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

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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.