Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and Cancer-Related Fatigue (CRF) are syndromes with considerable overlap with respect to symptoms. There have been many studies that have ...compared the two conditions, and some of this research suggests that the etiologies of the conditions are linked in some cases. In this narrative review, CFS/ME and cancer are introduced, along with their known and putative mechanistic connections to multiple stressors including ionizing radiation. Next, we summarize findings from the literature that suggest the involvement of HPA-axis dysfunction, the serotonergic system, cytokines and inflammation, metabolic insufficiency and mitochondrial dysfunction, and genetic changes in CRF and CFS/ME. We further suspect that the manifestation of fatigue in both diseases and its causes could indicate that CRF and CFS/ME lie on a continuum of potential biological effects which occur in response to stress. The response to this stress likely varies depending on predisposing factors such as genetic background. Finally, future research ideas are suggested with a focus on determining if common biomarkers exist in CFS/ME patients and those afflicted with CRF. Both CFS/ME and CRF are relatively heterogenous syndromes, however, it is our hope that this review assists in future research attempting to elucidate the commonalities between CRF and CFS/ME.
Purpose: This review, which arose from a Radiation Research Society History symposium, traces the history of 'bystander effects' or 'indirect effects'(also known as 'abscopal effects', 'clastogenic ...effects' and more recently 'the secretosome'). In 1905, Murphy first drew attention to effects caused by the injection of irradiated cells into animals. In the present day, bystander effects are seen as part of the secretosome, where they coordinate responses to stressors at the tissue, organism, and population level. The review considers the history and also the reasons why this process of information exchange/communication appears to have been discovered and forgotten several times. The review then considers the evolution of our understanding of the mechanisms and what relevance these effects may have in radiation protection and radiotherapy.
Conclusions: The authors conclude that the phenomenon currently described as a 'bystander effect' has been described under a variety of different names since 1905. However recent advances in biology have made it possible to investigate mechanisms and potential impacts more fully. This has led to the current upsurge in research into this effect of radiation.
The field of low dose radiobiology has advanced considerably in the last 30 years from small indications in the 1980's that all was not simple, to a paradigm shift which occurred during the 1990's, ...which severely dented the dose-driven models and DNA centric theories which had dominated until then. However while the science has evolved, the application of that science in environmental health protection has not. A reason for this appears to be the uncertainties regarding the shape of the low dose response curve, which lead regulators to adopt a precautionary approach to radiation protection. Radiation protection models assume a linear relationship between dose (i.e. energy deposition) and effect (in this case probability of an adverse DNA interaction leading to a mutation). This model does not consider non-targeted effects (NTE) such as bystander effects or delayed effects, which occur in progeny cells or offspring not directly receiving energy deposition from the dose. There is huge controversy concerning the role of NTE with some saying they reflect “biology” and that repair and homeostatic mechanisms sort out the apparent damage while others consider them to be a class of damage which increases the size of the target. One thing which has recently become apparent is that NTE may be very critical for modelling long-term effects at the level of the population rather than the individual. The issue is that NTE resulting from an acute high dose such as occurred after the A-bomb or Chernobyl occur in parallel with chronic effects induced by the continuing residual effects due to radiation dose decay. This means that if ambient radiation doses are measured for example 25 years after the Chernobyl accident, they only represent a portion of the dose effect because the contribution of NTE is not included.
•This paper presents a new concept in Environmental Radiobiology, which could explain why effects are detected in Chernobyl and Fukushima wildlife at ambient doses which are very low.•We suggest that non-targeted effects such as genomic instability, lethal mutations and bystander signalling, contribute a persistent legacy dimension to the total measured effect.•This “historic dose” component needs to be incorporated into dose effect models in order to predict true levels of risk.
Purpose: To investigate biochemical pathways known to be involved in radiation response and in CFIDS to determine if there might be common underlying mechanisms leading to symptoms experienced by ...those accidentally or deliberately exposed to radiation and those suffering from CFIDS. If such a link was established to suggest testable hypotheses to investigate the mechanisms with the aim of identifying new therapeutic targets.
Conclusions: Evidence for involvement of the alpha-synuclein, cytochrome c oxidase, αB-crystallin, RNase L, and lactate dehydrogenase/STAT1 pathways is strong and suggests a common underlying mechanism involving mitochondrial dysfunction mediated by ROS and disruption of ATP production. The downstream effect of this is compromised energy production. Testable hypotheses are suggested to investigate the involvement of these pathways further.
It is well established that cells, tissues, and organisms exposed to low doses of ionizing radiation can induce effects in non-irradiated neighbors (non-targeted effects or NTE), but the mechanisms ...remain unclear. This is especially true of the initial steps leading to the release of signaling molecules contained in exosomes. Voltage-gated ion channels, photon emissions, and calcium fluxes are all involved but the precise sequence of events is not yet known. We identified what may be a quantum entanglement type of effect and this prompted us to consider whether aspects of quantum biology such as tunneling and entanglement may underlie the initial events leading to NTE. We review the field where it may be relevant to ionizing radiation processes. These include NTE, low-dose hyper-radiosensitivity, hormesis, and the adaptive response. Finally, we present a possible quantum biological-based model for NTE.
Non-targeted effects (NTE) such as bystander effects or genomic instability have been known for many years but their significance for radiotherapy or medical diagnostic radiology are far from clear. ...Central to the issue are reported differences in the response of normal and tumour tissues to signals from directly irradiated cells. This review will discuss possible mechanisms and implications of these different responses and will then discuss possible new therapeutic avenues suggested by the analysis. Finally, the importance of NTE for diagnostic radiology and nuclear medicine which stems from the dominance of NTE in the low-dose region of the dose-response curve will be presented. Areas such as second cancer induction and microenvironment plasticity will be discussed.
The phenomenon by which irradiated organisms including cells in vitro communicate with unirradiated neighbors is well established in biology as the radiation-induced bystander effect (RIBE). ...Generally, the purpose of this communication is thought to be protective and adaptive, reflecting a highly conserved evolutionary mechanism enabling rapid adjustment to stressors in the environment. Stressors known to induce the effect were recently shown to include chemicals and even pathological agents. The mechanism is unknown but our group has evidence that physical signals such as biophotons acting on cellular photoreceptors may be implicated. This raises the question of whether quantum biological processes may occur as have been demonstrated in plant photosynthesis. To test this hypothesis, we decided to see whether any form of entanglement was operational in the system. Fish from 2 completely separate locations were allowed to meet for 2 hours either before or after which fish from 1 location only (group A fish) were irradiated. The results confirm RIBE signal production in both skin and gill of fish, meeting both before and after irradiation of group A fish. The proteomic analysis revealed that direct irradiation resulted in pro-tumorigenic proteomic responses in rainbow trout. However, communication from these irradiated fish, both before and after they had been exposed to a 0.5 Gy X-ray dose, resulted in largely beneficial proteomic responses in completely nonirradiated trout. The results suggest that some form of anticipation of a stressor may occur leading to a preconditioning effect or temporally displaced awareness after the fish become entangled.
The International Journal of Radiation Biology (IJRB) celebrates its 60th birthday this year. Ahead of this very special issue, we wanted to produce strong representations of the journal's ...publication history in order to celebrate the current status of the journal and to look forward to its future. This was accomplished using 'reference maps'. Reference data were used from 1959 onward from the highest-cited paper in IJRB, for each respective year, to create a figure displaying when those articles were cited in IJRB since their publication. This was done to show the relative impact of historical IJRB papers to future research. Common themes of research were also examined by decade. Additionally, to show the historical impact of the journal outside of its immediate area of research and its practical applications, information on IJRB articles cited by the International Commission on Radiological Protection (ICRP) was collected. It was in 1959 when IJRB published the first issue, and when ICRP also issued Publication 1. Among all Publications (1-139), 43 publications have thus far cited 320 IJRB papers and each of which have been cited 1-7 times. Most notably, Publications 90, 99, 118, and 131 cited more than 40 IJRB papers. Further research was done into references for IJRB's contemporary journal: Radiation Research. The most highly cited IJRB articles for each year together since its inception were cited 16,760 times since they were published and cited 1385 times in Radiation Research. Together, these three datasets and their representations show the diversity of historical IJRB publications, the impact of historical IJRB articles in both future research in the journal and outside of it, and articles which new prospective authors contributing to IJRB might find useful in their own research.
Towards a New Concept of Low Dose Mothersill, Carmel; Rusin, Andrej; Seymour, Colin
Health physics (1958),
09/2019, Letnik:
117, Številka:
3
Journal Article
Recenzirano
When people discuss the risks associated with low doses of ionizing radiation, central to the discussion is the definition of a low dose and the nature of harm. Standard answers such as "doses below ...0.1 Gy are low" or "cancer is the most sensitive measure of harm" obscure the complexity within these seemingly simple questions. This paper will discuss some of the complex issues involved in determining risks to human and nonhuman species from low-dose exposures. Central to this discussion will be the role of communicable responses to all stressors (often referred to as bystander responses), which include recently discovered epigenetic and nontargeted mechanisms. There is a growing consensus that low-dose exposure to radiation is but one of many stressors to impact populations. Many of these stressors trigger responses that are generic and not unique to radiation. The lack of a unique radiation signature makes absolute definition of radiation risk difficult. This paper examines a possible new way of defining low dose based on the systemic response to the radiation. Many factors will influence this systemic response and, because it is inherently variable, it is difficult to predict and so makes low-dose responses very uncertain. Rather than seeking to reduce uncertainty, it might be valuable to accept the variability in outcomes, which arise from the complexity and multifactorial nature of responses to stressors.
Chronic fatigue and Immune Dysfunction Syndrome (CFIDS) is a heterogeneous disease that may be promoted by various environmental stressors, including viral infection, toxin uptake, and ionizing ...radiation exposure. Previous studies have identified mitochondrial dysfunction in CFIDS patients, including modulation of mitochondrial respiratory chain activity, deletions in the mitochondrial genome, and upregulation of reactive oxygen species (ROS). This paper focuses on radiation effects and hypothesizes that CFIDS is primarily caused by stressor-induced mitochondrial metabolic insufficiency, which results in decreased energy production and anabolic metabolites required for normal cellular metabolism. Furthermore, tissues neighbouring or distant from directly perturbed tissues compensate for this dysfunction, which causes symptoms associated with CFIDS. This hypothesis is justified by reviewing the links between radiation exposure and CFIDS, cancer, immune dysfunction, and induction of oxidative stress. Moreover, the relevance of mitochondria in cellular responses to radiation and metabolism are discussed and putative mitochondrial biomarkers for CFIDS are introduced. Implications for diagnosis are then described, including a potential urine assay and PCR test for mitochondrial genome mutations. Finally, future research needs are offered with an emphasis on where rapid progress may be made to assist the afflicted.
PDF
