Effects of ultraviolet B exposure on the expression of proliferating cell nuclear antigen in murine skin.

Proliferating cell nuclear antigen (PCNA) is an active nuclear protein involved in DNA replication, recombination and repair. PCNA is found throughout the basal layer in normal skin and in all layers of the epidermis in malignancy. This study evaluates PCNA's expression after acute and chronic UV-B irradiation. Skh-1 hairless mice exposed to 1.5 and 4.5 kJ/m2 of UV-B were sacrificed at 6, 12, 24, 48, 72 and 168 h. Immunohistochemical analysis revealed PCNA expression throughout the basal layer of untreated skin, with diminished expression at 6 h, indicative of immediate UV damage, and evidenced by the observable upregulation in pyrimidine dimer formation early on. Subsequently, PCNA immunoreactivity progressively increased, demonstrating an aberrant upward epidermal migratory pattern in association with chronic exposure. The 4.5 kJ/m2 group exhibited prolonged recovery in staining and also demonstrated this altered migratory pattern with chronic exposure. Progressive reactivation of PCNA expression occurs with repair. PCNA migration to upper layers of the epidermis indicates proliferation and possibly a subsequent increased malignant potential. We conclude that PCNA can serve as a marker of DNA repair and indirectly as an indicator of UV-B-induced damage, expression being time dependent and dose related. Specific immunoreactivity patterns and the observable atypia in keratinocytes are relevant in elucidating malignant potentiation.

Isoflavone genistein: photoprotection and clinical implications in dermatology.

Genistein is a soybean isoflavone with diverse biological activities. It is a potent antioxidant, a specific inhibitor of protein tyrosine kinase, and a phytoestrogen. In recent years, increasing evidence has accumulated that this natural ingredient shows preventative and therapeutic effects for breast and prostate cancers, postmenopausal syndrome, osteoporosis, and cardiovascular diseases in animals and humans. In the past decade we have conducted a series of studies and demonstrated that genistein has significant antiphotocarcinogenic and antiphotoaging effects. Genistein substantially inhibits skin carcinogenesis and cutaneous aging induced by ultraviolet (UV) light in mice, and photodamage in humans. The mechanisms of action involve protection of oxidative and photodynamically damaged DNA, downregulation of UVB-activated signal transduction cascades, and antioxidant activities. In this article, we review the biological activities of genistein, as well as published and unpublished research from our laboratory. In addition, we discuss the potential application of genistein to clinical dermatology.