D'Orazio John, Jarrett Stuart, Amaro-Ortiz Alexandra, Scott Timothy
Graduate Center for Toxicology and the Departments of Pediatrics, Biomedical and Molecular Pharmacology and Physiology, Markey Cancer Center, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA.
Int J Mol Sci. 2013 Jun 7;14(6):12222-48. doi: 10.3390/ijms140612222.
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.
紫外线辐射（UV）被归类为“完全致癌物”，因为它既是一种诱变剂，也是一种非特异性损伤剂，兼具肿瘤起始剂和肿瘤促进剂的特性。在环境中，紫外线是皮肤癌和许多其他受环境影响的皮肤疾病最重要的可改变风险因素。然而，紫外线也通过介导皮肤中维生素D和内啡肽的天然合成对人类健康有益，因此紫外线对人类健康具有复杂和混合的影响。尽管如此，过度暴露于紫外线会带来严重的健康风险，包括萎缩、色素变化、皱纹和恶性肿瘤。在流行病学和分子层面上，紫外线与三种最常见的皮肤癌，即基底细胞癌、鳞状细胞癌和恶性黑色素瘤相关，每年这三种癌症共同影响超过100万美国人。遗传因素也会影响紫外线介导的皮肤疾病风险。特别是黑皮质素1受体（MC1R）基因的多态性与皮肤白皙、紫外线敏感性以及癌症风险增加相关。我们有兴趣在详细了解紫外线暴露后发生的分子事件的基础上开发紫外线防护方法，特别关注表皮黑素化以及MC1R在基因组维持中的作用。
