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

这项研究提案是一个正在进行的计划的一部分，调查细胞对低剂量电离辐射暴露的反应机制。众所周知，高剂量电离辐射会产生活性氧和氧化应激，这些物质可能是致命的、致突变的、致癌的和致畸的。 然而，在低剂量下，辐射可以诱导进化保守的适应性反应，可以通过维持和激活细胞防御机制来保护细胞。 我们已经使用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，监管和立法界提供了重要信息。 我们已经表明，低剂量的电离辐射的范围内的几个光子轨道通过一个单一的细胞可以诱导适应性反应。 我们的研究是基于这样的假设，即低剂量辐射产生的氧化应激，像自然背景水平，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。 这一发现补助金更新申请的具体目标是通过消除几乎所有的背景辐射（宇宙和地球），重点关注超低剂量诱导的细胞机制。 这将通过有选择地消除各种背景辐射质量（宇宙射线、氡及其子体的α辐射和地球外部伽马光子）来实现。 利用我们实验室中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至关重要的概念。在没有自然背景辐射的情况下，细胞系统会动摇。我们建议利用萨德伯里中微子天文台实验室（SNOLAB）的独特的超低水平辐射环境，该实验室位于地球表面以下6200英尺（完全是2000级洁净室），以测量没有宇宙辐射，没有氡气，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而先进的细胞模型系统来测量生长，DNA修复能力和酵母（酿酒酵母）的突变，并在人类杂交细胞的转化。 我们将比较各种制度下的控制辐射暴露（通过添加氡，或外部伽马）从低于本底以上正常背景的生物反应，以更好地了解细胞的反应机制，低剂量辐射暴露。 这项研究将有助于阐明一些可能驱动生命系统进化和/或选择的过程。

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.