ALTERNATIVE MEDICINE TECHNIQUES HAVE NON-LINEAR EFFECTS ON RADIATION RESPONSE AND CAN ALTER THE EXPRESSION OF RADIATION INDUCED BYSTANDER EFFECTS

Many so-called “alternative medicine” techniques such as Reiki and acupuncture produce very good outcomes for intractable pain and other chronic illnesses but the efficacy is often dismissed as being psychosomatic. However a plausible mechanism does exist i.e. that the treatments alter the electromagnetic fields in living organisms and thereby prevent or reduce activity of neurons which lead to the pain. Low doses of ionising radiation have similar effects on electromagnetic fields and are known to induce signaling cascades in tissues due to ion gradients. To test this hypothesis cell cultures were exposed to Reiki – like and to acupuncture – like treatments, both performed by qualified practitioners. The cells were exposed either before or after the treatment to x-rays and were monitored for production of direct damage or bystander signals. The data suggest that the alternative techniques altered the response of cells to direct irradiation and altered bystander signal mechanisms. We conclude that alternative medicine techniques involving electromagnetic perturbations may modify the response of cells to ionizing radiation. In addition to the obvious implications for mechanistic studies of low dose effects, this could provide a novel target to exploit in radiation protection and in optimizing therapeutic gain during radiotherapy

Identification of Key Proteins in Human Epithelial Cells Responding to Bystander Signals From Irradiated Trout Skin

Radiation-induced bystander signaling has been found to occur in live rainbow trout fish (Oncorhynchus mykiss). This article reports identification of key proteomic changes in a bystander reporter cell line (HaCaT) grown in low-dose irradiated tissue-conditioned media (ITCM) from rainbow trout fish. In vitro explant cultures were generated from the skin of fish previously exposed to low doses (0.1 and 0.5 Gy) of X-ray radiation in vivo. The ITCM was harvested from all donor explant cultures and placed on recipient HaCaT cells to observe any change in protein expression caused by the bystander signals. Proteomic methods using 2-dimensional (2D) gel electrophoresis and mass spectroscopy were employed to screen for novel proteins expressed. The proteomic changes measured in HaCaT cells receiving the ITCM revealed that exposure to 0.5 Gy induced an upregulation of annexin A2 and cingulin and a downregulation of Rho-GDI2, F-actin-capping protein subunit beta, microtubule-associated protein RP/EB family member, and 14-3-3 proteins. The 0.1 Gy dose also induced a downregulation of Rho-GDI2, hMMS19, F-actin-capping protein subunit beta, and microtubule-associated protein RP/EB family member proteins. The proteins reported may influence apoptotic signaling, as the results were suggestive of an induction of cell communication, repair mechanisms, and dysregulation of growth signal

Altered mitochondrial function and genome frequency post exposure to γ-radiation and bystander factors

PURPOSE: To further evaluate irregular mitochondrial function and mitochondrial genome damage induced by direct γ-irradiation and bystander factors in human keratinocyte (HPV-G) epithelial cells and hamster ovarian fibroblast (CHO-K1) cells. This is as a follow-up to our recent reports of γ-irradiation-induced loss of mitochondrial function and mitochondrial DNA (mtDNA) damage

A Dose Threshold for a Medium Transfer Bystander Effect for a Human Skin Cell Line

The existence of radiation-induced bystander effects mediated by diffusible factors is now accepted but the mechanisms and precise behavior at low doses remain unclear. We exposed cells to gamma doses in the range 0.04 mGy – 5 Gy, harvested the culture medium and transferred it to unirradiated reporter cells. Calcium fluxes and clonogenic survival were measured in the recipients. We show evidence for a dose threshold around 2 mGy for the human skin cell line used with a suggestion of increased survival below that dose. Similar experiments using direct gamma irradiation showed no reduction in survival until the dose exceeded 7 mGy. Preliminary data for neutrons where the gamma dose was kept below the bystander threshold, does not show significant bystander effect in the dose range 1 – 33 mGy. A lack of a bystander response with neutrons occurred at high dose around 1 Gy where significant cell killing from direct irradiation was observed. The result may have implications for understanding the role of bystander effects at low doses

TRANSMISSION OF SIGNALS FROM RATS RECEIVING HIGH DOSES OF MICROBEAM RADIATION TO CAGE MATES: AN INTER-MAMMAL BYSTANDER EFFECT

Inter-animal signaling from irradiated to non-irradiated organisms has been demonstrated for whole body irradiated mice and also for fish. The aim of the current study was to look at radiotherapy style limited exposure to part of the body using doses relevant in preclinical therapy. High dose homogenous field irradiation and the use of irradiation in the microbeam radiation therapy mode at the European Synchrotron Radiation Facility (ESRF) at Grenoble was tested by giving high doses to the right brain hemisphere of the rat. The right and left cerebral hemispheres and the urinary bladder were later removed to determine whether abscopal effects could be produced in the animals and also whether effects occurred in cage mates housed with them. The results show strong bystander signal production in the contra-lateral brain hemisphere and weaker effects in the distant bladder of the irradiated rats. Signal strength was similar or greater in each tissue in the cage mates housed for 48hrs with the irradiated rats. Our results support the hypothesis that proximity to an irradiated animal induces signalling changes in an unirradiated partner. If similar signaling occurs between humans, the results could have implications for caregivers and hospital staff treating radiotherapy patients

When a duck is not a duck; a new interdisciplinary synthesis for environmental radiation protection

This consensus paper presents the results of a workshop held in Essen, Germany in September 2017, called to examine critically the current approach to radiological environmental protection. The meeting brought together participants from the field of low dose radiobiology and those working in radioecology. Both groups have a common aim of identifying radiation exposures and protecting populations and individuals from harmful effects of ionising radiation exposure, but rarely work closely together. A key question in radiobiology is to understand mechanisms triggered by low doses or dose rates, leading to adverse outcomes of individuals while in radioecology a key objective is to recognise when harm is occurring at the level of the ecosystem. The discussion provided a total of six strategic recommendations which would help to address these questions.Funding was provided for this workshop by the International Union for Radioecology and the University of Duisburg-Essen

Addressing ecological effects of radiation on populations and ecosystems to improve protection of the environment against radiation: Agreed statements from a Consensus Symposium

This paper reports the output of a consensus symposium organized by the International Union of Radioecology in November 2015. The symposium gathered an academically diverse group of 30 scientists to consider the still debated ecological impact of radiation on populations and ecosystems. Stimulated by the Chernobyl and Fukushima disasters' accidental contamination of the environment, there is increasing interest in developing environmental radiation protection frameworks. Scientific research conducted in a variety of laboratory and field settings has improved our knowledge of the effects of ionizing radiation on the environment. However, the results from such studies sometimes appear contradictory and there is disagreement about the implications for risk assessment. The Symposium discussions therefore focused on issues that might lead to different interpretations of the results, such as laboratory versus field approaches, organism versus population and ecosystemic inference strategies, dose estimation approaches and their significance under chronic exposure conditions. The participating scientists, from across the spectrum of disciplines and research areas, extending also beyond the traditional radioecology community, successfully developed a constructive spirit directed at understanding discrepancies. From the discussions, the group has derived seven consensus statements related to environmental protection against radiation, which are supplemented with some recommendations. Each of these statements is contextualized and discussed in view of contributing to the orientation and integration of future research, the results of which should yield better consensus on the ecological impact of radiation and consolidate suitable approaches for efficient radiological protection of the environment.Keywords: Consensus development, Environmental protection, Populations, Radiation effects, Ecosystems, Ecological risk assessmen

Causes of genome instability: the effect of low dose chemical exposures in modern society.

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis

Development of an In Vivo Assay for Detection of Non-Targeted Radiation Effects

An adaptive response may be defined as the effect of a small priming dose of radiation modifying the anticipated cellular response of the same tissues so as to alter the predicted response to a larger dose of radiation. We and others have demonstrated that at low radiation doses (less than 0.5 Gy) the lethal and mutational effect of the radiation is mainly, possibly entirely, due to the non-targeted effects. This is the dose range for priming doses in adaptive response protocols. In an associated presentation from our group, we demonstrate that the adaptive response may be explicable as a non targeted (bystander) response. In this paper we present data from exposed human patients, showing that a simple assay using blood can demonstrate variation in the extent and type of non-targeted effects and that exposure to radiation can modulate the subsequent non-targeted response to a later dose. Patients undergoing radiotherapy treatment for cancer gave blood samples immediately after the first dose, midway during and six weeks after therapy. The serum from these samples was harvested, diluted in tissue culture medium and added to reporter cells. The toxicity or growth promoting activity of the serum was measured using a clonogenic assay coupled with immunocytochemical measurement of various proteins involved in apoptosis or growth. There is already evidence that bystander effects are controlled by both genetic and epigenetic (lifestyle) factors. These data could support the development of a simple blood based assay to predict overall response of human subjects to low doses of radiation taking all the low dose factors into account

Editorial.

The development and implementation of a universal, evidence-based radiation protection policy is one of the greatest challenges that we face. While different contexts and unique situations make the implementation of a global policy complex, the idea that there might be a commonly accepted set of principles around which regulation, legislation and monitoring might be built has long been accepted as desirable, if not even essential. Recent developments in radiation protection and in radiobiology have started to suggest that the current, anthropocentric approach may underestimate the impact of radiation on the environment. This, through ecosystem perturbations, may prove deleterious to humans as well as other species in a way not captured by assessing human cancer risk as the main endpoint under consideration. Our evolving understanding of other human endpoints such as cardiovascular disease and the impact of multiple stressors such as pesticides and heavy metals have started to broaden our concept of an endpoint for human radiation protection and in doing so start to draw in the importance of the non-radioactive anthropogenic and natural environments. The questions raised by considering non-medical radiation protection as primarily an issue of environmental protection, stimulated a recent discussion and accompanying paper in IJRB (Mothersill et al. 2020) and were the stimulus for this special issue