Physical transmission of bystander signals following ionising radiation exposure

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Radiation is a word that frightens people mainly because it is a known cancer-causing agent. Therefore it is regulated very strictly unless being used in medicine. There is considerable controversy concerning the real risks of low dose exposures and the relevant mechanisms which could determine those risks. Currently there is an assumption of a linear dose response relationship but that appears to be more a compromise to satisfy opposing factions rather than anything based on good science. With the possibility of increased dependence on nuclear power as a carbon neutral energy source, and increased use of radiation in medical diagnostic tests such as CT scans, there is an urgent need to gain a better understanding of the factors driving the dose response after low dose exposure. Our group have focused on this question for many years and have characterised non-targeted effects (NTE) such as the bystander effect and genomic instability. These are effects in cells, organs or organisms which did not get traversed by the radiation track but received signals from those that did. Our previous studies have shown that these NTE dominate the radiation dose response after low dose exposure, suggesting that the mechanisms operating in the low dose region are very different to the well known double strand DNA breaks which occur after high doses. This makes it imperative to understand what is going on after low dose exposure and whether the risk of low doses is greater or less than would be expected from high dose exposure. During the last NSERC Discovery grant period our laboratory discovered that the elusive primary bystander signal is physical not chemical as initially thought. UVA photons have been detected coming from irradiated cells and these have been shown to trigger a range of responses in cells and organisms which are associated both with “good” and “bad” outcomes. The current proposal seeks to understand the physical processes involved in the transduction of the initial ionising radiation energy to cause UV emission and how the UV is captured to initiate and transduce the characteristic bystander effects. The experiments will build on previous work and seek to characterise thespectrum of emissions from the biological material and the subsequentfate of emitted photons with the aim of understanding the biophysicalprocesses involved. Only when the basic physical mechanisms are understood will it be possible to better define the biological downstream consequences and propose protective strategies.