title: Responses to ionizing radiation mediated by inflammatory mechanisms.
abstract: Since the early years of the twentieth century, the biological consequences of exposure to ionizing radiation have been attributed solely to mutational DNA damage or cell death induced in irradiated cells at the time of exposure. However, numerous observations have been at variance with this dogma. In the 1950s, attention was drawn to abscopal effects in areas of the body not directly irradiated. In the 1960s reports began appearing that plasma factors induced by irradiation could affect unirradiated cells, and since 1990 a growing literature has documented an increased rate of DNA damage in the progeny of irradiated cells many cell generations after the initial exposure (radiation-induced genomic instability) and responses in non-irradiated cells neighbouring irradiated cells (radiation-induced bystander effects). All these studies have in common the induction of effects not in directly irradiated cells but in unirradiated cells as a consequence of intercellular signalling. Recently, it has become clear that all the various effects demonstrated in vivo may reflect an ongoing inflammatory response to the initial radiation-induced injury that, in a genotype-dependent manner, has the potential to contribute primary and/or ongoing damage displaced in time and/or space from the initial insult. Importantly, there is direct evidence that non-steroidal anti-inflammatory drug treatment reduces such damage in vivo. These new findings highlight the importance of tissue responses and indicate additional mechanisms of radiation action, including the likelihood that radiation effects are not restricted to the initiation stage of neoplastic diseases, but may also contribute to tumour promotion and progression. The various developments in understanding the responses to radiation exposures have implications not only for radiation pathology but also for therapeutic interventions.
authors.affiliation: Centre for Oncology and Molecular Medicine, University of Dundee Medical School, Dundee, DD1 9SY, UK.
authors.forename: Debayan
authors.initials: D
authors.lastname: Mukherjee
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Coates
authors.forename: Sally A
authors.initials: SA
authors.lastname: Lorimore
authors.forename: Eric G
authors.initials: EG
authors.lastname: Wright
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000502:physiology / Q000528:radiation effects; D042822:Genomic Instability / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D011832:Radiation Injuries; D011839:Radiation, Ionizing
keywords: inflammation; macrophages; non-targeted effects; radiation; tissue microenvironment