RISK EVALUATION IN THE LOW-DOSE RANGE CT FOR RADIATION-EXPOSED CHILDREN, BASED ON DNA DAMAGE

Abstract One of the most common usages of radiation in current medical diagnosis is computed tomography (CT) using X-rays. The potential health risk of CT scans has been discussed in various studies to determine whether low-dose radiation from CT could enhance the chromosome aberration yields in pediatric patients and increase their risk of carcinogenesis. For this reason, it is of great interest to study the effects of low-dose radiation. The induction of DNA damage by a CT scan examination has been demonstrated in several reports by the γ-H2AX assay, the micronuclei assay and dicentrics measurements. However, the results of most studies showed limitations. On the other hand, epidemiological studies give contradictory results for post-natal radiation exposure in the low-dose range, so it is still difficult to draw conclusions about the effects of CT examinations and risk of carcinogenesis. This article provides an overview of previously published data and summarizes the current state of knowledge.

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Radiation-induced versus endogenous DNA damage: possible effect of inducible protective responses in mitigating endogenous damage

Human & Experimental Toxicology ◽

10.1191/0960327103ht365oa ◽

2003 ◽

Vol 22 (6) ◽

pp. 290-306 ◽

Cited By ~ 111

Author(s):

Myron Pollycove ◽

Ludwig E Feinendegen

Keyword(s):

Dna Damage ◽

Low Dose ◽

Published Data ◽

Low Dose Radiation ◽

Dna Damages ◽

Cellular Protection ◽

Radiation Sources ◽

Radiation Induced Cancer ◽

Radiation Induced ◽

Dose Radiation

Ionizing radiation (IR) causes damage to DNA that is apparently proportional to absorbed dose. The incidence of radiation-induced cancer in humans unequivocally rises with the value of absorbed doses above about 300 mGy, in a seemingly linear fashion. Extrapolation of this linear correlation down to zero-dose constitutes the linear-no-threshold (LNT) hypothesis of radiation-induced cancer incidence. The corresponding dose-risk correlation, however, is questionable at doses lower than 300 mGy. Non-radiation induced DNA damage and, in consequence, oncogenic transformation in non-irradiated cells arises from a variety of sources, mainly from weak endogenous carcinogens such as reactive oxygen species (ROS) as well as from micronutrient deficiencies and environmental toxins. In order to relate the low probability of radiation-induced cancer to the relatively high incidence of non-radiation carcinogenesis, especially at low-dose irradiation, the quantitative and qualitative differences between the DNA damages from non-radiation and radiation sources need to be addressed and put into context of physiological mechanisms of cellular protection. This paper summarizes a co-operative approach by the authors to answer the questions on the quantitative and qualitative DNA damages from non-radiation sources, largely endogenous ROS, and following exposure to low doses of IR. The analysis relies on published data and justified assumptions and considers the physiological capacity of mammalian cells to protect themselves constantly by preventing and repairing DNA damage. Furthermore, damaged cells are susceptible to removal by apoptosis or the immune system. The results suggest that the various forms of non-radiation DNA damage in tissues far outweigh corresponding DNA damage from low-dose radiation exposure at the level of, and well above, background radiation. These data are examined within the context of low-dose radiation induction of cellular signaling that may stimulate cellular protection systems over hours to weeks against accumulation of DNA damage. The particular focus is the hypothesis that these enhanced and persisting protective responses reduce the steady state level of nonradiation DNA damage, thereby reducing deleterious outcomes such as cancer and aging. The emerging model urgently needs rigorous experimental testing, since it suggests, importantly, that the LNT hypothesis is invalid for complex adaptive systems such as mammalian organisms.

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Reactive oxygen species in cell responses to toxic agents

Human & Experimental Toxicology ◽

10.1191/0960327102ht216oa ◽

2002 ◽

Vol 21 (2) ◽

pp. 85-90 ◽

Cited By ~ 87

Author(s):

L E Feinendegen

Keyword(s):

Radiation Exposure ◽

Mammalian Cells ◽

Low Dose ◽

X Rays ◽

Low Dose Radiation ◽

Cell Responses ◽

Toxic Agents ◽

Particle Tracks ◽

Dose Radiation

This review first summarizes experimental data on biological effects of different concentrations of ROS in mammalian cells and on their potential role in modifying cell responses to toxic agents. It then attempts to link the role of steadily produced metabolic ROS at various concentrations in mammalian cells to that of environmentally derived ROS bursts from exposure to ionizing radiation. The ROS from both sources are known to both cause biological damage and change cellular signaling, depending on their concentration at a given time. At low concentrations signaling effects of ROS appear to protect cellular survival and dominate over damage, and the reverse occurs at high ROS concentrations. Background radiation generates suprabasal ROS bursts along charged particle tracks several times a year in each nanogram of tissue, i.e., average mass of a mammalian cell. For instance, a burst of about 200 ROS occurs within less than a microsecond from low-LET irradiation such as X-rays along the track of a Compton electron (about 6 keV, ranging about 1 μm). One such track per nanogram tissue gives about 1 mGy to this mass. The number of instantaneous ROS per burst along the track of a 4-meV ¬-particle in 1 ng tissue reaches some 70000. The sizes, types and sites of these bursts, and the time intervals between them directly in and around cells appear essential for understanding low-dose and low dose-rate effects on top of effects from endogenous ROS. At background and low-dose radiation exposure, a major role of ROS bursts along particle tracks focuses on ROS-induced apoptosis of damage-carrying cells, and also on prevention and removal of DNA damage from endogenous sources by way of temporarily protective, i.e., adaptive, cellular responses. A conclusion is to consider low-dose radiation exposure as a provider of physiological mechanisms for tissue homoeostasis.

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Low-Dose Radiation Activates Akt and Nrf2 in the Kidney of Diabetic Mice: A Potential Mechanism to Prevent Diabetic Nephropathy

Oxidative Medicine and Cellular Longevity ◽

10.1155/2012/291087 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 30

Author(s):

Xiao Xing ◽

Chi Zhang ◽

Minglong Shao ◽

Qingyue Tong ◽

Guirong Zhang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Low Dose ◽

X Rays ◽

Diabetic Mice ◽

Low Dose Radiation ◽

Single Exposure ◽

Akt Phosphorylation ◽

And Function ◽

Nrf2 Expression ◽

Dose Radiation

Repetitive exposure of diabetic mice to low-dose radiation (LDR) at 25 mGy could significantly attenuate diabetes-induced renal inflammation, oxidative damage, remodeling, and dysfunction, for which, however, the underlying mechanism remained unknown. The present study explored the effects of LDR on the expression and function of Akt and Nrf2 in the kidney of diabetic mice. C57BL/6J mice were used to induce type 1 diabetes with multiple low-dose streptozotocin. Diabetic and age-matched control mice were irradiated with whole body X-rays at either single 25 mGy and 75 mGy or accumulated 75 mGy (25 mGy daily for 3 days) and then sacrificed at 1–12 h for examining renal Akt phosphorylation and Nrf2 expression and function. We found that 75 mGy of X-rays can stimulate Akt signaling pathway and upregulate Nrf2 expression and function in diabetic kidneys; single exposure of 25 mGy did not, but three exposures to 25 mGy of X-rays could offer a similar effect as single exposure to 75 mGy on the stimulation of Akt phosphorylation and the upregulation of Nrf2 expression and transcription function. These results suggest that single 75 mGy or multiple 25 mGy of X-rays can stimulate Akt phosphorylation and upregulate Nrf2 expression and function, which may explain the prevention of LDR against the diabetic nephropathy mentioned above.

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First Insights into the Effect of Low-Dose X-Ray Irradiation in Adipose-Derived Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20236075 ◽

2019 ◽

Vol 20 (23) ◽

pp. 6075 ◽

Cited By ~ 2

Author(s):

Annemarie Schröder ◽

Stephan Kriesen ◽

Guido Hildebrandt ◽

Katrin Manda

Keyword(s):

Stem Cells ◽

Low Dose ◽

Dose Range ◽

Adipose Derived Stem Cells ◽

Long Term Effects ◽

Low Dose Radiation ◽

Term Survival ◽

Cell Therapies ◽

Dose Radiation

(1) Background: Emerging interest of physicians to use adipose-derived stem cells (ADSCs) for regenerative therapies and the fact that low-dose irradiation (LD-IR ≤ 0.1 Gy) has been reported to enhance the proliferation of several human normal and bone-marrow stem cells, but not that of tumor cells, lead to the idea of improving stem cell therapies via low-dose radiation. Therefore, the aim of this study was to investigate unwanted side effects, as well as proliferation-stimulating mechanisms of LD-IR on ADSCs. (2) Methods: To avoid donor specific effects, ADSCs isolated from mamma reductions of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival assay was used to classify the long-term effects of low-dose radiation in ADSCs. Afterwards, cytotoxicity and genotoxicity, as well as the effect of irradiation on proliferation of ADSCs were investigated. (3) Results: LD (≤ 0.1 Gy) of ionizing radiation promoted the proliferation and survival of ADSCs. Within this dose range neither geno- nor cytotoxic effects were detectable. In contrast, greater doses within the dose range of >0.1–2.0 Gy induced residual double-strand breaks and reduced the long-term survival, as well as the proliferation rate of ADSCs. (4) Conclusions: Our data suggest that ADSCs are resistant to LD-IR. Furthermore, LD-IR could be a possible mediator to improve approaches of stem cells in the field of regenerative medicine.

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The Role of the DNA Damage Response Mechanisms after Low-Dose Radiation Exposure and a Consideration of Potentially Sensitive Individuals

Radiation Research ◽

10.1667/rr1844.1 ◽

2010 ◽

Vol 174 (6b) ◽

pp. 825-832 ◽

Cited By ~ 24

Author(s):

Penny Jeggo

Keyword(s):

Dna Damage ◽

Radiation Exposure ◽

Dna Damage Response ◽

Low Dose ◽

Low Dose Radiation ◽

Damage Response ◽

Dose Radiation

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Radiophobia: 7 Reasons Why Radiography Used in Spine and Posture Rehabilitation Should Not Be Feared or Avoided

Dose-Response ◽

10.1177/1559325818781445 ◽

2018 ◽

Vol 16 (2) ◽

pp. 155932581878144 ◽

Cited By ~ 13

Author(s):

Paul A. Oakley ◽

Deed E. Harrison

Keyword(s):

Low Dose ◽

Background Radiation ◽

Threshold Model ◽

Radiation Risk ◽

Biomechanical Analysis ◽

Cellular Damage ◽

Imaging Method ◽

X Rays ◽

Low Dose Radiation ◽

Dose Radiation

Evidence-based contemporary spinal rehabilitation often requires radiography. Use of radiography (X-rays or computed tomography scans) should not be feared, avoided, or have their exposures lessened to decrease patient dose possibly jeopardizing image quality. This is because all fears of radiation exposures from medical diagnostic imaging are based on complete fabrication of health risks based on an outdated, invalid linear model that has simply been propagated for decades. We present 7 main arguments for continued use of radiography for routine use in spinal rehabilitation: (1) the linear no-threshold model for radiation risk estimates is invalid for low-dose exposures; (2) low-dose radiation enhances health via the body’s adaptive response mechanisms (ie, radiation hormesis); (3) an X-ray with low-dose radiation only induces 1 one-millionth the amount of cellular damage as compared to breathing air for a day; (4) radiography is below inescapable natural annual background radiation levels; (5) radiophobia stems from unwarranted fears and false beliefs; (6) radiography use leads to better patient outcomes; (7) the risk to benefit ratio is always beneficial for routine radiography. Radiography is a safe imaging method for routine use in patient assessment, screening, diagnosis, and biomechanical analysis and for monitoring treatment progress in daily clinical practice.

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