Radiation-induced bystander effects: Relevance for radiation protection of human and non-human biota

In this paper our current knowledge of the mechanisms underlying the induction of bystander effects by low dose low LET ionizing radiation is reviewed in the context of relevance to radiation protection issues. The question of how bystander effects may be related to observed adaptive responses, systemic genomic instability or other effects of low doses exposures is also considered. Bystander effects appear to be the result of a generalized stress response in tissues or cells. The signals may be produced by all exposed cells, but the response may require additional system parameters to exist in order to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response. This can manifest as apoptotic cell death, terminal differentiation, reproductive cell death or necrosis. While a death response might appear to be adverse, the position is argued in this paper, that it can in fact be protective and remove damaged cells from the reproducing population. Since many cell populations carry damaged cells without being exposed to radiation (so-called “background damage”), it is possible that low dose radiation exposures cause removal of cells damaged by agents other than the test dose of radiation. This mechanism would lead to the production of “u- or n-shaped” dose response curves. In this scenario, the level of harmful or beneficial response will be related to the background damage carried by the cell population and the genetic program determining response to damage. This model may be particularly important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors on biota.