Dose-Response: An International Journal: Volume 4, Issue 4
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2006-31-12
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Preface
(2006-12-01)
WILL RADIATION-INDUCED BYSTANDER EFFECTS OR ADAPTIVE RESPONSES IMPACT ON THE SHAPE OF THE DOSE RESPONSE RELATIONSHIPS AT LOW DOSES OF IONIZING RADIATION?
(2006-12-01) Morgan, William F
Radiation induced bystander effects and adaptive responses are two phenomena that modulate cellular responses to low doses of ionizing radiation. Bystander effects generally exaggerate the effects of low doses of radiation by eliciting detrimental effects in nonirradiated cells, thus making the target for radiation effects greater than the volume irradiated. Adaptive responses on the other hand indicate that low doses of radiation can reduce damage induced by a second challenging dose. The potential impact of these two low dose effects on the shape of the dose response relationship will be discussed.
RADIATION-INDUCED BYSTANDER AND ADAPTIVE RESPONSES IN CELL AND TISSUE MODELS
(2006-12-01) Prise, Kevin M; Folkard, Melvyn; Michael, Barry D
The use of microbeam approaches has been a major advance in probing the relevance of bystander and adaptive responses in cell and tissue models. Our own studies at the Gray Cancer Institute have used both a charged particle microbeam, producing protons and helium ions and a soft X-ray microprobe, delivering focused carbon-K, aluminium-K and titanium-K soft X-rays. Using these techniques we have been able to build up a comprehensive picture of the underlying differences between bystander responses and direct effects in cell and tissue-like models. What is now clear is that bystander dose-response relationships, the underlying mechanisms of action and the targets involved are not the same as those observed for direct irradiation of DNA in the nucleus. Our recent studies have shown bystander responses even when radiation is deposited away from the nucleus in cytoplasmic targets. Also the interaction between bystander and adaptive responses may be a complex one related to dose, number of cells targeted and time interval.
DEVELOPMENT OF AN IN VIVO ASSAY FOR DETECTION OF NONTARGETED RADIATION EFFECTS
(2006-12-01) Seymour, Colin; Mothersill, Carmel
An adaptive response may be defined as the effect of a small priming dose of radiation modifying the anticipated cellular response of the same tissues so as to alter the predicted response to a larger dose of radiation. We and others have demonstrated that at low radiation doses (less than 0.5 Gy) the lethal and mutational effect of the radiation is mainly, possibly entirely, due to the non-targeted effects. This is the dose range for priming doses in adaptive response protocols. In an associated presentation from our group, we demonstrate that the adaptive response may be explicable as a non targeted (bystander) response. In this paper we present data from exposed human patients, showing that a simple assay using blood can demonstrate variation in the extent and type of non-targeted effects and that exposure to radiation can modulate the subsequent non-targeted response to a later dose. Patients undergoing radiotherapy treatment for cancer gave blood samples immediately after the first dose, midway during and six weeks after therapy. The serum from these samples was harvested, diluted in tissue culture medium and added to reporter cells. The toxicity or growth promoting activity of the serum was measured using a clonogenic assay coupled with immunocytochemical measurement of various proteins involved in apoptosis or growth. There is already evidence that bystander effects are controlled by both genetic and epigenetic (lifestyle) factors. These data could support the development of a simple blood based assay to predict overall response of human subjects to low doses of radiation taking all the low dose factors into account.
RADIATION-INDUCED BYSTANDER EFFECTS: EVIDENCE FOR AN ADAPTIVE RESPONSE TO LOW DOSE EXPOSURES?
(2006-12-01) Mothersill, Carmel; Seymour, Colin
This paper reviews our current knowledge of the mechanisms underlying the induction of bystander effects by low dose, low-LET ionizing radiation and discusses how they may be related to observed adaptive responses or other protective effects of low dose exposures. 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 appears to require a quorum in order to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but is p53 independent. While a death response might appear to be adverse, the position is argued in this paper that it is in fact protective and removes damaged cells from the population. Since many cell populations carry damaged cells without being exposed to radiation, so called “background damage”, it is possible that low doses exposures cause removal of cells damaged by agents other than the test dose of radiation. This mechanism would lead to the production of “U-shaped” dose response curves. In this scenario, the level of “adaptive” or beneficial response will be related to the background damage carried by the cell population. This model may be important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors.