title: Non-targeted effects of radiation exposure: recent advances and implications.
abstract: The target theory of radiation-induced effects has been challenged by numerous studies, which indicate that in addition to biological effects resulting from direct DNA damage within the cell, a variety of non-DNA targeted effects (NTE) may make important contributions to the overall outcome. Ionising radiation induces complex, global cellular responses, such as genomic instability (GI) in both irradiated and never-irradiated 'bystander' cells that receive molecular signals produced by irradiated cells. GI is a well-known feature of many cancers, increasing the probability of cells to acquire the 'hallmarks of cancer' during the development of tumours. Although epidemiological data include contributions of both direct and NTE, they lack (i) statistical power at low dose where differences in dose response for NTE and direct effects are likely to be more important and (ii) heterogeneity of non-targeted responses due to genetic variability between individuals. In this article, NTE focussing on GI and bystander effects were critically examined, the specific principles of NTE were discussed and the potential influence on human health risk assessment from low-dose radiation was considered.
authors.affiliation: Genomic Instability Group, Department of Biological and Medical Sciences, Oxford Brookes University, Gipsy Lane, Oxford OX3 0BP, UK mkadhim@brookes.ac.uk.
authors.forename: M A
authors.initials: MA
authors.lastname: Kadhim
authors.affiliation: CRUK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, ORCRB Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Hill
mesh_terms: D024201:Bystander Effect / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects*; D042822:Genomic Instability / Q000528:radiation effects*; D006801:Humans; D000069079:Radiation Exposure / Q000009:adverse effects*; D011836:Radiation Tolerance; D011839:Radiation, Ionizing