Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate–Dependent Manner

Dias, Juliana; Gloaguen, C.; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni

doi:10.1177/1559325818755238

Cited by 17 publications

(16 citation statements)

References 67 publications

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“…Nonetheless, decreased inflammatory cytokine production, reduced migration, and increased chemotaxis in macrophages ha ve also been observed [156]. A recent study by our group showed the importance of dose rate on endothelial cells ' molecular and functional responses; upregulation of antioxidant and anti -inflammatory gene expression after chronic low dose rate exposure (6 mGy/h) produced an adaptive response even when the dose reached 2 Gy [157].…”

Section: Immune/inflammatory Reactionsmentioning

confidence: 76%

Adaptive responses to low doses of radiation or chemicals: their cellular and molecular mechanisms

Guéguen

Bontemps

Ebrahimian

2018

Cell. Mol. Life Sci.

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This article reviews the current knowledge on the mechanisms of adaptive response to low doses of ionizing radiation or chemical exposure. A better knowledge of these mechanisms is needed to improve our understanding of health risks at low level s of environmental or occupational exposure and their involvement in cancer or non-cancer diseases. This response is orchestrated through a multifaceted cellular program involving the concerted action of diverse stress response pathways. These evolutionary highly conserved defense mechanisms determine the cellular response to chemical and physical aggression. They include DNA damage repair (p53, ATM, PARP pathways), antioxidant response (Nrf2 pathway), immune/inflammatory response (NK-B pathway), cell survival/death pathway (apoptosis), endoplasmic response to stress (UPR response), and other cytoprotective processes including autophagy, cell cycle regulation, and the unfolded protein response. The coordinated action of these processes induced by low-dose radiation or chemicals produces biological effects that are currently estimated with the linear non-threshold model. These effects are controversial. They are difficult to detect because of their low magnitude, the scarcity of events in humans, and the difficulty of corroborating associations over the long term. Improving our understanding of these biological consequences should help humans and their environment by enabling better risk estimates , the revision of radiation protection standards, and possible therapeutic advances .

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Section: Immune/inflammatory Reactionsmentioning

confidence: 76%

Adaptive responses to low doses of radiation or chemicals: their cellular and molecular mechanisms

Guéguen

Bontemps

Ebrahimian

2018

Cell. Mol. Life Sci.

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“…Since no DNA DSBs are observed, the changes in 8-oxo-dG and FRAP levels can also be explained by an adaptive response 4,[93][94][95] . Since 8-oxo-dG excretion and antioxidant capacity both increase in children, it could indicate that the intracellular defence mechanisms are being 'primed' , i.e.…”

Section: Discussionmentioning

confidence: 99%

Quantification of DNA Double Strand Breaks and Oxidation Response in Children and Adults Undergoing Dental CBCT Scan

Belmans

Gilles

Vermeesen

et al. 2020

Sci Rep

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Assessing the possible biological effects of exposure to low doses of ionizing radiation (IR) is one of the prime challenges in radiation protection, especially in medical imaging. Today, radiobiological data on cone beam CT (CBCT) related biological effects are scarce. In children and adults, the induction of DNA double strand breaks (DSBs) in buccal mucosa cells and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) and antioxidant capacity in saliva samples after CBCT examination were examined. No DNA DSBs induction was observed in children nor adults. In children only, an increase in 8-oxo-dG levels was observed 30 minutes after CBCT. At the same time an increase in antioxidant capacity was observed in children, whereas a decrease was observed in adults. Our data indicate that children and adults react differently to IR doses associated with CBCT. Fully understanding these differences could lead to an optimal use of CBCT in different age categories as well as improved radiation protection guidelines. Uncertainties concerning low dose ionizing radiation exposure and medical imaging. Currently, a debate exists within the radiation protection community about which model best reflects the relation between the ionizing radiation (IR) dose and the additional health risk. Several models have been described thus far. These include: the linear non-threshold (LNT) model, the linear threshold model, the hormetic model and the hypersensitivity model 1. Currently, the linear non-threshold (LNT) model is used to estimate risks in radiation protection guidelines. Although the LNT model is supported by epidemiological evidence in the high dose range (>100 milliGray (mGy)), increasing evidence disproves it in the low dose range 2-5. One of the main critiques is the fact that the LNT model does not take into account biological defence mechanisms (e.g. DNA repair mechanisms) 6,7. In addition, a lot of uncertainties still exist about low doses (<100 mGy), mostly because of a lack of statistical power of the epidemiological data. Knowing which of these models supports the relation between exposure to low doses of IR and the involved risk best is of importance in medical imaging applications of IR. Such applications include computed tomography (CT) and, more recently, cone beam computed tomography (CBCT), which typically uses doses far below 100 mGy, (typically between 0.01-0.10 mGy) 8-11. Multiple controversial studies indicate that exposure of children to diagnostic radiology may lead to radiation-induced malignancies later in life. Retrospective studies observed that the use of CT scans in children could triple the risk of leukaemia and brain cancers 12-14. A 24% increase in cancer incidence was seen in an

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“…As a second step, and despite the limitations described above, a small subset of 24 reports involving original human data mentioned in the title or in the abstract was identified. It represents 8.8% and 5.1% of all the inventoried papers, respectively 15 -38 (Tables 1 and 2). By analyzing these reports, 3 major conclusions can be drawn: – There are few original human data about hormesis.…”

Section: Radiation Hormesis In Humans: Few Data Available In Literaturementioning

confidence: 99%

Influence of Individual Radiosensitivity on the Hormesis Phenomenon: Toward a Mechanistic Explanation Based on the Nucleoshuttling of ATM Protein

et al. 2020

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Hormesis is a low-dose phenomenon that has been reported to occur, to different extents, in animals, plants, and microorganisms. However, a review of the literature shows that only a few reports describe it in humans. Also, the diversity of experimental protocols and cellular models used makes deciphering the mechanisms of hormesis difficult. In humans, hormesis mostly appears in the 20 to 75 mGy dose range and in nontransformed, radioresistant cells. In a previous paper by Devic et al, a biological interpretation of the adaptive response (AR) phenomenon was proposed using our model that is based on the radiation-induced nucleoshuttling of the ATM protein (the RIANS model). Here, we showed that the 20 to 75 mGy dose range corresponds to a maximum amount of ATM monomers diffusing into the nucleus, while no DNA double-strand breaks is produced by radiation. These ATM monomers are suggested to help in recognizing and repairing spontaneous DNA breaks accumulated in cells and contribute to reductions in genomic instability and aging. The RIANS model also permitted the biological interpretation of hypersensitivity to low doses (HRS)—another low-dose phenomenon. Hence, for the first time to our knowledge, hormesis, AR, and HRS can be explained using the same unified molecular model.

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Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate–Dependent Manner

Cited by 17 publications

References 67 publications

Adaptive responses to low doses of radiation or chemicals: their cellular and molecular mechanisms

Adaptive responses to low doses of radiation or chemicals: their cellular and molecular mechanisms

Quantification of DNA Double Strand Breaks and Oxidation Response in Children and Adults Undergoing Dental CBCT Scan

Influence of Individual Radiosensitivity on the Hormesis Phenomenon: Toward a Mechanistic Explanation Based on the Nucleoshuttling of ATM Protein

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