Melanoma and ultraviolet light: from physiology to pathology

Epidemiologic data: The frequency of malignant melanoma, by far the most fa tal skin cancer, has increased by a factor of approximately 15 in the past 60 years. The factors underlying this rapid increase are incompletely under stood, although ultraviolet radiations are likely strongly implicated. Epid emiologic studies demonstrate the role of altered patterns of sun exposure, and overexposition to UVA radiation, as confirmed by experimental data on animal models. Biological aspects: Melanin produced by melanocytes has a photoprotective f unction in the skin, whereas UVB-induced DNA damage enhance the repair capa city of these cells. However, this photoprotective effect is not induced by intense intermittent sun exposure. In addition, melanocytes demonstrate re sistance to UVB-induced apoptosis and are thus at high risk for incorporati ng UV-induced mutations. Molecular aspects: Different mutations in suscepitbility genes (CDKN2A, INK 4), or in genes implicated in control of cell cycle or maintenance of cell integrity (DNA repair) are involved in initiation and promotion steps of me lanocarcinogenesis. Moreover, tumor progression is stimulated by UVB throug h the activation of different target genes that are implicated in control o f melanoma environment (immune surveillance, angiogenesis, growth factors.. .).