Mechanisms underlying the effects of low doses of ionising radiation

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Objective: To investigate the signalosome of irradiated cells. Approach: Cell lines and live fish which give a robust non-targeted radiation response will be used to investigate the nature of the signal produced by irradiated cells and tissues and to determine how this signal is processed by cells and organisms which are not irradiated but receive signals from irradiated cells. Recent discoveries by our group strongly suggest there is a physical component to the signal which passes from irradiated to non-irradiated cells and organisms. We will test the hypothesis that low energy photons are involved using theoretical and experimental approaches. Significance and Novelty: Ever since the acceptance that non-targeted effects (NTE) can be measured in unirradiated cells or distant progeny of irradiated cells, the discussion has developed about the relevance of these effects for radiobiology and radiation protection since they increase the complexity of the radiation response and allow for outcomes which are not as predictable as they were under the "old rules". It is important to consider relevance for practical applications such as radiation protection and radiotherapy but also of interest is how they might influence ideas about evolution and adaptation of organisms. Important examples from our group are (i) the data showing that bystander mechanisms are either on or off in cells and that the "on" threshold appears to be at a very low dose (mGy range), (ii) data suggesting that adaptive responses are induced not only in neighbouring cells but in organisms which receive bystander signals and (iii) data showing that chronic exposures to alpha or gamma irradiation lead to complex responses in organisms which can be adaptive and protective. It is likely that consideration of these signalling mechanisms could also be of benefit in cancer biology providing new insights into the regulation of cancer cell social groups and how these interact with the host. This proposal seeks to clarify the nature of the signal and to determine how these effects may lead to adaptive changes at various levels of organisation.