Radiation-induced bystander effects: are they good, bad or both?

Our current knowledge of the mechanisms underlying the induction of bystander effects by low dose-low linear-energy-transfer ionising radiation is reviewed, and the question of how bystander effects may be related to observed adaptive responses, systemic genomic instability or other effects of low doses exposures is considered. Bystander effects appear to be the result of a generalised stress response in tissues or cells. The signals may be produced by all exposed cells but the response may require a quoram in order to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response, which has many characteristics of apoptosis but may be detected in cell lines without p53 expression. While a death response might appear to be adverse, it can in fact be protective and remove damaged cells from the population. Since many cell populations carry damaged cells without being exposed to radiation ('background damage') low doses exposures might cause removal of cells damaged by agents other than the test dose of radiation, which would lead to the production of 'u- or n-shaped' dose-response curves. The level of harmful or beneficial response would then be related to the background damage carried by the cell population and the genetic programme determining response to damage. This model may be important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors.