Nutrients, Oxidation and New Genetic Pathways for Cancer

癌症的营养素、氧化和新遗传途径

• 批准号: 6421766
• 负责人: Steven H Zeisel
• 金额: $ 9.95万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2002-07-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6421766
• 关键词: DNA damage; DNA repair; apoptosis; cell growth regulation; chemical carcinogen; chemical carcinogenesis; dietary constituent; free radical oxygen; mitogens; neoplasm /cancer genetics; nutrition aspect of cancer; nutrition related tag; oxidative stress; tissue /cell culture

This application responds to a request for proposals issued by the National Cancer Institute that asked for planning efforts that would result in an integrated research proposal to identify how nutrients modulate genetic and epigenetic pathways that are involved with cancer. We will develop an integrated plan to examine how nutrients modulate a series of related processes that mediate the genetic pathways involved in reactive oxygen mitogen production and DNA damage, mechanisms for repair of DNA, and the consequences of damage to DNA on genetic pathways that regulate cell cycling and elimination of damaged cells by apoptosis. This application is a logical extension of a group of already strong individual research programs that benefit from an integrated effort to enhance the cross-disciplinary character of the research. The cadre of investigators committed to this initial planning phase, along with many additional faculty members at UNC, is arguably one of the strongest groups in the world and bring innovative hypotheses and advanced methods to address the role of nutrition and genetic pathways in cancer pathophysiology. The basic premise of the current application is that nutrients interact in a specific manner to modulate various steps in the genetic and epigenetic pathways that mediate how oxidant stress causes cancer. Specifically: 1. Nutrients modulate how free radicals are generated and whether they survive to: (a) damage DNA; (b) activate signaling cascades involved in neoplastic transformation (mitogens, kinases, transcription factors, etc.), 2. Nutrients modify whether DNA is repaired or escapes repair, 3. Nutrients modify how DNA damage effects the genetic pathways and related signals that regulate cell cycling, 4. Nutrients modify how DNA damage effects the genetic pathways and related signals that regulate cell cycling, 5. Genetic polymorphisms exist which influence how nutrients interact with each of the above steps. The proposal will be enriched by continual interaction with experts and possible future collaborators from UNC-CH, the Research Triangle Park, as well as from other distinguished domestic and foreign academic and governmental institutions.

该申请响应国家癌症研究所发布的提案要求，要求进行计划工作，该计划将导致一项综合的研究建议，以确定营养如何调节与癌症有关的遗传和表观遗传途径。我们将制定一个综合计划，以研究营养如何调节一系列相关过程，这些过程介导了反应性氧促丝因产生和DNA损伤，DNA修复机制以及DNA对DNA损伤的后果以及调节细胞调节细胞的遗传途径的后果通过细胞凋亡循环和消除受损细胞。该应用程序是一组本已强大的个人研究计划的逻辑扩展，这些计划受益于增强研究的跨学科特征的综合努力。致力于这个初始计划阶段的研究人员以及UNC的许多其他教职员工可以说是世界上最强大的群体之一，并带来了创新的假设和高级方法来解决癌症病理生理学中营养和遗传途径的作用。当前应用的基本前提是，养分以特定方式相互作用，以调节遗传和表观遗传途径的各种步骤，这些步骤介导氧化剂应激如何引起癌症。具体：1。营养调节自由基的产生方式，以及它们是否生存至：（a）损伤DNA； （b）激活参与肿瘤转化的信号传导级联反应（有丝分裂剂，激酶，转录因子等），2。营养改变了DNA是修复还是逃避修复，3。营养改变了DNA损伤如何影响遗传途径和相关信号的调节信号，从而调节调节的信号细胞循环，4。养分改变了DNA损伤如何影响调节细胞循环的遗传途径和相关信号，5。存在遗传多态性，这些遗传多态性影响养分如何与上述每个步骤相互作用。该提案将通过与UNC-CH，研究三角公园以及其他杰出的国内外学术和政府机构的专家以及可能的未来合作者的持续互动来丰富该提案。