Fundamental mechanisms and applications of soft landed ion reactions with biomolecular surfaces

生物分子表面软着陆离子反应的基本机制和应用

• 批准号: 299464-2007
• 负责人: Huels, Michael
• 金额: $ 2.73万
• 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: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=480847
• 关键词: Fundamental; mechanisms; applications; soft; landed

Although most of the energy deposited by ionizing radiation in living tissue is quickly channeled into production of abundant low energy ions and electrons, traditional radiation science has largely ignored the effects of many of these ultra-fast reacting particles. However, our recent work has shown for the first time that even at unprecedented low energies their reactions lead to lethal breaks in DNA, as well as disintegration or elimination 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 ions. What is still not known is this: how exactly 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, and various biomaterials, using our novel technologies of microanalysis recently developed from methods of atomic/molecular physics, biochemistry, and radiation sciences. This multifaceted approach will complete our knowledge of the early origins of radiation damage, and how this may promote cell death and mutations; such knowledge is essential for realistic dose (or risk) assessment in various radiation environments, e.g. for reactor workers, air crews on high altitude flights, astronauts, and in clinical radiotherapy. For the latter case, the knowledge obtained from our studies will allow us to develop new methods to control and target the effects of radiation down to the nanoscopic molecular level, for example by designing new chemicals that sensitize the DNA in cancer cells to ionizing radiation, potentially leading to lower doses in cancer radiotherapy. Finally, these ion reaction studies will also provide new knowledge required for the further development of biotechnologies, such as new labeling methods of molecules for biomedical imaging, the modification of tissue-friendly biomaterials for implants, or the synthesis of new materials surfaces for biosensors and biochips used to advance biomedical research and drug discovery.

尽管电离辐射在活体组织中沉积的大部分能量很快被引导到大量低能离子和电子的产生中，但传统的辐射科学在很大程度上忽视了许多这样的超快反应粒子的影响。然而，我们最近的工作首次表明，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，以及核酸碱基的解体或消除，这些碱基的序列提供了DNA中的实际遗传文本；此外，这还导致了许多类型的非常活跃的离子的进一步产生。目前尚不清楚的是：这些离子究竟是如何引发DNA或其他重要生物分子的后续损伤的。我们的研究将集中在这些离子可以破坏或修饰DNA和各种生物材料的详细反应上，使用我们最近从原子/分子物理、生物化学和辐射科学的方法发展起来的新的微量分析技术。这种多方面的方法将使我们对辐射损伤的早期起源以及这如何促进细胞死亡和突变的知识更加全面；这些知识对于在各种辐射环境中进行现实的剂量(或风险)评估是必不可少的，例如，对于反应堆工作人员、高空飞行的空勤人员、宇航员和临床放射治疗。对于后一种情况，从我们的研究中获得的知识将使我们能够开发新的方法来控制和瞄准辐射的影响，直到纳米分子水平，例如通过设计新的化学物质，使癌细胞中的DNA对电离辐射敏感，潜在地导致癌症放射治疗中的较低剂量。最后，这些离子反应研究还将提供生物技术进一步发展所需的新知识，如用于生物医学成像的分子的新标记方法，用于植入物的组织友好生物材料的改性，或用于促进生物医学研究和药物发现的生物传感器和生物芯片的新材料表面的合成。