Fundamental mechanisms & applications of low energy ion, electron, and photon interactions with biomolecular systems

基本机制

• 批准号: 299464-2013
• 负责人: Huels, Michael
• 金额: $ 1.97万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=526127
• 关键词: Fundamental; mechanisms; applications; low; energy

Although most of the energy deposited by ionizing radiation (energetic heavy ions, electrons or UV, X-ray, or gamma-rays) in living tissue is quickly channeled into production of abundant secondary ion fragments, radicals and electrons, traditional radiation science has largely ignored the early effects of many of these secondary particles, mainly ions and electrons. However, our previous work [Science 287, 1658 (2000)] has shown for the first time that even at unprecedented low energies their reactions lead to lethal breaks in DNA and the destruction of nucleic acid bases, whose sequence provides the actual genetic text inside the DNA; moreover, this leads to further production of numerous types of very reactive secondary ions. What is still not known is this: by what mechanisms do such ions initiate subsequent damage in DNA, or other important biomolecules. Our research will focus on the detailed reactions by which such ions can damage or modify DNA, using our novel technologies of microanalysis recently developed from methods of ion and electron beam physical chemistry, synchrotron accelerator technology, and biochemical radiation sciences. Moreover, our research will uncover the fundamental differences of how and by what mechanisms molecular damage is induced by the different types of radiation (ions, electrons and UV or X-rays). This multidisciplinary approach will complete our knowledge of the molecular origins of radiation damage, particularly by ions, and how this may promote cell death and mutations; such knowledge is essential for realistic radiation risk assessments for airline crews and astronauts (exposed to ionic space radiation), or reactor workers, and in cancer radiotherapy. The results of our studies will also provide knowledge to help us in the future to devise crucial new methods to control, or reduce, the side effects of radiation exposure, for example by designing new chemicals that protect DNA from such radiation, or sensitize cancer cells to therapeutic radiation, leading to lower dose to healthy tissue, thus less side effects.

虽然电离辐射（高能重离子、电子或紫外线、X射线或伽马射线）在活组织中沉积的大部分能量很快被引导到大量二次离子碎片、自由基和电子的产生中，但传统的辐射科学在很大程度上忽略了许多这些二次粒子（主要是离子和电子）的早期影响。然而，我们以前的工作[Science 287，1658（2000）]首次表明，即使在前所未有的低能量下，它们的反应也会导致DNA的致命断裂和核酸碱基的破坏，而核酸碱基的序列提供了DNA内部的实际遗传文本;此外，这还导致进一步产生许多类型的非常活跃的二次离子。目前尚不清楚的是：这些离子通过什么机制引发DNA或其他重要生物分子的后续损伤。我们的研究将集中在这些离子可以破坏或修改DNA的详细反应，使用我们最近从离子和电子束物理化学，同步加速器技术和生物化学辐射科学的方法开发的微量分析新技术。此外，我们的研究将揭示不同类型的辐射（离子，电子和紫外线或X射线）如何以及通过何种机制引起分子损伤的根本差异。这种多学科方法将使我们对辐射损伤的分子起源，特别是离子，以及这如何促进细胞死亡和突变的知识更加完整;这种知识对于航空公司机组人员和宇航员（暴露于离子空间辐射）或反应堆工作人员以及癌症放射治疗的现实辐射风险评估至关重要。我们的研究结果还将提供知识，帮助我们在未来设计关键的新方法来控制或减少辐射暴露的副作用，例如通过设计新的化学物质来保护DNA免受这种辐射，或使癌细胞对治疗辐射敏感，从而降低健康组织的剂量，从而减少副作用。