Epidemiology of protein glutathiolation

候选人的长期目标是发展研究专长和计划， 香烟烟雾引起的氧化应激对癌症的影响。一个多学科的教育和指导计划， 提出了这包括分子流行病学、遗传学和相关领域的教学课程， 参加研讨会、专业会议和其他主题培训机会 氧化应激或分子流行病学。导师制将包括实践培训和研究 在谷胱甘肽和癌症预防权威约翰·里奇博士和菲利普·拉扎勒斯博士的指导下， 宾夕法尼亚州立大学癌症中心副主任。几乎没有可靠的流行病学标志物， 氧化应激到目前为止，血液抗氧化剂维生素水平和氧化DMA或脂质 损伤已被用于研究癌症中的氧化应激。然而，这种标记提供的信息很少 关于细胞氧化还原状态的变化和致癌作用中关键蛋白质的改变。的 谷胱甘肽氧化为蛋白结合谷胱甘肽（GSSP）被认为是 氧化应激我们的初步研究表明，吸烟者的GSSP大幅增加。 中心假设是，香烟烟雾自由基引起氧化应激，通过血液测量 蛋白谷胱甘肽化，GSSP水平被氧化应激基因的多态性改变， 抗氧化剂和生活方式因素。 具体目标是： 1.确定血液中GSSP水平的种族差异，以响应阿利特诱导的氧化应激。 饮酒、饮食、MnSOD和HOGG 1基因多态性对血液的影响 GSSP水平。 2.确定肺癌和口腔癌的风险与血液中GSSP浓度的病例对照研究 问题研究对于肺癌，确定与MnSOD多态性相关的风险及其与 GSSP。 3.进行MAC补充对血液和口腔脱落细胞的随机干预试验 GSSP浓度。GSSP水平与氧化损伤标志物（包括8-OhdG、F-2）相关 异前列腺素、羰基蛋白和血浆维生素抗氧化剂水平。确定MAC的影响 补充后调整年龄，遗传多态性和其他因素。

The long-term goal of the candidate is to develop a research expertise and program in the contribution of cigarette smoke-induced oxidative stress to cancer. A multidisciplinary educational and mentoring program is proposed. This includes didactic courses in molecular epidemiology, genetics and related fields, and participation in workshops, professional conferences, and other training opportunities with a subject content in oxidative stress or molecular epidemiology. Mentorship will include hands-on training and research guidance under Dr. John Richie, an authority on glutathione and cancer prevention, and Dr. Philip Lazarus, Associate Director of the Penn State Cancer Center. There are few reliable epidemiologic markers of oxidative stress. To date proxy markers such as blood antioxidant vitamin levels and oxidative DMAor lipid damage has been used to study oxidative stress in cancer. However, such markers provide little information about changes in the redox status of cells and alterations in critical proteins involved in carcinogenesis. The oxidation of glutathione to protein-bound glutathiolation (GSSP) is proposed as a sensitive markerof oxidative stress. Our preliminary studies demonstrate substantial increases in GSSP in cigarette smokers. The central hypothesis is that cigarette smoke free radicals cause oxidative stress as measured by blood protein glutathiolation, and that GSSP levels are modified by polymorphisms in oxidative stress genes, antioxidants and lifestyle factors. The specific aims are: 1. Determine racial differences in blood GSSP levels in response to cigarette-induced oxidative stress. Measure the effects of alcohol consumption, diet, MnSOD and HOGG1 genetic polymorphisms on blood GSSP levels. 2. Determine the risk of lung and oral cancer associated with blood GSSP concentrations in case-control studies. For lung cancer, deternine the risk associated with the MnSOD polymorphism and its joint effect with GSSP. 3. Conduct a randomized intervention trial of MACsupplementation on blood and exfoliated buccal cell GSSP concentrations. Correlate levels of GSSP with markers of oxidative damage including 8-OhdG, F-2 isoprostanes, protein carbonyls, and plasma vitamin antioxidant levels. Determine the effects of MAC supplementation after adjustment for age, genetic polymorphisms and other factors.