Bystander Signalling: Exploring Clinical Relevance Through New Approaches and New Models

Abstract

Classical radiation biology research has centred on nuclear DNA as the main target of radiation induced damage. Over the past two decades, this has been challenged by a significant amount of scientific evidence clearly demonstrating radiation induced cell signalling effects to have important roles in mediating overall radiobiological response. These effects, generally termed radiation induced bystander effects (RIBEs) have challenged the traditional DNA targeted theory in radiation biology Key wordsbystander effect, in vivo, ionising radiation, microbeam SearchesArticles cited in this manuscript were sourced through a literature search on the Medline/Pubmed database using the search terms 'radiation', bystander' 'in vivo' and 'microbeam'. Full articles were retrieved when the abstract was deemed relevant. The bibliographies of retrieved papers were also searched and relevant articles included.

Impacts of Terrestrial Ionizing Radiation on the Hematopoietic System

“…Radon-222 gas, even at lower doses, can enter the body through pulmonary alveoli; as a result, it can irradiate different organs, especially in the people who live near elevated levels of natural background radiation [49,50]. DNA damage and chromosomal aberrations were found in the peripheral blood lymphocytes and leukocytes of those workers who were exposed to uranium compounds emerging from lowdose radiation [51][52][53][54][55][56]. Also, mortalities from kidney, bladder, and esophagus cancers were likely to increase, but chronic renal diseases were observed to be significantly higher [57][58][59].…”

Time and Cell Type Dependency of Survival Responses in Co-cultured Tumor and Fibroblast Cells after Exposure to Modulated Radiation Fields

“…While RIBEs have classically been demonstrated at the cellular level in vitro using techniques including media transfer and co-culture, exposure to modulated radiation fields is a useful experimental approach to investigate RIBEs under conditions that more accurately represent clinical exposures (18). To date, investigations in this area have used single cell culture models, which fail to accurately represent cell-signaling effects between tumor and normal cells that may be occurring at margins or distinct compartments within the tumor microenvironment.…”

Clinical development of new drug–radiotherapy combinations

“…2). Radiation-induced bystander effects are bio logi cal effects caused in cells that have not been directly irradiated 20 . Such effects include DNA damage, chromo somal instability, mutation, and the induction of apoptosis 21 .…”