Genistein, the most abundant
isoflavone of the soy derived
phytoestrogen compounds, is a potent
antioxidant and inhibitor of
tyrosine kinase. We 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 we elucidate
genistein's photoprotective efficacy within the context of 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 microM) 1 h prior to UVB radiation at 20 and 60 mJ/cm2.
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/cm2, 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/cm2 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 our 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 human reconstituted skin. The implications of our findings serve as compelling validation to our conclusions that
genistein may serve as a potent chemopreventive agent against photocarcinogenesis.