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）照射引起的损伤、保护和恢复所涉及的特定细胞机制。暴露于太阳UVA/UVB辐射的增加与皮肤癌的增加有关。人类健康受到UVA/UVB增加的影响，这是由于（1）平流层臭氧层的侵蚀;（2）在户外娱乐活动中花费更多的时间，以及（3）增加使用晒黑床。在美国，平均每天有超过100万人参观日光浴沙龙，并将自己暴露在UVA辐射下，其强度高达太阳光的10倍，具体取决于所使用的日光浴床的类型。在过去三年中，使用日光浴床的14岁女孩从7%增加到15岁的16%，17岁的35%。研究表明，越来越多地使用日光浴床与皮肤癌的发病率较高之间存在联系。2003年约有7 500人死于黑色素瘤。高强度UVA晒黑床照射和太阳紫外线照射的组合显着增加肿瘤发病率，并损害细胞修复DNA损伤的能力。高活性氧自由基介导UVA照射的损伤作用。蛋白质是活性氧自由基的主要目标之一。使用人角质形成细胞和成纤维细胞，本研究的一个具体目的将是量化标准剂量的照射后，在晒黑床与太阳辐射强度（通量水平）传递的蛋白质氧化的程度。关键抗氧化酶活性水平的变化将与蛋白质氧化相关。硒，已知诱导基因的氧化防御，将用于确定其减少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和蛋白质印迹，以识别和量化各种辐照条件下的氧化蛋白质，以确定强度，剂量或暴露周期的变化是否可以减少蛋白质氧化。这项研究意义重大，因为它将有助于制定策略，以最大限度地减少增加使用晒黑床的有害影响，尽管已发布有关其健康危害的警告;它将有助于医学中光保护和光治疗策略的发展。这项研究将对本科教学环境产生影响，为正在准备从事健康相关职业的学生提供多种研究机会，通过设计和进行实验，收集数据并解释其对人类健康的意义来培养批判性思维能力。

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.