The fear of radiation has been present almost since the discovery of radiation, but has intensified since the "dawn of the atomic age" over 75 y ago. This fear has often served as an impediment to ...the safe and beneficial uses of radiation and radioactive material. The underlying causes of such fear are varied, can be complex, and are often not associated with any scientific knowledge or understanding. The authors believe that a clear understanding of the current scientific knowledge and understanding of the effects of radiation exposure may be useful in helping to allay some of the fear of radiation. This manuscript attempts to (1) address several scientific questions that we believe have contributed to the fear of radiation, (2) review the data derived from research that can be used to address these questions, and (3) summarize how the results of such scientific research can be used to help address the fear of low-dose and low-dose-rate radiation. Several examples of how fear of radiation has affected public perception of radiological events are discussed, as well as a brief history of the etiology of radiation fear. Actions needed to reduce the public fear of radiation and help fulfill the full societal benefits of radiation and radioactive materials are suggested.
FLASH radiotherapy is a novel technique that has been shown in numerous preclinical in vivo studies to have the potential to be the next important improvement in cancer treatment. However, the ...biological mechanisms responsible for the selective FLASH sparing effect of normal tissues are not yet known. An optimal translation of FLASH radiotherapy into the clinic would require a good understanding of the specific beam parameters that induces a FLASH effect, environmental conditions affecting the response, and the radiobiological mechanisms involved. Even though the FLASH effect has generally been considered as an in vivo effect, studies finding these answers would be difficult and ethically challenging to carry out solely in animals. Hence, suitable in vitro studies aimed towards finding these answers are needed. In this review, we describe and summarise several in vitro assays that have been used or could be used to finally elucidate the mechanisms behind the FLASH effect.
Colorectal cancer is the most commonly reported gastrointestinal malignancy, with a recent, rapid increase of the annual incidence all over the world. Enhancing the radiosensitivity of cancer cells ...while preserving the health of normal cells is one of the most important tasks in clinical radiobiology. However, resistance to radiotherapy for colorectal cancer greatly decreases the therapeutic outcome. Melatonin (
-acetyl-5-methoxytryptamine), a natural secretory product that the pineal gland in the brain normally produces, has been reported to have anticancer properties. In the study, we investigated the combination of melatonin with radiotherapy as a treatment for colorectal cancer. We firstly explored the anti-tumor activity of melatonin combined with ionizing radiation (IR) against colorectal carcinoma in vitro. It was found that melatonin effectively inhibited human colorectal carcinoma cell line HCT 116 cellular proliferation, colony formation rate and cell migration counts following IR. Increasing the radiosensitivity of colorectal cancer cells by melatonin treatment was found to be associated with cell cycle arrest in the G2/M phase, downregulation of proteins involved in DNA double-strand break repair and activation of the caspase-dependent apoptotic pathway. Moreover, we also investigated the combined effect of IR and melatonin on colorectal tumor in vivo. Results from a tumor xenograft showed that melatonin plus IR treatment significantly suppressed tumor cell growth compared with melatonin or IR alone, resulting in a much higher tumor inhibition rate for the combined treatment. The data suggested that melatonin combined with IR could improve the radiosensitivity of colorectal cancer and thus enhance the therapeutic effect of the patients, implying melatonin could function as a potential sensitizer in tumor radiotherapy.
The evolution of SARS-CoV-2 pneumonia to acute respiratory distress syndrome is linked to a virus-induced “cytokine storm”, associated with systemic inflammation, coagulopathies, endothelial damage, ...thrombo-inflammation, immune system deregulation and disruption of angiotensin converting enzyme signaling pathways. To date, the most promising therapeutic approaches in COVID-19 pandemic are linked to the development of vaccines. However, the fight against COVID-19 pandemic in the short and mid-term cannot only rely on vaccines strategies, in particular given the growing proportion of more contagious and more lethal variants among exposed population (the English, South African and Brazilian variants). As long as collective immunity is still not acquired, some patients will have severe forms of the disease. Therapeutic perspectives also rely on the implementation of strategies for the prevention of secondary complications resulting from vascular endothelial damage and from immune system deregulation, which contributes to acute respiratory distress and potentially to long term irreversible tissue damage. While the anti-inflammatory effects of low dose irradiation have been exploited for a long time in the clinics, few recent physiopathological and experimental data suggested the possibility to modulate the inflammatory storm related to COVID-19 pulmonary infection by exposing patients to ionizing radiation at very low doses. Despite level of evidence is only preliminary, these preclinical findings open therapeutic perspectives and are discussed in this article.
We present here an overview of the topics presented and discussed during the Working Group 4 sessions of the European Advanced Accelerator Concepts workshop 2019 (EAAC19). The remit of Working Group ...4 (WG4) is to address topics relating to all potential application areas of compact and high-gradient accelerators. This includes recent experimental results and planned demonstration experiments with relevance to radiation generation, medical, industrial, and cultural heritage sector applications, and development of advanced photon sources such as free electron lasers (FEL). Within scope of Working Group 4 is also discussions on planned facilities implementing advanced accelerator concepts that have a focus on applications, as well as beam shaping and tailoring to deliver adequate beams for applications. The topics discussed in the EAAC19 programme for Working Group 4 all fit within the following application theme areas: 1) new facilities exploiting advanced and novel accelerator concepts, 2) development of next generation photon sources, 2) imaging and spectroscopy with laser-plasma accelerator particle and photon beams, and 3) radiobiology with laser-plasma accelerator particle beams.
A new proton beam-line dedicated to R&D programs has been developed at CentreAntoine Lacassagne (CAL), in Nice (France), in collaboration with the Centrenational d'études spatiales (CNES). This is ...the second beam-line of the MEDICYC 65 MeV cyclotron that is currently in operation, the first being the clinical ‘eye-line’ used for ocular proton therapy. The R&D beam-line is proposed with two configurations, the first producing a Gaussian narrow beam of a few mm width, the second a 100 mm diameter flat beam with a homogeneity better than ±3%. The energy range is (20 - ∼60) MeV, where the exact upper limit depends on the beam configuration being used. The energy spread of the non-degraded beam is (0.3 ± 0.1) MeV. A beam current between 10 pA and 10 μA can be produced with a stability better than 0.2% above 100 pA, and 2% below. The beam can be monitored online at a precision better than 5% in the flux range 1E5 (1E6) – 1E9 (1E10) p/cm2/s for a flat (Gaussian) configuration, although work is in progress to extend this range. Targeted applications for the R&D beam-line are instrumentation research, radiation tolerance tests of components and radiobiology.
•A high-availability 60 MeV proton beam-line dedicated for R&D is operational.•The beam-line can provide a 100 mm homogenous beam over a large flux interval.•Alternatively, a Gaussian beam of a few mm standard deviation can be produced.•The beam-line has been designed for radiation tolerance tests, instrumentation R&D and research in radiobiology.
In the last years, radiofrequency (RF) has demonstrated that it can reduce DNA damage induced by a subsequent treatment with chemical or physical agents in different cell types, resembling the ...adaptive response, a phenomenon well documented in radiobiology. Such an effect has also been reported by other authors both in vitro and in vivo, and plausible hypotheses have been formulated, spanning from the perturbation of the cell redox status, to DNA repair mechanisms, and stress response machinery, as possible cellular mechanisms activated by RF pre-exposure. These mechanisms may underpin the observed phenomenon, and require deeper investigations. The present study aimed to determine whether autophagy contributes to RF-induced adaptive response. To this purpose, SH-SY5Y human neuroblastoma cells were exposed for 20 h to 1950 MHz, UMTS signal, and then treated with menadione. The results obtained indicated a reduction in menadione-induced DNA damage, assessed by applying the comet assay. Such a reduction was negated when autophagy was inhibited by bafilomycin A1 and E64d. Moreover, CRISPR SH-SY5Y cell lines defective for ATG7 or ATG5 genes did not show an adaptive response. These findings suggest the involvement of autophagy in the RF-induced adaptive response in human neuroblastoma cells; although, further investigation is required to extend such observation at the molecular level.
Until the development of single cell gel electrophoresis methods in the 1980s, measurement of radiation-induced DNA strand breaks in individual cells was limited to detection of micronuclei or ...chromosome breaks that measured the combined effects of exposure and repair. Development of methods to measure the extent of migration of DNA from single cells permitted detection of initial radiation-induced DNA breaks present in each cell. As cells need not be radiolabeled, there were new opportunities for analysis of radiation effects on cells from virtually any tissue, provided a single cell suspension could be prepared. The comet assay (as this method was subsequently named) was able to measure, for the first time, the fraction of radiobiologically hypoxic cells in mouse and human tumors. It was used to determine that the rate of rejoining of DNA breaks was relatively homogenous within an irradiated population of cells. Because individual cells were analyzed, heavily damaged or apoptotic cells could be identified and eliminated from analysis to determine “true” DNA strand break rejoining rates. Other examples of applications of the comet assay in radiobiology research include analysis of the inter-individual differences in response to radiation, effect of hypoxia modifying agents on tumor hypoxic fraction, the role of cell cycle position during DNA break induction and rejoining, non-targeted effects on bystander cells, and effects of charged particles on DNA fragmentation patterns.
Despite the international 3Rs principles that recommends replacing, reducing and refining the use of animals in medical experimentation, it remains difficult to obtain funding in Canada for medical ...research that respects these principles, particularly with regard to replacement. This observation led our team to review the literature on the arguments for and against animal experimentation in the fields of oncology and radiobiology. This article presents a synthesis of these arguments. Using the method created by McCullough and colleagues to conduct critical reviews of the ethics literature, we analysed 25 texts discussing the arguments for and against animal experimentation in oncology and radiobiology. Six broad categories of arguments for animal experimentation and eleven categories of arguments against it emerged from our analyses. Furthermore, the arguments against animal testing are more convincing from both an empirical and normative perspective. Also, most arguments obtained are transferable in other fields of medicine. In addition to the literature review, a critical reflection was conducted and other arguments were discussed. It seems that a conservative culture persists in medical research, despite the scientific evidence and ethical arguments to the contrary.
PDF
