PHOTOPROTECTIVE EFFECT OF ISOFLAVONE GENISTEIN ON ULTRAVIOLET B-INDUCED PYRIMIDINE DIMER FORMATION AND PCNA EXPRESSION IN HUMAN RECONSTITUTED SKIN AND ITS IMPLICATIONS IN DERMATOLOGY AND PREVENTION OF CUTANEOUS CARCINOGENESIS.

This study by researchers at Mount Sinai School of Medicine demonstrated that MatTek’s EpiDermFT epidermal/dermal human skin tissue equivalent can be used to investigate the photoprotective efficacy of compounds by exposing treated and untreated EpiDermFT tissues to UVB radiation. Genistein, the most abundant isoflavone of the soy derived phytoestrogen compounds, is a potent antioxidant and inhibitor of tyrosine kinase. Researchers at the Mount Sinai School of Medicine (USA) previously reported the antiphotocarcinogenic effects of genistein in SKH-1 murine skin, including its capacity for scavenging reactive oxygen species, inhibiting photodynamic DNA damage and downregulating UVB (ultra violet B)-induced signal transduction cascades in carcinogenesis. In this study, Mount Sinai School of Medicine researchers elucidate genistein’s photoprotective efficacy within the context of EpiDerm-FT, a full thickness human reconstituted skin, relative to acute challenges with ultraviolet-B irradiation. Skin samples were pre-treated with three concentrations of genistein (10, 20 and 50 mM) 1 h prior to UVB radiation at 20 and 60 mJ/cm^2. Proliferating cell nuclear antigen (PCNA) and pyrimidine dimer (PD) expression profiles were localized using immunohistochemical analysis on paraffin embedded samples 6 and 12 h post UVB exposure. Genistein dose dependently preserved cutaneous proliferation and repair mechanics at 20 and 60 mJ/cm^2, as evidenced by the preservation of proliferating cell populations with increasing genistein concentrations and noticeable paucity in PCNA immunoreactivity in the absence of genistein. Genistein inhibited UV-induced DNA damage, evaluated with PD immunohistochemical expression profiles, demonstrated an inverse relationship with increasing topical genistein concentrations. Irradiation at 20 and 60 mJ/cm^2 substantially induced PD formation in the absence of genistein, and a dose dependent inhibition of UVB-induced PD formation was observed relative to increasing genistein concentrations. Collectively all genistein pre-treated samples demonstrated appreciable histologic architectural preservation when compared with untreated specimens. These findings represent a critical link between the animal and cell culture studies with those of human skin and represent the first characterization of the dynamic alterations of UV-induced DNA damage and proliferating cell populations relative to pretreatment with genistein in (EpiDerm-FT) human reconstituted skin. The implications of these findings serve as compelling validation to the conclusion that genistein may serve as a potent chemopreventive agent against photocarcinogenesis.

Acanthosis, Antioxidant, Antiphotocarcinogenic, Carinogenesis, Chemopreventive agent, Cytoxicity, DNA damage, EFT-200, EpiDerm, EpiDerm-FT, EpiDermFT, Epidermal growth factor receptor (EGFR), Full thickness human reconstituted skin, Genistein (4’,5,7-trihydroxyisoflavone), Hydropic changes, Hyperplasia, Immunoreactivity, Isoflavone, Non-melanoma skin cancer (NMSC), Normal human keratinocytes (NHK), Paracrine signaling, Photocarcinogenesis, Photodynamic DNA damage, Photoprotective, Proliferating cell nuclear antigen (PCNA), Pyrimidine dimers (PD), Spongiosis, UV irradiation, Ultraviolet B (UVB), Vacuolization

EpiDerm-FT, Genistein, Isoflavone, Phystoestrogen