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This paper starts with a brief history of the birth of the field of radioecology during the Cold War with a focus on US activity. We review the establishment of the international system for radiation protection and the science underlying the guidelines. We then discuss the famous ICRP 60 statement that if "Man" is protected, so is everything else and show how this led to a focus in radioecology on pathways to "Man" rather than concern about impacts on environments or ecosystems. We then review the contributions of Radiation Research Society members and papers published in Radiation Research which contributed to the knowledge base about effects on non-human species. These fed into international databases and computer-based tools such as ERICA and ResRad Biota to guide regulators. We then examine the origins of the concern that ICRP 60 is not sufficient to protect ecosystems and discuss the establishment of ICRP Committee 5 and its recommendations to establish reference animals and plants. The review finishes with current concerns that reference animals and plants (RAPs) are not sufficient to protect ecosystems, given the complexity of interacting factors such as the climate emergency and discusses the efforts of ICRP, the International Union of Radioecologists and other bodies to capture the concepts of ecosystem services and ecosystem complexity modelling in radioecology., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

The aim of this paper is to review the history surrounding the discovery of lethal mutations, later described as delayed reproductive death. Lethal mutations were suggested very early on, to be due to a generalised instability in a cell population and are considered now to be one of the first demonstrations of "radiation-induced genomic instability" which led later to the establishment of the field of "non-targeted effects." The phenomenon was first described by Seymour et al. in 1986 and was confirmed by Trott's group in Europe and by Little and colleagues in the United States before being extended by Mendonca et al. in 1989, who showed conclusively that the distinguishing feature of lethal mutation occurrence was that it happened suddenly after about 9-10 population doublings in progeny which had survived the original dose of ionizing radiation. However, many authors then suggested that in fact, lethal mutations were implicit in the original experiments by Puck and Marcus in 1956 and were described in the extensive work by Sinclair in 1964, who followed clonal progeny for up to a year after irradiation and described "small colony formation" as a persistent consequence of ionizing radiation exposure. In this paper, we examine the history from 1956 to the present using the period from 1986-1989 as an anchor point to reach into the past and to go forward through the evolution of the field of low dose radiobiology where non-targeted effects predominate., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Abstract: It is now well accepted that the mechanisms induced by low-dose exposures to ionizing radiation (LDR) are different from those occurring after high-dose exposures. However, the downstream effects of these mechanisms are unclear as are the quantitative relationships between exposure, effect, harm, and risk. In this paper, we will discuss the mechanisms known to be important with an overall emphasis on how so-called "non-targeted effects" (NTE) communicate and coordinate responses to LDR. Targeted deposition of ionizing radiation energy in cells causing DNA damage is still regarded as the dominant trigger leading to all downstream events whether targeted or non-targeted. We regard this as an over-simplification dating back to formal target theory. It ignores that last 100 y of biological research into stress responses and signaling mechanisms in organisms exposed to toxic substances, including ionizing radiation. We will provide evidence for situations where energy deposition in cellular targets alone cannot be plausible as a mechanism for LDR effects. An example is where the energy deposition takes place in an organism not receiving the radiation dose. We will also discuss how effects after LDR depend more on dose rate and radiation quality rather than actual dose, which appears rather irrelevant. Finally, we will use recent evidence from studies of cataract and melanoma induction to suggest that after LDR, post-translational effects, such as protein misfolding or defects in energy metabolism or mitochondrial function, may dominate the etiology and progression of the disease. A focus on such novel pathways may open the way to successful prophylaxis and development of new biomarkers for better risk assessment after low dose exposures., (Copyright © 2024 Health Physics Society.)

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.

Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) is considered to be a multidimensional illness whose etiology is unknown. However, reports from Chernobyl, as well as those from the United States, have revealed an association between radiation exposure and the development of CFIDS. As such, we present an expanded model using a systems biology approach to explain the etiology of CFIDS as it relates to this cohort of patients. This paper proposes an integrated model with ionizing radiation as a suggested trigger for CFIDS mediated through UVA induction and biophoton generation inside the body resulting from radiation-induced bystander effects (RIBE). Evidence in support of this approach has been organized into a systems view linking CFIDS illness markers with the initiating events, in this case, low-dose radiation exposure. This results in the formation of reactive oxygen species (ROS) as well as important immunologic and other downstream effects. Furthermore, the model implicates melanoma and subsequent hematopoietic dysregulation in this underlying process. Through the identification of this association with melanoma, clinical medicine, including dermatology, hematology, and oncology, can now begin to apply its expansive knowledge base to provide new treatment options for an illness that has had few effective treatments.

Purpose: Radiation-induced bystander effect (RIBE), a non-targeted effect of ionizing radiation in which non-irradiated individuals behave as if they have been irradiated after interactions with irradiated individuals, has been well documented in vertebrates. However, little research has been done investigating RIBE in terrestrial insects, this paucity of invertebrate RIBE leads to lack of knowledge on invertebrates living in fallout and exclusion zones. This paper aims to better understand the impacts of RIBE on terrestrial insects. Methods and materials : House crickets who have interacted with irradiated crickets were examined to investigate population effects of ionizing radiation exposure to better understand RIBE in insects., Results: The results demonstrated RIBE in crickets and found that cohabitated males had higher growth rate (mg/day) when compared to non-cohabitated males. Further, cohabitated males and females matured significantly faster with no significant difference in maturation weight than non-cohabitated populations. Experiment with adult irradiated crickets found saturability of bystander signals and similar shifts in maturation parameters. These results highlight that bystander signals can impacted development and maturation in crickets., Conclusion: Given long-term impacts of RIBE in insects, these results may have significant implications for interactions between insects inhabiting fringe nuclear exclusion zones and those outside of it.

Purpose: We characterize for the first time the emission of acoustic waves from cultured cells irradiated with X-ray photon radiation., Methods and Materials: Human cancer cell lines (MCF-7, HL-60) and control cell-free media were exposed to 1 Gy X-ray photons while recording the sound generated before, during and after irradiation using custom large-bandwidth ultrasound transducer. The effects of dose rate and cell viability were investigated., Results: We report the first recorded acoustic signals captured from a collective pressure wave response to ionizing irradiation in cell culture. The acoustic signal was co-terminous with the radiation pulse, its magnitude was dependent on radiation dose rate, and live and dead cells showed qualitatively and quantitatively different acoustic signal characteristics. The signature of the collective acoustic peaks was temporally wider and with higher acoustic power for irradiated HL-60 than for irradiated MCF-7., Conclusions: We show that X-ray irradiation induces two cultured cancer cell types to emit a characteristic acoustic signal for the duration of the radiation pulse. The rapid decay of the signal excludes acoustic emissions themselves from contributing to the inter-organism bystander signal previously reported in intact animals, but they remain a potential component of the bystander process in tissues and cell cultures. This preliminary study suggests that further work on the potential role of radiation-induced acoustic emission (RIAE) in the inter-cellular bystander effect is merited.

The role of signalling in initiating and perpetuating effects triggered by deposition of ionising radiation energy in parts of a system is very clear. Less clear are the very early steps involved in converting energy to chemical and biological effects in non-targeted parts of the system. The paper aims to present a new model, which could aid our understanding of the role of low dose effects in determining ultimate disease outcomes. We propose a key role for electromagnetic signals resulting from physico-chemical processes such as excitation decay, and acoustic waves. These lead to the initiation of damage response pathways such as elevation of reactive oxygen species and membrane associated changes in key ion channels. Critically, these signalling pathways allow coordination of responses across system levels. For example, depending on how these perturbations are transduced, adverse or beneficial outcomes may predominate. We suggest that by appreciating the importance of signalling and communication between multiple levels of organisation, a unified theory could emerge. This would allow the development of models incorporating time, space and system level to position data in appropriate areas of a multidimensional domain. We propose the use of the term "infosome" to capture the nature of radiation-induced communication systems which include physical as well as chemical signals. We have named our model "the variable response model" or "VRM" which allows for multiple outcomes following exposure to low doses or to signals from low dose irradiated cells, tissues or organisms. We suggest that the use of both dose and infosome in radiation protection might open up new conceptual avenues that could allow intrinsic uncertainty to be embraced within a holistic protection framework.

Objective: To determine whether the width of the shoulder and the size of the bystander effect are correlated using clonal lineages derived from a cultured cell line., Methods: HCT 116 (p53 wildtype) cells were grown at cloning density and individual viable colonies were picked off and grown to establish a series of cell lines from both unirradiated and irradiated progenitors. These cell lines were then irradiated to generate full survival curves. Highly variant clones were then tested to determine the level of the bystander effect using a medium transfer protocol., Results: The multi-target model gave the best fit in these experiments and size of the shoulder n is assessed in terms of radiosensitivity. The parent cell line has an n value of 1.1 while the most variant clones have n values of 0.88 (Clone G) and 5.5 (Clone A). Clonal lines subject to irradiation prior to isolation differed in bystander signal strength in comparison to clonal lines which were not initially irradiated ( P = .055)., Conclusions: Based on these experiments we suggest there may be a link between shoulder size of a mammalian cell line and the strength of a bystander effect produced in vitro. This may have implications for radiotherapy related to out-of-field effects., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

This paper reviews the current understanding of low dose radiobiology, and how it has evolved from classical target theory. It highlights the uncertainty around low dose effects, which is due in part to the complexity of "context" surrounding the ultimate expression of biological effects following low dose exposure. The paper makes special reference to low dose non-targeted effects which, are currently ignored in radiation protection and population level risk assessment, because it is unclear what they mean for risk. The view of the authors is that this "lack of clarity" about what the effects mean is precisely the point. It indicates the uncertainty of outcomes after a given exposure. The uncertainty stems from multiple outcome options resulting from the intrinsic uncertainty of the stochastic interaction of low dose radiation with matter. This uncertainty should be embraced rather than eschewed. The impacts of the uncertainties identified in this paper is explored and an approach to quantifying mutation probability in relation to dose is presented., (Copyright © 2022. Published by Elsevier B.V.)

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: To study the environmental radiation effects of wild animals after the Fukushima Dai-ichi nuclear power plant accident, we assessed effects on hematopoietic progenitor cells (HPCs) in large Japanese field mice ( Apodemus speciosus )., Materials and Methods: A. speciosus were collected from three contaminated sites and control area. The air dose-rates at the control and contaminated areas were 0.96 ± 0.05 μGy/d (Hirosaki), 14.4 ± 2.4 μGy/d (Tanashio), 208.8 ± 31.2 μGy/d (Ide), 470.4 ± 93.6 μGy/d (Omaru), respectively. We investigated possible DNA damage and pro-inflammatory markers in the bone marrow (BM) cells. The colony-forming potential of BM cells was estimated by the number of HPC colony-forming cells. Radiation-induced genomic instability (RIGI) in HPCs was also analyzed by quantifying delayed DNA damage in CFU-GM clones., Results: Although no significant differences in DNA damage and inflammation markers in BM cells from control and contaminated areas, the number of HPC colonies exhibited an inverse correlation with air dose-rate. With regard to RIGI, no significant differences in DNA damage of CFU-GM clones between the mice from the control and the three contaminated areas., Conclusions: Our study suggests that low dose-rate radiation of more than 200 Gy/d reduced HPCs, possibly eliminating genomically unstable HPCs.

Objective: To describe the contributions of Marie Sklodowska-Curie and her daughter Irene Curie to radiation science and how these studies in physics, chemistry and medicine led to the need to study radiobiological effects., Conclusions: The seminal discoveries of Maria Sklodowska-Curie in radiation physics and chemistry provided the basis for later investigations of the effects of ionizing radiation on cells and tissues and the role of radioactivity in mutagenesis and carcinogenesis. Both Maria and Irene contributed to the development of radiotherapy and the use of x-rays and radioisotopes in medical diagnosis. Their legacy is not confined to their own generation but can be traced through grand- and great-grand-students of these pioneering women.

Objectives: This commentary reviews and evaluates the role of sound signals as part of the infosome of cells and organisms. Emission and receipt of sound has recently been identified as a potentially important universal signaling mechanism invoked when organisms are stressed. Recent evidence from plants, animals and microbes suggests that it could be a stimulus for specific or general molecular cellular stress responses in different contexts, and for triggering population level responses. This paper reviews the current status of the field with particular reference to the potential role of sound signaling as an immediate/early bystander effector (RIBE) during radiation-induced stress., Conclusions: While the chemical effectors involved in intercellular and inter-organismal signaling have been the subject of intense study in the field of Chemical Ecology, less appears to be known about physical signals in general and sound signals in particular. From this review we conclude that these signals are ubiquitous in each kingdom and behave very like physical bystander signals leading to regulation of metabolic pathways and gene expression patterns involved in adaptation, synchronization of population responses, and repair or defence against damage. We propose the hypothesis that acoustic energy released on interaction of biota with electromagnetic radiation may represent a signal released by irradiated cells leading to, or complementing, or interacting with, other responses, such as endosome release, responsible for signal relay within the unirradiated individuals in the targeted population.

Purpose: This review discusses recent developments in our understanding of biological and physiological mechanisms underlying radiation cataractogenesis. The areas discussed include effects of low-dose exposures to the lens including potential relevance of non-targeted effects, the development of new personal-protective equipment (PPE) and standards in clinical and nuclear settings motivated by the updated ICRP recommendations to mitigate exposures to the lens of the eye. The review also looks at evidence from the field linking cataracts in birds and mammals to low dose exposures., Conclusions: The review suggests that there is evidence that cataractogenesis is not a tissue reaction (deterministic effect) but rather is a low dose effect which shows a saturable dose response relationship similar to that seen for non-targeted effects in general. The review concludes that new research is needed to determine the dose response relationship in environmental studies where field data are contradictory and lab studies confined to rodent models for human exposure studies.

Purpose: This review focuses on recent research in understanding the different aspects of what society should expect from a radiological attack. Although some scenarios of a radiologic event can be impossible to be prepared for, the effort put toward educating and better preparing for these types of events can help minimize some of the issues. The different areas discussed in this review include radioisotopes of concern, detection of radiation dose, biological effects of ionizing radiation exposures, low dose effects, targeted and non-targeted effects (NTE), psychological effects, mitigations, with a brief mention of other considerations such as medical preparedness, communication, policy implications and ethical issues. This review also discusses solutions to rectify the issues faced at hand that may come up in the event of a radiologic terrorist attack., Conclusions: A review of recent work in the area shows that a multi-layered and interdisciplinary approach is needed to prepare for a radiological terrorist attack. As well as medical preparedness, the approach needs to include sociological and psychological planning as well as an understanding of ethical issues. Since the likely 'dirty bomb' scenarios may involve low dose exposures to high numbers of people, a much better theoretical and practical understanding of low dose radiobiology and the development of robust low dose exposure biomarkers is needed as part of an integrated plan.

Objectives: To describe the contribution of women radiobiologists in Ireland to the development of the discipline internationally and at home and to discuss the history of radiobiology in Ireland to date. This parallels the history of the evolution of a small radiobiology group in Kevin Street, Dublin Institute of Technology (DIT) which was formerly part of the City of Dublin Vocational Education Committee. There followed years of development first as a radiobiological research center which evolved in the FOCAS Research Institute now embedded within Technological University Dublin (TU Dublin)., Conclusions: Over the last 45 years, the women of the Radiation and Environmental Science Centre (RESC) contributed to the major paradigm shift in low dose radiobiology contributing exciting new research concerning non-targeted effects, including discovery of lethal mutations, medium transfer bystander mechanisms, and signaling pathways. They also developed translational research using human explant culture systems with unique immunocytochemical methods and more recently evolved to molecular and spectroscopic analysis of clinical samples. The RESC also developed unique in vitro research methods into effects of radiation on non-human species of concern in ecosystems.

Purpose: This investigation forms part of a wider study into the legacy effects of exposure of rainbow trout eggs 38 h after fertilization, eyed eggs, yolk sac larvae (YSL) or first feeders to a single 0.5 Gy X-ray dose, including the induction of a bystander effect, by the irradiated fish, to non-irradiated fish. Fish may be exposed to multiple environmental stressors, including waterborne metals, during their lifespan and, while there are data on how the legacy of early life stage irradiation and bystander effect induction is affected by waterborne aluminum and cadmium, there are no studies into the effects radiation or the radiation induced bystander effect on metal uptake. Therefore the aim of this investigation was to determine if the legacy of early life stage irradiation included an effect on copper uptake by adult fish and by non-irradiated bystander adult trout which swam with the irradiated fish., Methods: The four early life stages mentioned above were exposed to a single 0.5 Gy X-ray dose and then maintained, for two years with no further irradiation. At two years old the irradiated fish were allowed to swim, for 2 h with non-irradiated bystander trout (also two years old). After this time copper uptake was determined using 64 Cu., Results: Copper uptake was increased in adult trout irradiated as eggs at 48 h after fertilization and as first feeders but eyed egg or YSL irradiation had no effect. Copper uptake was also increased in the bystander trout which swam with trout irradiated as eggs at 48 h after fertilization and as eyed eggs but there was no effect on non-irradiated adult trout which swam with trout irradiated as YSL or first feeders., Conclusions: When put in context with the proteomic changes observed in these fish we propose the increased copper uptake in adult trout irradiated as eggs at 48 h after fertilization could be part of an anti-tumorigenic response and the increase in copper uptake in adult trout irradiated as first feeders could be part of a potentially protective pro-apoptotic response. Similarly we propose the increase in copper uptake in non-irradiated adult trout, induced by trout irradiated as eggs at 48 h after fertilization or as eyed eggs, was part of the universally anti-tumorigenic nature of the X-ray induced bystander effect in fish. However this was exclusive to embryonic irradiation.

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: A major issue in radiotherapy is the relative resistance of hypoxic cells to radiation. Historic approaches to this problem include the use of oxygen mimetic compounds to sensitize tumour cells, which were unsuccessful. This review looks at modern approaches aimed at increasing the efficacy of targeting and radiosensitizing hypoxic tumour microenvironments relative to normal tissues and asks the question of whether non-targeted effects in radiobiology may provide a new "target". Novel techniques involve the integration of recent technological advancements such as nanotechnology, cell manipulation, and medical imaging. Particularly, the major areas of research discussed in this review include tumour hypoxia imaging through PET imaging to guide carbogen breathing, gold nanoparticles, macrophage-mediated drug delivery systems used for hypoxia-activate prodrugs, and autophagy inhibitors. Furthermore, this review outlines several features of these methods, including the mechanisms of action to induce radiosensitization, the increased accuracy in targeting hypoxic tumour microenvironments relative to normal tissue, preclinical/clinical trials, and future considerations., Conclusions: This review suggests that the four novel tumour hypoxia therapeutics demonstrate compelling evidence that these techniques can serve as powerful tools to increase targeting efficacy and radiosensitizing hypoxic tumour microenvironments relative to normal tissue. Each technique uses a different way to manipulate the therapeutic ratio, which we have labelled "oxygenate, target, use, and digest". In addition, by focusing on emerging non-targeted and out-of-field effects, new umbrella targets are identified, which instead of sensitizing hypoxic cells, seek to reduce the radiosensitivity of normal tissues.

Purpose: The main goal of the research was to determine whether commercially available common dietary phytochemical supplements (curcumin, andrographolide, and d-limonene) have radiomodulatory effects on p53-competent human colonic epithelial cells., Methods: Clonogenic survival assays were used to characterize effects of the phytochemicals on cultured colonic epithelial cells (HCT116 p53 +/+ ) in direct irradiation or upon receipt of irradiated-cell conditioned media (for bystander effects). In direct irradiation, feeding regimen experiments included compound administration pre- and post-irradiation, which was used as a basis to define effects as radioprotective and radiomitigative, respectively. In the bystander effect experiments, either donor or recipient cell cultures were fed with the phytochemicals and bystander-induced clonogenic cell death was quantitatively evaluated. Dose challenge was in the range of 0.5 - 5 Gy using the gamma source (Cs-137)., Results: Curcumin, andrographolide, and d-limonene appeared to not exhibit radioprotective and radiomitigative properties in HCT116 p53 +/+ cells. D-limonene was found to induce radiosensitization in post-irradiation administration. All three compounds appeared not to modulate the radiation-induced bystander signal production and response in HCT116 p53 +/+ cells., Conclusions: Curcumin, andrographolide, and d-limonene are known to have many chemoprotective benefits. This work shows that they, however, did not protect colonic epithelial HCT116 p53 +/+ cells from radiation killing. As HCT116 p53 +/+ cells are tumourigenic in nature, this finding implies that these three dietary compounds would not reduce the killing efficacy of radiation in gastrointestinal tumorigenesis. The post-irradiation radiosensitizing effect of d-limonene was an intriguing observation worth further investigation.

Objectives: This review aims to trace the historical narrative surrounding the low dose effects of radiation on the immune system and how our understanding has changed from the beginning of the 20th century to now. The particular focus is on the non-targeted effects (NTEs) of low dose ionizing radiation (LDIR) which are effects that occur when irradiated cells emit signals that cause effects in the nearby or distant non-irradiated cells known as radiation induced bystander effect (RIBE). Moreover, radiation induced genomic instability (RIGI) and abscopal effect (AE) also regarded as NTE. This was prompted by our recent discovery that ultraviolet A (UVA) photons are emitted by the irradiated cells and that these photons can trigger NTE such as the RIBE in unirradiated recipients of these photons. Given the well-known association between UV radiation and the immune response, where these biophotons may pose as bystander signals potentiating processes in deep tissues as a consequence of LDIR, it is timely to review the field with a fresh lens. Various pathways and immune components that contribute to the beneficial and adverse types of modulation induced by LDR will also be revisited., Conclusion: There is limited evidence for LDIR induced immune effects by way of a non-targeted mechanism in biological tissue. The literature examining low to medium dose effects of ionizing radiation on the immune system and its components is complex and controversial. Early work was compromised by lack of good dosimetry while later work mainly looks at the involvement of immune response in radiotherapy. There is a lack of research in the LDIR/NTE field focusing on immune response although bone marrow stem cells and lineages were critical in the identification and characterization of NTE where effects like RIGI and RIBE were heavily researched. This may be in part, a result of the difficulty of isolating NTE in whole organisms which are essential for good immune response studies. Models involving inter organism transmission of NTE are a promising route to overcome these issues.

In the Fall of 2016 a workshop was held which brought together over 50 scientists from the ecological and radiological fields to discuss feasibility and challenges of reintegrating ecosystem science into radioecology. There is a growing desire to incorporate attributes of ecosystem science into radiological risk assessment and radioecological research more generally, fueled by recent advances in quantification of emergent ecosystem attributes and the desire to accurately reflect impacts of radiological stressors upon ecosystem function. This paper is a synthesis of the discussions and consensus of the workshop participant's responses to three primary questions, which were: 1) How can ecosystem science support radiological risk assessment? 2) What ecosystem level endpoints potentially could be used for radiological risk assessment? and 3) What inference strategies and associated methods would be most appropriate to assess the effects of radionuclides on ecosystem structure and function? The consensus of the participants was that ecosystem science can and should support radiological risk assessment through the incorporation of quantitative metrics that reflect ecosystem functions which are sensitive to radiological contaminants. The participants also agreed that many such endpoints exit or are thought to exit and while many are used in ecological risk assessment currently, additional data need to be collected that link the causal mechanisms of radiological exposure to these endpoints. Finally, the participants agreed that radiological risk assessments must be designed and informed by rigorous statistical frameworks capable of revealing the causal inference tying radiological exposure to the endpoints selected for measurement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This short review explores the utility and applications of CRISPR/Cas9 systems in radiobiology. Specifically, in the context of experimentally simulating genotoxic effects of Ionizing Radiation (IR) to determine the contributions from DNA targets and 'Complex Double-Stranded Breaks' (complex DSBs) to the IR response. To elucidate this objective, this review considers applications of CRISPR/Cas9 on nuclear DNA targets to recognize the respective 'nucleocentric' response. The article also highlights contributions from mitochondrial DNA (mtDNA) - an often under-recognized target in radiobiology. This objective requires accurate experimental simulation of IR-like effects and parameters with the CRISPR/Cas9 systems. Therefore, the role of anti-CRISPR proteins in modulating enzyme activity to simulate dose rate - an important factor in radiobiology experiments is an important topic of this review. The applications of auxiliary domains on the Cas9 nuclease to simulate oxidative base damage and multiple stressor experiments are also topics of discussion. Ultimately, incorporation of CRISPR/Cas9 experiments into computational parameters in radiobiology models of IR damage and shortcomings to the technology are discussed as well. Altogether, the simulation of IR parameters and lack of damage to non-DNA targets in the CRISPR/Cas9 system lends this rapidly emerging tool as an effective model of IR induced DNA damage. Therefore, this literature review ultimately considers the relevance of complex DSBs to radiobiology with respect to using the CRISPR/Cas9 system as an effective experimental tool in models of IR induced effects., Competing Interests: Declaration of Competing Interest The author(s) declared no conflicts of interest with respect to the research, authorship and/or publication of this article., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Following large-scale nuclear power plant accidents such as those that occurred at Chernobyl (Ukraine) in 1986 and Fukushima Daiichi (Japan) in 2011, large populations are living in areas containing residual amounts of radioactivity. As a key session of the ConRad conference, experts were invited from different disciplines to provide state-of-the-art information on the topic of "living in contaminated areas." These experts provided their different perspectives on a range of topics including radiation protection principles and dose criteria, environmental measurements and dose estimation, maintaining decent living and working conditions, evidence of health risks, and social impact and risk communication. A short summary of these different perspectives is provided in this paper.

This short review explores the utility and applications of CRISPR/Cas9 systems in radiobiology. Specifically, in the context of experimentally simulating genotoxic effects of Ionizing Radiation (IR) to determine the contributions from DNA targets and 'Complex Double-Stranded Breaks' (complex DSBs) to the IR response. To elucidate this objective, this review considers applications of CRISPR/Cas9 on nuclear DNA targets to recognize the respective 'nucleocentric' response. The article also highlights contributions from mitochondrial DNA (mtDNA) - an often under-recognized target in radiobiology. This objective requires accurate experimental simulation of IR-like effects and parameters with the CRISPR/Cas9 systems. Therefore, the role of anti-CRISPR proteins in modulating enzyme activity to simulate dose rate - an important factor in radiobiology experiments is an important topic of this review. The applications of auxiliary domains on the Cas9 nuclease to simulate oxidative base damage and multiple stressor experiments are also topics of discussion. Ultimately, incorporation of CRISPR/Cas9 experiments into computational parameters in radiobiology models of IR damage and shortcomings to the technology are discussed as well. Altogether, the simulation of IR parameters and lack of damage to non-DNA targets in the CRISPR/Cas9 system lends this rapidly emerging tool as an effective model of IR induced DNA damage. Therefore, this literature review ultimately considers the relevance of complex DSBs to radiobiology with respect to using the CRISPR/Cas9 system as an effective experimental tool in models of IR induced effects., Competing Interests: Declaration of Competing Interest The author(s) declared no conflicts of interest with respect to the research, authorship and/or publication of this article., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

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.

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.

Neutron radiation is very harmful to both individual organisms and the environment. A n understanding of all aspects of both direct and indirect effects of radiation is necessary to accurately assess the risk of neutron radiation exposure. This review seeks to review current evidence in the literature for radiation-induced bystander effects and related effects attributable to neutron radiation. It also attempts to determine if the suggested evidence in the literature is sufficient to justify claims that neutron-based radiation can cause radiation-induced bystander effects. Lastly, the present paper suggests potential directions for future research concerning neutron radiation-induced bystander effects. Data was collected from studies investigating radiation-induced bystander effects and was used to mathematically generate pooled datasets and putative trends; this was done to potentially elucidate both the appearance of a conventional trend for radiation-induced bystander effects in studies using different types of radiation. Furthermore, literature review was used to compare studies utilizing similar tissue models to determine if neutron effects follow similar trends as those produced by electromagnetic radiation. We conclude that the current understanding of neutron-attributable radiation-induced bystander effects is incomplete. Various factors such as high gamma contamination during the irradiations, unestablished thresholds for gamma effects, different cell lines, energies, and different dose rates affected our ability to confirm a relationship between neutron irradiation and RIBE, particularly in low-dose regions below 100 mGy. It was determined through meta-analysis of the data that effects attributable to neutrons do seem to exist at higher doses, while gamma effects seem likely predominant at lower dose regions. Therefore, whether neutrons can induce bystander effects at lower doses remains unclear. Further research is required to confirm these findings and various recommendations are made to assist in this effort. With these recommendations, we hope that research conducted in the future will be better equipped to explore the indirect effects of neutron radiation as they pertain to biological and ecological phenomena., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Exposures to ionizing radiation can cause depletion in stem cell reservoirs and lead to chronic injury processes that exacerbate carcinogenic and inflammatory responses. Therefore, radioprotective measures, against both acute and chronic biological effects of radiation, require frequent intake of nontoxic natural products, which have practical oral administration. The goal of this study was to characterize the radioprotective, radiomitigative and radiation-induced bystander effect-inhibiting properties of endogenous metabolites: phenylacetate, ursodeoxycholate and tauroursodeoxycholate. Compounds were administered pre- and postirradiation as well as in donor and recipient bystander flasks to analyze whether these might adequately protect against radiation injury as well as facilitate recovery from the exposures. The clonogenic HCT116 p53 wild-type cancer cell line in this study shares characteristics of stem cells, such as high reproductive viability, which is an effective marker to demonstrate compound effectiveness. Clonogenic assays were therefore used to characterize radioprotective, radiomitigative and bystander inhibiting properties of treatment compounds whereby cellular responses to radiation were quantified with macroscopic colony counts to measure cell survival in flasks. The results were statistically significant for phenylacetate and tauroursodeoxycholate when administered preirradiation, conferring radioprotection up to 2 Gy, whereas administration postirradiation and in bystander experiments did not confer radioprotection in vitro . These findings suggest that phenylacetate and tauroursodeoxycholate might be effective radioprotectors, although they possess no radiomitigative properties.

This reflection aims to look at the evolution of thinking about radiation dose response relationships from the early years of the journal when target theory prevailed to the present day when dose response is seen as a more holistic process involving multiple levels of organization and communication. The review is structured to consider how the old ideas evolved leading to apparently abrupt paradigm shifts. The odd data leading to these conceptual shifts are reviewed. Topics, which are currently still not mainstream are considered with a view to how they may change the future of radiobiology. Finally some personal reflections on the insights gained during the writing of the review are presented. The major conclusion from this study is that ideas concerning survival curves and radiation dose responses evolved and (epi)mutated gradually, driven in a large part by the techniques available for studying radiobiological processes. The illusion of abrupt paradigm shifts is not really borne out by the history when primary references are studied rather than textbooks or reviews. The textbooks necessarily simplify and distil complex data to provide a 'take-home message' while reviews are usually very personal collations selected among the vast amount of scientific literature. Primary references reveal the context of the discussion and the caveats and uncertainties of the authors.

Purpose: To reflect on the contributions of R. H. Mole to radiobiology. Robin Mole was a very active radiobiologist when the IJRB was first established and had two papers in the first few issues of the journal in 1959. Conclusions: R. H. Mole made significant contributions to radiobiology and is particularly associated with studies of the effects of low dose exposures on the reproductive health of mammals. Many of his ideas are still debated and remain controversial.

Background and Objectives: Rare but potentially life-threatening hypersensitivity reactions can occur during the administration of intravenous iron. To provide guidance to healthcare professionals caring for adults receiving intravenous iron, a panel of 10 Canadian clinical experts developed a practical algorithm for the identification and management of hypersensitivity reactions to intravenous iron., Materials and Methods: A systematic search of PubMed to February 2018 was performed. Articles related to hypersensitivity reactions were selected for review. The algorithm was developed during a 1-day live meeting based on the literature review and clinical expertise where evidence was lacking. The algorithm was then refined through an iterative process involving a web-based platform and virtual meetings., Results: The algorithm provides guidance to healthcare professionals in preparing for and administering IV iron, as well as recognizing and managing hypersensitivity reactions to intravenous iron. Considerations for re-challenging patients who have experienced prior reactions are provided., Conclusion: Healthcare professionals who are involved in the care of patients receiving intravenous iron should be trained to anticipate, recognize and manage hypersensitivity reactions to intravenous iron to optimize patient care., (© 2019 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Radiation-induced bystander effects refer to the production of signals from irradiated cells which induce responses in unirradiated, or bystander, cells. There has been a recent resurgence of interest in low-energy photon biology. This is due to concerns about health effects, increased use of biophoton imaging techniques, and the fact that biophotons can act as a bystander signal. This review discusses the history of light signaling in biology and potential mechanisms involved in the generation and transduction of signaling mechanisms. The role of photons in signaling in the animal and plant kingdoms is also reviewed. Finally, the potential to harness these mechanisms in radiation protection or therapy is discussed with emphasis on promising future directions for research., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Contrary to the effects of high doses of radiation, the effects of low doses of radiation are still being investigated. Low doses and their non-targeted effects in particular are of special interest for researchers. The accident that occurred at the Chernobyl Nuclear Power Plant (NPP) gives researchers the opportunity to view these effects outside of a laboratory environment. For this paper, the relationship between low historic radiation doses and the persistent genetic damage observed in populations of fruit flies (Drosophila melanogaster) around the Chernobyl NPP over 3 years will be investigated. Data from Zainullin et al. (1992) on the frequency of sex-linked recessive lethals (SLRLs) in D. melanogaster around the Chernobyl NPP. To calculate the absorbed historic external dose, a method based on the Gaussian plume model was used to find the external dose from both plume shine and ground shine. The dose attributed to the ground shine dose made a greater contribution to the overall absorbed external historic radiation dose than the plume shine dose. For earlier generations of Drosophila living in the radioactive contaminated sites, the SLRL frequencies appeared to correlate with the dose in a linear no-threshold relationship. The later descendent generations appeared to have developed a radio-adaptive-like response. This work contributes to the understanding of historic dose effects on wildlife health following the accidental release of high mount of radioactive materials into the environment., (Copyright © 2019 Elsevier Inc. All rights reserved.)