| Popis: |
Solar UV radiation is one of the most abundant carcinogens in our natural environment. Despite its strong genotoxicity and prevalent mutations in sun-exposed adult skin, skin cancers develop mostly late in life in a minority of fair-skinned Caucasians, attesting to the skin’s excellent adaptation. Although epidemiologic studies on skin cancer in the general population clearly incriminate sun exposure as an important etiologic factor, these studies provide little or no information on underlying mechanisms. The discovery that the dramatically increased skin cancer risk in Xeroderma pigmentosum patients is related to their defective repair of UV-induced DNA damage has greatly advanced our understanding of UV carcinogenesis. This rare syndrome revealed both the importance of DNA repair and the strong carcinogenic challenge from ambient UV radiation. Although molecular analyses of skin cancers have identified key somatic changes in various genes, it remains largely obscure as to whether and how, and to what extent UV radiation has caused these changes, with the notable exception of mutations in Notch and p53 genes from skin carcinomas which show a clear UV signature. |
