Radiation, Volume 2, Issue 1 (March 2022) – 11 articles

In mammalian cells, genomic DNA is packaged with histone proteins and condensed into chromatin. To gain access to the DNA, chromatin remodelling is required that is enhanced through histone post-translational modifications, which subsequently stimulate processes including DNA repair and transcription. Histone acetylation is one of the most well understood modifications and is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). These enzymes play critical roles in normal cellular functioning, and the dysregulation of HDAC expression in particular has been linked with the development of a number of different cancer types. Conversely, tumour cell killing following radiotherapy is triggered through DNA damage and HDACs can help co-ordinate the cellular DNA damage response which promotes radioresistance. Consequently, HDAC inhibitors have been investigated as potential radiosensitizers in vitro and in vivo to improve the efficacy or radiotherapy in specific tumour types. In this review, we provide an up-to-date summary of HDACs and their cellular functions, including in DNA damage repair. We also review evidence demonstrating that HDAC inhibitors can effectively enhance tumour radiosensitisation, and which therefore show potential for translation into the clinic for cancer patient benefit. Full article

Interest in combining metallic nanoparticles, such as iron (SPIONs), gold (AuNPs) and bismuth oxide (BiONPs), with radiotherapy has increased due to the promising therapeutic advantages. While the underlying physical mechanisms of NP-enhanced radiotherapy have been extensively explored, only a few research works were motivated to quantify its contribution in an experimental dosimetry setting. This work aims to explore the feasibility of radiochromic films to measure the physical dose enhancement (DE) caused by the release of secondary electrons and photons during NP–radiotherapy interactions. A 10 mM each of SPIONs, AuNPs or BiONPs was loaded into zipper bags packed with GAFCHROMIC™ EBT3 films. The samples were exposed to a single radiation dose of 4.0 Gy with clinically relevant beams. Scanning was conducted using a flatbed scanner in red-component analysis for optimum sensitivity. Experimental dose enhancement factors (DEF_Experimental) were then calculated using the ratio of absorbed doses (with/without NPs) converted from the films’ calibration curves. DEF_Experimental for all NPs showed no significant physical DE beyond the uncertainty limits (p > 0.05). These results suggest that SPIONs, AuNPs and BiONPs might potentially enhance the dose in these clinical beams. However, changes in NPs concentration, as well as dosimeter sensitivity, are important to produce observable impact. Full article

High-throughput omics platforms have pioneered our approach to understanding biological and cellular processes. Omics technologies provide powerful tools for studying various molecules, such as genes, proteins, and metabolites, in a particular state and at a particular time. Although omics has had a presence in the radiation community for more than 3 decades, the use of it is still in its infancy. Omics studies enable radiation researchers to understand the molecular mechanism underlying the biological effects of radiation exposure on normal and cancerous tissues, and to answer critical questions such as individual sensitivity, risk assessment, and biomarker discovery. In this commentary, we take a look back at the omics studies that have been conducted in radiation research in the last 20 years and discuss whether omics has fulfilled expectations by examining the knowledge and research gaps in radiation omics. Full article

Proteins play a key role in living organisms. The study of proteins and their dynamics provides information about their functionality, catalysis and potential alterations towards pathological diseases. Several techniques are used for studying protein dynamics, e.g., magnetic resonance, fluorescence imaging techniques, mid-infrared spectroscopy and biochemical assays. Spectroscopic analysis, based on the use of terahertz (THz) radiation with frequencies between 0.1 and 15 THz (3–500 cm⁻¹), was underestimated by the biochemical community. In recent years, however, the potential of THz spectroscopy in the analysis of both simple structures, such as polypeptide molecules, and complex structures, such as protein complexes, has been demonstrated. The THz absorption spectrum provides some information on proteins: for small molecules the THz spectrum is dominated by individual modes related to the presence of hydrogen bonds. For peptides, the spectral information concerns their secondary structure, while for complex proteins such as globular proteins and viral glycoproteins, spectra also provide information on collective modes. In this short review, we discuss the results obtained by THz spectroscopy in the protein dynamics investigations. In particular, we will illustrate advantages and applications of THz spectroscopy, pointing out the complementary information it may provide. Full article

The effects of charge carrier trapping on image resolution in multilayer photoconductive imaging detectors was analyzed by developing an analytical model for calculating the modulation transfer function (MTF) of the imaging detectors. The MTF model was developed by considering the charge carrier trapping/recombination in the blocking layer and the distributed trapping in the bulk photoconductor layer of multilayer photoconductive imaging detectors. The relative importance of the bulk and blocking layer trapping, as well as the K-fluorescence reabsorption on the resolution, was also analyzed. The model was applied to amorphous selenium- (a-Se) based multilayer detectors for both chest radiographic and mammographic applications. The theoretical model agreed well with experimental results. The charge carrier trapping/recombination in the blocking layer and K-fluorescence reabsorption mainly controlled the resolution of the a-Se mammographic detectors. In addition to these two effects, the bulk trapping also had a significant effect on the resolution of chest radiographic detectors. The blocking layer thickness had more of a profound effect on the resolution than the amount of trap centers in the blocking layer. The resolution deteriorated drastically with increased blocking layer thickness. Full article

Biological dosimetry is an internationally recognized method for quantifying and estimating radiation dose following suspected or verified excessive exposure to ionising radiation. In severe radiation accidents where a large number of people are potentially affected, it is possible to distinguish irradiated from non-irradiated people in order to initiate appropriate medical care if necessary. In addition to severe incidents caused by technical failure, environmental disasters, military actions, or criminal abuse, there are also radiation accidents in which only one or a few individuals are affected in the frame of occupational or medical exposure. The requirements for biological dosimetry are fundamentally different for these two scenarios. In particular, for large-scale radiation accidents, pre-screening methods are necessary to increase the throughput of samples for a rough first-dose categorization. The rapid development and increasing use of omics methods in research as well as in individual applications provides new opportunities for biological dosimetry. In addition to the discovery and search for new biomarkers, dosimetry assays based on omics technologies are becoming increasingly interesting and hold great potential, especially for large-scale dosimetry. In the following review, the different areas of biological dosimetry, the problems in finding suitable biomarkers, the current status of biomarker research based on omics, the potential applications of assays using omics technologies, and also the limitations for the different areas of biological dosimetry are discussed. Full article

Systematic bio- and databanks are key prerequisites for modern radiation research to investigate radiation response mechanisms in the context of genetic, environmental and lifestyle-associated factors. This report presents the current status of the German Uranium Miners’ Biobank. In 2008, the bio- and databank was established at the Federal Office for Radiation Protection, and the sampling of biological materials from former uranium miners with and without lung cancer was initiated. For this purpose, various biological specimens, such as DNA and RNA, were isolated from blood samples as well as from formalin-fixed paraffin-embedded lung tissue. High-quality biomaterials suitable for OMICs research and the associated data on occupational radiation and dust exposure, and medical and lifestyle data from over 1000 individuals have been stored so far. Various experimental data, e.g., genome-wide SNPs, whole genome transcriptomic and miRNA data, as well as individual chromosomal aberration data from subgroups of biobank samples, are already available upon request for in-depth research on radiation-induced long-term effects, individual radiation susceptibility to lung cancer and radon-induced fingerprints in lung cancer. This biobank is the first systematic uranium miners´ biobank worldwide that is suitable for OMICs research on radiation-exposed workers. It offers the opportunity to link radiation-induced perturbations of biological pathways or processes and putative adverse outcome(s) by OMICs profiling at different biological organization levels. Full article

Rokitansky-Aschoff sinuses (RAS) are a common imaging finding in gallbladder adenomyomatosis (ADM), often presenting as fundal cystic spaces. Intracholecystic papillary neoplasm (ICPN) is a relatively uncommon pre-invasive tumor of the gallbladder epithelium that rarely involves RAS mucosa. We compare two cases that showed similar fundal cystic spaces resembling RAS, in which Magnetic Resonance Diffusion-Weighted Imaging (MR-DWI) was valuable for detecting (or ruling out) an underlying malignant ICPN. Evidence from the literature overall supports the role of MR-DWI for detecting intracholecystic malignant tissue. Full article

It is well known that ionizing radiation can cause damages to cells that interact with it directly. However, many studies have shown that damages also occur in cells that have not experienced direct interaction. This is due to the so-called bystander effect, which is observed when the irradiated cell sends signals that can damage neighboring cells. Due to the complexity of this effect, it is not easy to strictly describe it biophysically, and thus it is also difficult to simulate. This article reviews various approaches to modeling and simulating the bystander effect from the point of view of radiation biophysics. In particular, the last model presented within this article is part of a larger project of modeling the response of a group of cells to ionizing radiation using Monte Carlo methods. The new approach presented here is based on the probability tree, the Poisson distribution of signals and the saturated dose-related probability distribution of the bystander effect’s appearance, which makes the model very broad and universal. Full article

We investigated in this work the radioluminescence properties of a Ce-doped multimode silica-based optical fiber (core diameter of 50 µm) manufactured by the sol–gel technique when exposed to the high-energy X-rays (~600 keV) of the ORIATRON facility of CEA. We demonstrated its potential to monitor in real-time the beam characteristics of this facility that can either operate in a pulsed regime (pulse duration of 4.8 µs, maximum repetition rate of 250 Hz) or in a quasi-continuous mode. The radiation-induced emission (radioluminescence and a minor Cerenkov contribution) linearly grew with the dose rate in the 15–130 mGy(SiO₂)/s range, and the afterglow measured after each pulse was sufficiently limited to allow a clear measurement of pulse trains. A sensor with ~11 cm of sensitive Ce-doped fiber spliced to rad-hard fluorine-doped optical fiber, for the emitted light transport to the photomultiplier tube, exhibited interesting beam monitoring performance, even if the Cerenkov emission in the transport fiber was also considered (~5% of the signal). The beam monitoring potential of this class of optical fiber was demonstrated for such facilities and the possibilities of extending the dose rate range are discussed based on possible architecture choices such as fiber type, length or size. Full article

Children have an increased risk of developing radiation-induced secondary malignancies compared to adults, due to their high radiosensitivity and longer life expectancy. In contrast to the epidemiological evidence, there is only a handful of radiobiology studies which investigate the difference in radiosensitivity between children and adults at a cellular level. In this study, the previous results on the potential age dependency in chromosomal radiosensitivity were validated again by means of the cytokinesis-block micronucleus (CBMN) assay in T-lymphocytes isolated from the umbilical cord and adult peripheral blood of a South African population. The isolated cells were irradiated with ⁶⁰Co γ-rays at doses ranging from 0.5 Gy to 4 Gy. Increased radiosensitivities of 34%, 42%, 29%, 26% and 16% were observed for newborns compared to adults at 0.5, 1, 2, 3 and 4 Gy, respectively. An immunophenotypic evaluation with flow cytometry revealed a significant change in the fraction of naïve (CD45RA⁺) T-lymphocytes in CD4⁺ and CD8⁺ T-lymphocytes with age. Newborns co-expressed an average of 91.05% CD45RA⁺ (range: 80.80–98.40%) of their CD4⁺ cells, while this fraction decreased to an average of 39.08% (range: 12.70–58.90%) for adults. Similar observations were made for CD8⁺ cells. This agrees with previous published results that the observed differences in chromosomal radiosensitivity between newborn and adult T-lymphocytes could potentially be linked to their immunophenotypic profiles. Full article