New insights on radiation-induced bystander signalling and its relationship to DNA repair

Kevin M. Prise*, Susanne Burdak-Rothkamm, Melvyn Folkard, Genro Kashino, Chunlin Shao, Laurence Tartier

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Since the first observations of bystander responses in cells and tissues, a major emphasis of radiation biology research in recent years has been to determine the role of cell-cell signalling in the response of cells to irradiation. Bystander responses are observed when cells respond to their neighbours being irradiated and have been predicted to play an important role in the response to low dose exposure. A key question is what role DNA damage and repair plays in the bystander process and in cells where the nucleus has not been directly irradiated. In a range of studies we have started to elucidate the relevance of DNA damage and repair pathways in both irradiated and bystander cells. In several model systems, including normal and tumour cells we have consistently found that production of a bystander signal does not require direct irradiation of the nucleus of the targeted cell and the formation of direct DNA damage. Direct irradiation of the cytoplasm outside the nucleus does, however, trigger DNA damage dependent sensors. Cells release bystander signals independently of the dose or level of DNA damage potentially produced. Signals are also released whether the targeted cell survives the exposure or not. This strongly suggests that initial levels of DNA damage in targeted cells or the involvement of repair processes are not important in signal release. New evidence suggests that Ataxia-telagiectasia and Rad3 related (ATR)-dependent signalling may play an important role in the response of cells to non-DNA-targeted damage.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalInternational Congress Series
Volume1299
DOIs
Publication statusPublished - 01 Feb 2007
Externally publishedYes

Keywords

  • Bystander effect
  • Cell-signalling
  • Cytoplasmic target
  • DNA repair
  • Microbeam

ASJC Scopus subject areas

  • Medicine(all)

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