Abstract
UV radiation (UV) is classified as a “complete carcinogen” because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and molecularly linked to the three most common types of skin cancer, basal cell carcinoma, squamous cell carcinoma and malignant melanoma, which together affect more than a million Americans annually. Genetic factors also influence risk of UV-mediated skin disease. Polymorphisms of the melanocortin 1 receptor (MC1R) gene, in particular, correlate with fairness of skin, UV sensitivity, and enhanced cancer risk. We are interested in developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance.
Highlights
Markey Cancer Center, University of Kentucky College of Medicine, 800 Rose Street, Lexington, Graduate Center for Toxicology, University of Kentucky College of Medicine, 800 Rose Street, Tel.: +1-859-323-6238; Fax: +1-859-257-8940
While the importance of Nucleotide excision repair (NER) in Ultraviolet Radiation (UV) and skin cancer resistance is most clearly demonstrated by the natural history of patients with Xeroderma Pigmentosum (XP), attention is being paid to the role of NER polymorphisms on UV sensitivity and skin cancer incidence in sporadic populations
One of the greatest risk factors for the development of cutaneous melanoma is having a fair skin complexion, which is characterized by low levels of a UV-blocking dark pigment called eumelanin in the epidermis
Summary
Comprising roughly 16% of body mass, the skin is the largest organ of the body. Skin is organized into two primary layers, epidermis and dermis, which together are made up of epithelial, mesenchymal, glandular and neurovascular components. Keratinocytes are the most abundant cells in the epidermis and are characterized by their expression of cytokeratins and formation of desmosomes and tight junctions with each other to form an effective physicochemical barrier. The epidermis, demarcated from the dermis by a basement membrane, is organized into functional layers defined largely by keratinocyte characteristics such as size, shape, nucleation and keratin expression [7]. Besides the creation of a highly effective physical barrier, keratinocytes accumulate melanin pigments as they mature, and epidermal melanin functions to potently block UV penetration into the skin. Melanin synthesis is restricted to melanocytes, which are derived from neural crest and are the second most abundant cell in the epidermis [10,11]. Epidermal melanocytes are generally positioned in the basal layer above the basement membrane. The basic layers from the basement membrane outward are the stratum basale, stratum spinosum, stratum granulosum, and the stratum corneum, each identified by the morphology and differentiation state of the keratinocyte as indicated by expression of cytokeratins and other proteins
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