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We examined how radiation dose per fraction (DPF) and total dose, as represented by biological effective dose (BED), can independently and differentially affect the immunomodulatory capacity of radiation therapy (RT).
The aim of the Low Background Radiation Experiment (LBRE) has been to clarify the effects that low levels of radiation have on biological systems. Experiments started in 2009 and continue each summer. Research for the potential performance of a repository for heat-generating waste in bedded salt. A full-scale prototype heater canister was designed and fabricated in fiscal year 2014 to demonstrate the ability of the prototype canister-heater to operate under realistic conditions for performance and reliability. Testing in the underground started in September 2017 and is ongoing. Currently, there is no power to this experiment due to maintenance in the underground.
Task Group 121 – Effects of ionizing radiation exposure in offspring and next generations – is a task group under the Committee 1 of the International Commission on Radiological Protection (ICRP), approved by the Main Commission on 18th November 2021. The main goals of Task Group 121 are to (1) review and update the scientific literature of relevance to radiation-related effects in the offspring of parent(s) exposed to ionizing radiation in both human and non-human biota; (2) to assess preconceptional and intrauterine effects of radiation exposure and related morbidity and mortality; and, (3) to provide advice about the level of evidence and how to consider these preconceptional and postconceptional effects in the system of radiological protection for humans and non-human biota. The Task Group is reviewing relevant literature since Publication 90 ‘Biological effects after prenatal irradiation (embryo and fetus)’ (2003) and will include radiation-related effects on future generations in humans, animals, and plants. This review will be conducted to account for the health effects on offspring and subsequent generations in the current system of radiological protection. Radiation detriment calculation will also be reviewed. Finally, preliminary recommendations will be made to update the integration of health effects in offspring and next generations in the system of radiological protection. A Workshop, jointly organized by ICRP Task Group 121 and European Radiation Protection Research Platforms MELODI and ALLIANCE was held in Budapest, Hungary, from 31st May to 2nd June 2022. Participants discussed four important topics: (1) hereditary and epigenetic effects due to exposure of the germ cell line (preconceptional exposure), (2) effects arising from exposure of the embryo and fetus (intrauterine exposure), (3) transgenerational effects on biota, and (4) its potential impact on the system of radiological protection. Based on the discussions and presentations during the breakout sessions, newer publications, and gaps on the current scientific literature were identified. For instance, there are some ongoing systematic reviews and radiation epidemiology reviews of intrauterine effects. There are newer methods of Monte Carlo simulation for fetal dosimetry, and advances in radiation genetics, epigenetics, and radiobiology studies. While the current impact of hereditary effects on the global detriment was reported as small, the questions surrounding the effects of radiation exposure on offspring and the next generation are crucial, recurring, and with a major focus on exposed populations. Here, this article summarizes the workshop discussions, presentations, and conclusions of each topic and introduces the special issue of the International Journal of Radiation Biology resulting from the discussions of the meeting.
Irradiation with ultrahigh dose rates (FLASH) has reemerged as a promising radiation therapy approach to effectively lower potential damage burden on normal tissue without sacrificing tumor control. However, the large number of recent FLASH studies have been conducted under vastly different experimental conditions and circumstances (ie, investigated biological endpoint, radiation quality, and environmental oxygen level), with unverified biological mechanisms of action and unexplored interplay effect of the main dependencies. To facilitate radiobiological investigation of FLASH phenomena and assessment of clinical applicability, we present an extension of the mechanistic radiobiological model “UNified and VERSatile bio response Engine” (UNIVERSE).
Vertebral compression fracture is a common complication of spinal stereotactic body radiation therapy. Development of an in vivo model is crucial to fully understand how focal radiation treatment affects vertebral integrity and biology at various dose fractionation regimens. We present a clinically relevant animal model to analyze the effects of localized, high-dose radiation on vertebral microstructure and mechanical integrity. Using this model, we test the hypothesis that fractionation of radiation dosing can reduce focused radiation therapy's harmful effects on the spine.
The respiratory and cardiovascular effects of smoke exposure are well documented from cigarette smoking and particulate matter (PM) associated with air-pollution studies, but epidemiological data also suggests exposure to high levels of woodsmoke correlate with central-nervous-system (CNS) dysfunction, including elevated rates of Alzheimer’s disease (AD) and dementia. Neuro-inflammation is believed to initiate the majority of Alzheimer’s and other neurodegenerative diseases attributed to environmental factors. We investigated whether inhaled PM and specific classes of compounds in wildfire smoke condensate extract (WSE) reach the brain and cause neuro-inflammation that can lead to progressive neurological degeneration, using isotope tracing of labeled particulate matter and major compound classes, biomarkers of blood-brain barrier (BBB) integrity, and biomarkers of neuro-inflammation. This project showed that inhalation exposure to PM and major compound classes present in WSE reached the brain through absorption in the nasal cavity and systemic circulation across the BBB. Twenty-four exposures of WSE to brain endothelial cells that form the main physical barrier of the BBB produced dose-dependent increases in biomarkers of inflammation and decreases in tight junction markers between cells. Intranasal exposure to WSE caused inflammatory disfunction in lung and brain. Biomarkers of inflammation increased and an enzyme inhibiting inflammation decreased. Similar patterns of chemical-induced changes in the lung and brain suggest either: (1) chemicals may act through shared molecular pathways upon entering lung and brain, or (2) that mediators originating in the lung circulate systemically to the brain and drive neuroinflammation. These findings warrant further mechanistic studies to delineate the temporal sequence of events to establish the lung-brain axis.
Compared to low doses of gamma irradiation (γ-IR), high-charge-and-energy (HZE) particle IR may have different biological response thresholds in cardiac tissue at lower doses, and these effects may be IR type and dose dependent. Three- to four-month-old female CB6F1/Hsd mice were exposed once to one of four different doses of the following types of radiation: γ-IR 137Cs (40-160 cGy, 0.662 MeV), 14Si-IR (4-32 cGy, 260 MeV/n), or 22Ti-IR (3-26 cGy, 1 GeV/n). At 16 months post-exposure, animals were sacrificed and hearts were harvested and archived as part of the NASA Space Radiation Tissue Sharing Forum. These heart tissue samples were used in our study for RNA isolation and microarray hybridization. Functional annotation of twofold up/down differentially expressed genes (DEGs) and bioinformatics analyses revealed the following: (i) there were no clear lower IR thresholds for HZE- or γ-IR; (ii) there were 12 common DEGs across all 3 IR types; (iii) these 12 overlapping genes predicted various degrees of cardiovascular, pulmonary, and metabolic diseases, cancer, and aging; and (iv) these 12 genes revealed an exclusive non-linear DEG pattern in 14Si- and 22Ti-IR-exposed hearts, whereas two-thirds of γ-IR-exposed hearts revealed a linear pattern of DEGs. Thus, our study may provide experimental evidence of excess relative risk (ERR) quantification of low/very low doses of full-body space-type IR-associated degenerative disease development.
Red blood cell distribution width (RDW), which generally increases with age, is a risk marker for morbidity and mortality in various diseases. We investigated the association between elevated RDW and prior radiation exposure by examining longitudinal RDW changes in 4204 atomic-bomb survivors over 15 years. A positive association was found between RDW and radiation dose, wherein RDW increased by 0·18%/Gy. This radiation-associated effect increased as the participants aged. Elevated RDW was also associated with higher all-cause mortality. The biological mechanisms underlying these observed associations merit further investigation.
The structural integrity of the concrete biological shield (CBS) in light water reactors (LWRs) exposed to long-term radiation raises the question of the effects of fast-neutron and gamma irradiation on the bond properties of embedded carbon-steel reinforcement in concrete, which is critical to the transfer of in-service and accidental loads. The design and execution of a first-of-a-kind irradiation experiment conducted in the LVR-15 test reactor (Czech Republic) are presented along with preliminary post-irradiation examination and testing results. Preliminary analysis shows that the fast neutron flux affects the radiation-induced volumetric of concrete aggregate, that the gamma irradiation induces shrinkage of the chemically bonded water in cementitious hydrates and that the bond strength of steel in concrete at the tested irradiation conditions decreases moderately.
Definitive, nonsurgical management of gynecologic malignancies involves external beam radiation therapy (EBRT) and/or brachytherapy (BT). Summation of the cumulative dose is critical to assess the total biologic effective dose to targets and organs at risk. Cumulative dose calculation from EBRT and BT can be performed with or without image registration (IR) and biologic dose summation. Among these dose summation strategies, linear addition of dose-volume histogram (DVH) parameters without IR is the global standard for composite dose reporting. This approach stems from an era without image guidance and simple external beam and brachytherapy treatment approaches. With technological advances, EBRT and high-dose-rate BT have evolved to allow for volume-based treatment planning and delivery. Modern conformal therapeutic radiation involves volumetric or intensity modulated EBRT, capable of simultaneously treating multiple targets at different specified dose levels. Therefore, given the complexity of modern radiation treatment, the linear addition of DVH parameters from EBRT and high-dose-rate BT is challenging to represent the combined dose distribution. Deformable image registration (DIR) between EBRT and image guided brachytherapy (IGBT) data sets may provide a more nuanced calculation of multimodal dose accumulation. However, DIR is still nascent in this regard, and needs further development for accuracy and efficiency for clinical use. Biologic dose summation can combine physical dose maps from EBRT and each IGBT fraction, thereby generating a composite DVH from the biologic effective dose. However, accurate radiobiologic parameters are tissue-dependent and not well characterized. A combination of voxel-based DIR and biologic weighted dose maps may be the best approximation of dose accumulation but remains invalidated. The purpose of this report is to review dose summation strategies for EBRT and BT, including conventional equivalent dose in 2-Gy fractions dose summation without image registration, physical dose summation using 3-dimensional rigid IR and DIR, and biologic dose summation. We also provide general clinical workflows for IGBT with a focus on cervical cancer.
Deuterium (D) seems to play an important role in biology and is thought to be a missing piece in understanding cancer and radiation resistance. D is found in natural water at a concentration of ~150 parts per million (ppm), while D concentrations above 150 ppm are known to produce toxic effects in many organisms. There is evidence to suggest D levels significantly less than 150 ppm can cause delays in cell progression through the normal mitotic cell cycle. Some have theorized that the deuterium: hydrogen ratio (D:H) in cells may impact radiation resistance. Therefore, evaluating the role of D in human cells should lead to a better understanding of cell cycle progression and radiation resistance. To date, little has been revealed on the time-dependent effects of deuterium-depleted water (DDW – less than 150 ppm) on normal and cancer human cells or how the reduction of cell proliferation is associated with cell cycle regulation and consequence on gene expression profiles. Our studies will help further the mission of the Department of Energy to enhance the understanding of deuterium in fundamental biology by studying the cell cycle as a function of D concentration.
Deuterium (D) seems to play an important role in biology and is thought to be a missing piece in understanding cancer and radiation resistance. D is found in natural water at a concentration of ~150 parts per million (ppm), while D concentrations above 150 ppm are known to produce toxic effects in many organisms. There is evidence to suggest D levels significantly less than 150 ppm can cause delays in cell progression through the normal mitotic cell cycle. Some have theorized that the deuterium: hydrogen ratio (D:H) in cells may impact radiation resistance. Therefore, evaluating the role of D in human cells should lead to a better understanding of cell cycle progression and radiation resistance. To date, little has been revealed on the time-dependent effects of deuterium-depleted water (DDW – less than 150 ppm) on normal and cancer human cells or how the reduction of cell proliferation is associated with cell cycle regulation and consequence on gene expression profiles. Our studies will help further the mission of the Department of Energy to enhance the understanding of deuterium in fundamental biology by studying the cell cycle as a function of D concentration.
Concrete is massively used in the construction of critical safety-related components in nuclear power plants. Among those, the concrete biological shield is exposed to high levels of neutron and gamma irradiation exiting the reactor pressure vessel. This article provides a comprehensive overview of the state-of-the-art knowledge on irradiated concrete. First, the fundamental irradiation-induced degradation mechanisms occurring at the level of the concrete constituents such as rock-forming minerals and hydrated cementitious phases are examined. The critical role of the mineralogical and chemical composition regarding concrete resistance against radiation effects such as amorphization, irradiation-induced expansion and radiolytic gas release are detailed. Second, the interactions between the varied irradiated phases are comprehensively analyzed and put in perspectives with the effects of prolonged irradiation on the structural properties of concrete aggregates, cement paste, and concretes. Finally, the significance of irradiation for the long-term operation of nuclear power plants is discussed in the light of the most recent knowledge and its limitations.
In September 2020, the Laboratory’s Chemical Microscopy Facility tripled in size, expanding to 1,000 square feet. Located at TA-46, Building158, this facility houses a unique Laboratory resource. Operated by the Physical Chemistry and Applied Spectroscopy (C-PCS) group, this facility was established to renew the Laboratory’s rich history in radiobiology. The facility combines biological research capabilities with isotope production, as well as radioanalytical and chemical infrastructure. This facility provides space for Biosafety Level 2 (BSL-2) research, with alpha-emitting and other radionuclides of interest associated with biological systems. Equipped with a Class ll/A2 biological safety cabinet, a radiological fume hood and a host of other analytical equipment, this facility serves an effective resource to evaluate the efficacy of targeted alpha therapeutics, as well as the deleterious effects of radiological materials on living organisms. The facility receives funding through LDRD- 20180005DR, “Establishing a Radiotherapeutic Capability to Counter Biothreats,” and the BES Heavy Element Chemistry Program at the Laboratory.
We are committed to act as stewards of our environment to achieve our mission in accordance with all applicable environmental requirements. We set continual improvement objectives and targets, measure and document our progress, and share our results with our workforce, sponsors, and public. We reduce our environmental risk through legacy cleanup, pollution prevention, and long-term sustainability programs.
Commercial-scale marine renewable energy (MRE) developments continue to progress slowly, in part because of complicated consenting/permitting (hereafter consenting) processes that invoke the precautionary principle within environmental legislative frameworks. This can lead to broad, poorly scoped environmental assessments, lengthy and expensive environmental data collection requirements, and extended consenting timelines. Much of this delay is associated with uncertainty about the potential effects of MRE on marine animals and habitats. https://tethys.pnnl.gov/publications/state-of-the-science-2020-chapter-13-risk-retirement
Most marine renewable energy (MRE) devices must be attached to the seafloor in some way, either through gravity foundations, pilings, or anchors, and with mooring lines, transmission cables, and devices themselves in the water column. Physical changes in benthic and pelagic habitats have the potential to alter species occurrence or abundance at a localized scale, lead to some level of habitat loss, provide opportunities for colonization by non-native species, alter patterns of ecological succession, modify ecosystem functioning, and affect behavioral responses of marine organisms. The transformation of the seafloor and/or water column habitat to new hard substratum because of the presence of the MRE devices may also lead to artificial reef effects or changes in animal behavior. While there is no indication that MRE devices affect marine habitats differently than other structures currently and historically placed in the ocean, regulators and stakeholders may continue to have concerns. https://tethys.pnnl.gov/publications/state-of-the-science-2020-chapter-6-habitat-changes
This pilot study suggests relatively short (median 12 days long) low-Earth orbit (LEO) spaceflight induces changes in circulating plasma small extracellular vesicle (sEV) microRNA expression. Normalization of small RNA sequencing (sRNAseq) data and quantitative polymerase chain reaction (qPCR) validation confirmed miR-4732-3p is significantly upregulated up to 3 days post-landing, and enrichment analysis suggests this miRNA is expressed in various central nervous system tissues and hematopoietic cells and may be linked to different organ disorders.