Protein Oxidation in Skin Cells by Tan Bed Irradiation

描述(由申请人提供)： 长期目标是确定UVA(290-320 nm)和UVB(320-400 nm)辐射的损伤、保护和恢复所涉及的特定细胞机制。暴露在太阳UVA/UVB辐射下的增加与皮肤癌的增加有关。由于(1)平流层臭氧层的侵蚀；(2)更多的户外娱乐活动时间；(3)晒黑床的使用增加，UVA/UVB增加了对人类健康的影响。在美国，平均每天有100多万人光顾日光浴沙龙，将自己暴露在比阳光高出10倍的UVA辐射中，具体取决于所使用的日光浴类型。在过去的三年里，晒黑床的使用率在14岁的女孩中从7%增加到15岁时的16%，到17岁时增加到35%。研究表明，晒黑床的使用增加与皮肤癌发病率的上升之间存在联系。2003年约有7500人死于黑色素瘤。高强度UVA日光浴床照射和太阳紫外线照射的结合显著增加了肿瘤的发生率，并削弱了细胞修复DNA损伤的能力。高活性氧自由基介导了UVA辐射的损伤效应。蛋白质是活性氧自由基的主要靶标之一。利用人类角质形成细胞和成纤维细胞，这项研究的一个具体目标将是量化在日光浴床下进行标准剂量照射后蛋白质氧化的程度与太阳照射强度(剂量水平)的关系。关键抗氧化酶活性水平的变化将与蛋白质氧化相关。已知的诱导氧化防御基因的硒将被用来确定其减少UVA诱导的蛋白质氧化修饰的潜力。研究方法将包括蛋白质凝胶电泳法和蛋白质印迹法，以识别和量化各种照射条件下的氧化蛋白质，以确定改变强度、剂量或暴露周期是否可以减少蛋白质氧化。这项研究具有重要意义，因为它将有助于制定战略，将增加使用日晒床的有害影响降至最低，尽管已公布了日光浴床对健康的危害警告；它将有助于制定医学上的光保护和光治疗策略。这项研究将对本科教学环境产生影响，为正在为健康相关专业的职业生涯做准备的学生提供多种研究机会，通过设计和进行实验、收集数据并解释它们对人类健康的意义来发展批判性思维技能。

DESCRIPTION (provided by applicant): The long-term objective is to identify the specific cellular mechanisms involved in the damage, protection and recovery from UVA (290-320 nm) and UVB (320-400 nm) irradiation. Increased exposure to solar UVA/UVB irradiation is related to the rise in skin cancer. Human health is affected by increased UVA/UVB due to (1) the erosion of the stratospheric ozone layer; (2) more time spent outdoors in recreational activities, and (3) increased use of tanning beds. On an average day in the United States, more than one million people visit a tanning salon and expose themselves to UVA radiation with intensity up to 10 times higher than sunlight depending on the type of tanning bed used. During the last 3 years, use of tanning beds increased from 7% among 14-year-old girls to 16% by age 15, and 35% by age 17. Studies show a connection between the increased use of tanning beds and a higher incidence of skin cancer. Approximately 7,500 deaths will be attributed to melanoma in 2003. The combination of high intensity UVA tanning bed irradiation and solar UV irradiation significantly increases tumor incidence and impairs the ability of cells to repair DNA damage. Highly reactive oxygen radicals mediate the damaging effects of UVA irradiation. Proteins are one of the major targets of reactive oxygen radicals. Using human keratinocytes and fibroblasts, a specific aim of this study will be to quantify the extent of protein oxidation after standard doses of irradiation delivered under tanning bed vs. solar irradiation intensity (fluence levels). Changes in activity levels of key antioxidant enzymes will be correlated with protein oxidation. Selenium, known to induce genes in oxidative defense, will be used to determine its potential for reducing UVA-induced oxidative modification of proteins. The research methods will include protein gel electrophoresis and western blots to identify and quantify oxidized proteins under a variety of irradiation conditions to determine if changes in intensity, dose or exposure cycles can decrease protein oxidation. This research is significant because it will help to develop strategies to minimize the harmful effects of increased use of tanning beds despite the published warnings of their health hazards; it will contribute to the development of photo-protective and photo-therapeutic strategies in medicine. This research will have an impact on the undergraduate teaching environment by providing multiple research opportunities for students, who are preparing for careers in the health-related professions, to develop critical thinking skills by designing and conducting experiments, collecting data and interpreting their significance to human health.