Biological Mechanisms Induced by Low and Ultra Low doses of Ionizing Radiation

这项研究提案是正在进行的一个项目的一部分，该项目调查细胞对低剂量电离辐射暴露的反应机制。众所周知，高剂量的电离辐射会产生活性氧和氧化应激，这可能是致命的、诱变的、致癌的和致畸的。然而，在低剂量辐射下，可以诱导一种进化保守的适应性反应，通过维持和激活细胞防御机制来保护细胞。我们使用了DNA损伤和修复、细胞凋亡、氧化损伤、抗氧化酶活性和线粒体酶活性的标记物来研究低剂量下的生物反应。我们的研究计划为核、医疗、监管和立法机构提供了重要信息。我们已经证明，在穿过单个细胞的几个光子轨迹范围内的低剂量电离辐射可以诱导适应性反应。我们的研究基于这样一个假设，即低剂量辐射产生的氧化应激与自然本底水平一样，通过高度保守的适应性反应机制促进和维持基因组的稳定性。这项发现奖续期申请的具体目标是通过消除几乎所有的背景辐射(宇宙和地面)，专注于超低剂量下诱导的细胞机制。这将通过有选择地去除各种背景辐射质量(宇宙射线、来自氡及其子体产品的阿尔法，以及地球外部伽马光子)来实现。利用我们实验室建立的现代生物学终点，我们将试图理解自然背景辐射对生命必不可少的概念。在没有自然本底辐射的情况下，细胞系统就会摇摇欲坠。我们建议利用萨德伯里中微子天文台实验室(SNOLAB)独特的超低水平辐射环境，该实验室位于地球表面下6200英尺(完全是一个2000级洁净室)，以测量没有宇宙辐射、没有氡气和没有外部伽马辐射的生物过程和细胞后果(或益处)。我们建议使用一个简单和先进的细胞模型系统来测量酵母(酿酒酵母)的生长、DNA修复能力和突变，以及人类杂交细胞的转化。我们将比较从低于本底到高于正常本底的各种受控辐射暴露(通过添加氡或外部伽马)下的生物反应，以更好地了解与低剂量辐射暴露有关的细胞反应机制。这项研究将有助于阐明可能推动生物系统进化和/或选择的一些过程。

This research proposal is part of an ongoing program investigating mechanisms of cellular responses to low doses of ionizing radiation exposure. It is well known that high doses of ionizing radiation produce reactive oxygen species and oxidative stress which can be lethal, mutagenic, carcinogenic, and teratogenic. However, at low doses radiation can induce an an evolutionary conserved adaptive response that can protect cells by maintaining and activating cellular defence mechanisms. We have used markers of DNA damage and repair, apoptosis, oxidative damage, antioxidant enzyme activity, and mitochondrial enzyme activity to study biological responses at low doses. Our research program has provided important information to the nuclear, medical, regulatory, and legislative communities. We have shown that low doses of ionizing radiation in the range of several photon tracks through a single cell can induce an adaptive response.  Our research is based on the hypothesis that oxidative stress produced by low doses of radiation, like natural background levels, promotes and maintains genomic stability through a highly conserved adaptive response mechanism. This Discovery grant renewal application has the specific aim to focus on cellular mechanisms induced at ultra-low doses by eliminating virtually all background radiation (cosmic and terrestrial). This will be achieved by selectively removing various background radiation qualities (cosmic rays, alpha from radon and its daughter products, and terrestrial external gamma photons). Using modern biological endpoints well established in our laboratory, we will seek to understand the notion that natural background radiation is essential for life. In the absence of natural background radiation cellular systems falter. We propose to utilize the unique ultra-low level radiation environment in the Sudbury Neutrino Observatory Laboratory (SNOLAB) which is 6200 feet below the earth's surface (and entirely a Class 2000 clean room) to measure biological processes and cellular consequences (or benefits) of no cosmic radiation, no radon gas, and no external gamma radiation. We propose using a simple and advanced cellular model system to measure growth, DNA repair capacity and mutation in yeast (Saccharomyces cerevisiae), and transformation in human hybrid cells. We will compare biological responses under various regimes of controlled radiation exposures (by adding radon, or external gamma) from below background to above normal background to better understand cellular response mechanisms to low dose radiation exposure. This research will help elucidate some of the processes that may drive evolution and/or selection in living systems.