Title:The Radiation Bystander Effect and its Potential Implications for Human Health
Volume: 12
Issue: 5
Author(s): M. Mancuso, E. Pasquali, P. Giardullo, S. Leonardi, M. Tanori, V. Di Majo, S. Pazzaglia and A. Saran
Affiliation:
Keywords:
Bystander, cancer risk, genetic damage, in vivo mouse model, ionizing radiation
Abstract: A long-held dogma in radiation biology has been that the biological effects of exposure to ionizing
radiation occur as a result of damage in directly irradiated cells and that no effect would occur in neighboring
unirradiated cells. This paradigm has been frequently challenged by reports of radiation effects in unirradiated
or ‘bystander’ cells receiving signals from directly irradiated cells, an issue that may have substantial impact on
radiation risk assessment and development of radiation-based therapies. Radiation-induced bystander effects
have been shown in single-cell systems in vitro for an array of cancer relevant endpoints, and may trigger
damage in more complex 3-D tissue systems. They may be mediated by soluble factors released by irradiated
cells into the extracellular environment and/or by the passage of mediator molecules through gap-junction
intercellular communication. To date, evidence that radiation-associated bystander or abscopal responses are
effectual in vivo has been limited, but new data suggest that they may significantly affect tumor development in
susceptible mouse models. Further understanding of how the signal/s is transmitted to unirradiated cells and
tissues and how it provokes long-range and significant responses is crucial. By summarizing the existing
evidence of radiation induced bystander-like effects in various systems with emphasis on in vivo findings, we
will discuss the potential mechanisms involved in these observations and how effects in bystander cells
contribute to uncertainties in assessing cancer risks associated with radiation exposure.
