy of various consumer products, and the reactivity of specific biomarkers. In this study, researchers in the Dept. of Dermatology, Mount Sinai School of Medicine (NY) evaluated the capacity of this human skin equivalent to express cyclobutane-pyrimidine dimer (CPD) and Proliferating Cell Nuclear Antigen (PCNA) using immunohistochemical analysis. CPD represents one of the most abundant mutagenic and cytotoxic DNA photoproduct lesions, and current literature supports this biomarker’s reliability in assessing ultraviolet-induced cutaneous DNA damage in human skin. PCNA is an active nuclear protein involved in cellular proliferation and repair that can be used indirectly to assess damage to cutaneous cellular mechanics. This report is the first to describe the immunohistochemical expression profiles of these biomarkers in human reconstituted skin. The Mount Sinai School of Medicine researchers observed a dose dependent increase in CPD expression from 20 mJ/m2 to 60 mJ/m2 of UVB for EpiDerm specimens harvested six hours post-irradiation, with no CPD immunoreactivity in sham radiation specimens. PCNA expression was noted throughout sham radiation control specimens, with subsequent diminished expression upon ultraviolet exposure from 20 mJ/m2 to 60 mJ/m2, consistent with our previously reported results with similar UVB exposure levels in mouse skin. All specimens showed disrupted architecture at 100 mJ/m2. The researchers concluded that EpiDermFT represents a formidable alternative to human and animal skin models. This viable in vitro option offers compelling relevance in the elucidation of ultraviolet induced biomarker evaluation and stands to serve as a suitable substitute in cutaneous carcinogenesis experimentation.

Biomarker, Biomarkers, CPD, Cutaneous carcinogenesis experimentation, Cyclobutane-pyrimidine dimers (CPD), Cytotoxic DNA photoproduct lesions, EpiDerm-FT, EpiDermFT, Full Thickness, Immunohistochemical expression, Irradiation, Irritancy, PCNA, Proliferating cell nuclear antigen (PCNA), Reactivity of biomarkers, UVB