Modeling of Molecular Mechanisms of Radiation Adaptive Response Formation
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The phenomenon of adaptive response is expressed in the increase of resistance of a biological object to high doses of mutagens under the conditions of previous exposure to these (or other) mutagens in low doses. Low doses of mutagen activate a number of protective mechanisms in a living object, which are called hormetic. Thus, the adaptive response and hormesis are links in the same chain. Radiation hormesis refers to the generally positive effect of low doses of low LET radiation on biological objects. The phenomenology of radiation-induced adaptive response and radiation hormesis for biological objects of different levels of organization is considered; the review of existing theories describing the dose-effect relationship has been reviewed. The hypothesis proposing one of the mechanisms of formation of radiation adaptive response of cells taking into account the conformational structure of chromatin has been submitted. The analysis of modern concepts of the phenomenon of hormesis on the basis of modeling of molecular mechanisms of formation of hormetic reactions to low-dose low LET radiation has been carried out. The parameters that can be used for quantitative and graphical evaluation of the phenomenon of hormesis was considered, and a formula for calculating the coefficient of radiation-induced adaptive response has been proposed. A review of mathematical models describing the radiation relative risk of gene mutations and neoplastic transformations at low-dose irradiation of cohorts has been performed. The following conclusions have been made: radiation hormesis and adaptive response are generally recognized as real and reproducible biological phenomena, which should be considered as very important phenomena of evolutionarily formed biological protection of living organisms from ionizing radiation. The hormesis model of dose-response relationship makes much more accurate predictions of a living object's response to radiation (or other stressors) in the low-dose range than the linear threshold (LNT) model does. The LNT model can adequately describe reactions only in the region of high doses of radiation, and, therefore, extrapolation modeling of biological object’s reactions from the zone of high doses to low doses is not correct.Keywords:
Hormesis
Adaptive response
Radiobiology
Modern medicine cannot exist without diagnostic and therapeutic methods that are based on ionizing radiation. Therefore it is necessary to understand interactions between this form of energy and living matter to make a full use of progress in radiobiology. Ionizing radiation is widely used for a relatively long time, that is how it is known, that disproportionately huge doses of ionizing radiation are particularly harmful for living organisms including humans. However low doses of radiation are useless in modern medicine. Broadening knowledge of radiobiology can be crucial for healthcare professionals.
Radiobiology
Non-ionizing radiation
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Hormesis
Adaptive response
Cellular stress response
Broad spectrum
Stimulus (psychology)
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The phenomenon of adaptive response is expressed in the increase of resistance of a biological object to high doses of mutagens under the conditions of previous exposure to these (or other) mutagens in low doses. Low doses of mutagen activate a number of protective mechanisms in a living object, which are called hormetic. Thus, the adaptive response and hormesis are links in the same chain. Radiation hormesis refers to the generally positive effect of low doses of low LET radiation on biological objects. The phenomenology of radiation-induced adaptive response and radiation hormesis for biological objects of different levels of organization is considered; the review of existing theories describing the dose-effect relationship has been reviewed. The hypothesis proposing one of the mechanisms of formation of radiation adaptive response of cells taking into account the conformational structure of chromatin has been submitted. The analysis of modern concepts of the phenomenon of hormesis on the basis of modeling of molecular mechanisms of formation of hormetic reactions to low-dose low LET radiation has been carried out. The parameters that can be used for quantitative and graphical evaluation of the phenomenon of hormesis was considered, and a formula for calculating the coefficient of radiation-induced adaptive response has been proposed. A review of mathematical models describing the radiation relative risk of gene mutations and neoplastic transformations at low-dose irradiation of cohorts has been performed. The following conclusions have been made: radiation hormesis and adaptive response are generally recognized as real and reproducible biological phenomena, which should be considered as very important phenomena of evolutionarily formed biological protection of living organisms from ionizing radiation. The hormesis model of dose-response relationship makes much more accurate predictions of a living object's response to radiation (or other stressors) in the low-dose range than the linear threshold (LNT) model does. The LNT model can adequately describe reactions only in the region of high doses of radiation, and, therefore, extrapolation modeling of biological object’s reactions from the zone of high doses to low doses is not correct.
Hormesis
Adaptive response
Radiobiology
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Hormetic dose response occurs for many endpoints associated with exposures of biological organisms to environmental stressors. Cell-based U- or inverted U-shaped responses may derive from common processes involved in activation of adaptive responses required to protect cells from stressful environments. These adaptive pathways extend the region of cellular homeostasis and are protective against ultimate cell, organ, and system toxicity. However, the activation of stress responses carries a significant energetic cost to the cell, leading to alterations of a variety of basal cellular functions in adapted or stressed cells. This tradeoff of resources between the unstressed and adapted states may lead to U-or inverted U-shaped dose response curves for some precursor endpoints. We examine this general hypothesis with chlorine, a prototype oxidative stressor, using a combination of cellular studies with gene expression analysis of response pathways and with computational modeling of activation of control networks. Discrete cellular states are expected as a function of exposure concentration and duration. These cellular states include normal functioning state, adaptive and stressed states at mild to intermediate exposures, and overt toxicity in the presence of an overwhelming concentration of stressors. These transitions can be used to refine default risk assessment practices that do not currently accommodate adaptive responses.
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Adaptive response
Stressor
Homeostasis
Cellular model
Cellular stress response
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The assay for trp5 gene conversion and ilv1-92 reversion in Saccharomyces cerevisiae strain D7 was used to characterize the induction of an adaptive response by hydrogen peroxide (H(2)O(2)). Effects of a small priming dose on the genotoxic effects of a larger challenge dose were measured in exponential cultures and in early stationary phase. An adaptive response, indicated by smaller convertant and revertant frequencies after the priming dose, occurred at lower priming and challenge doses in young, well-aerated cultures. Closely spaced priming doses from 0.000975 to 2 mM, followed by a 1 mM challenge, showed that the induction of the adaptive response is biphasic. In exponential cultures it was maximal with a priming dose of 0.125-0.25 mM. Very small priming doses were insufficient to induce the adaptive response, whereas higher doses contributed to damage. A significant adaptive response was detected when the challenge dose was administered 10-20 min after the priming exposure. It was fully expressed within 45 min, and the yeast began to return to the nonadapted state after 4-6 hr. Because of the similarity of the biphasic induction to hormetic curves and the proposal that adaptive responses are a manifestation of hormesis, we evaluated whether the low doses of H(2)O(2) that induce the adaptive response show a clear hormetic response without a subsequent challenge dose. Hormesis was not evident, but there was an apparent threshold for genotoxicity at or slightly below 0.125 mM. The results are discussed with respect to linear, threshold, and hormesis dose-response models.
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Adaptive response
Priming (agriculture)
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Hormesis
Dose rate
Low Dose Radiation
Dose dependence
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Hormesis
Adaptive response
Biomedicine
Discipline
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This section provides an overview of ionizing radiation exposure and radiation protection using computed tomography (CT). Patients undergoing CT examinations as part of their diagnosis or treatment are exposed to ionizing radiation. A net benefit is justified for patients against potential risks induced by exposure to ionizing radiation. This section contains two main subsections: (1) radiobiology and radiation protection and (2) radiation dose in CT examinations. The first subsection reviews the interactions between ionizing radiation and matter, biological effects of ionizing radiation, causative relationship between radiation exposures and their effects, and radiation protection methods. The second subsection systematically reviews radiation measurements with a special focus on CT dose metrics and discusses their applications and limitations.
Radiobiology
Non-ionizing radiation
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Hormesis
Radiobiology
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Through various researches and investigations it has been established that high doses of ionizing radiation are harmful to health. There is substantial controversy regarding the effects of low doses of ionizing radiation despite the large amount of work carried out (both laboratory and epidemiological). According to the linear no-threshold (LNT) hypothesis, any amount, however small, of radiation is potentially harmful, even down to zero levels. The threshold hypothesis, on the other hand, emphasizes that below a certain threshold level of radiation exposure, any deleterious effects are absent. At the same time, there are strong arguments, both experimental and epidemiological, which support the radiation hormesis (beneficial effects of low-level ionizing radiation). These effects cannot be anticipated by extrapolating from harmful effects noted at high doses. The choice of the approximate dose-response model for use in estimating the health effects of small doses of ionizing radiation remains controversial. In the present work, a comprehensive study of the available literature, data and reports of various radiation exposure and protection studies is presented. In conclusion, we find that the radiation hormesis contradicts the predictions made by the LNT hypothesis regarding the health effects of ionizing radiation in the low dose region.
Hormesis
Radiobiology
Background radiation
Low Dose Radiation
Threshold dose
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