Responses to ionising radiation mediated by inflammatory mechanisms

Debayan Mukherjee (Lead / Corresponding author), Philip J. Coates, Sally A. Lorimore, Eric G. Wright

    Research output: Contribution to journalReview articlepeer-review

    77 Citations (Scopus)

    Abstract

    Since the early years of the twentieth century the biological consequences of exposure to ionising 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 inter-cellular signalling. Recently, it has become clear that all the various effects demonstrated in vivo may reflect an on-going 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 contribute also 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.
    Original languageEnglish
    Pages (from-to)289-299
    Number of pages11
    JournalJournal of Pathology
    Volume232
    Issue number3
    Early online date19 Nov 2013
    DOIs
    Publication statusPublished - Feb 2014

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