Radiation Research

Mathematical models, which describe effects of partial-body, two- and multiple-pulse irradiation at high total doses D and at average dose rates N from FLASH to conventional rates on the level of surviving blood lymphocytes in humans and mice, have been developed originating in the previously proposed approach. These models predict that levels of surviving blood lymphocytes in humans and mice increase with increasing the dose rate from N = D / TR (TR is the time of the blood flowing into or out of the irradiated segment of the blood circulatory system) to FLASH rates and approach an upper limiting level equal to (1- vR), where vR is the fraction of blood volume in the irradiated segment of the blood circulatory system...

There have been a number of reported human exposures to high dose radiation, resulting from accidents at nuclear power plants (e.g., Chernobyl), atomic bombings (Hiroshima and Nagasaki), and mishaps in industrial and medical settings. If absorbed radiation doses are high enough, evolution of acute radiation syndromes (ARS) will likely impact both the bone marrow as well as the gastrointestinal (GI) tract. Damage incurred in the latter can lead to nutrient malabsorption, dehydration, electrolyte imbalance, altered microbiome and metabolites, and impaired barrier function, which can lead to septicemia and death...

A mathematical model developed by Cucinotta and Smirnova is extended to describe effects of continuous, partial-body irradiation at high doses D and at dose N rates from FLASH to conventional rates on the level of surviving blood lymphocytes in humans and small laboratory animals (mice). Specifically, whereas the applicability of the model is limited to the exposure times shorter than a single cardiac cycle T0, the extended model is capable of describing such effects for the aforementioned and longer exposure times...

This review focuses on early discoveries that contributed to our understanding and the scope of transcriptional responses after radiation damage. Before the development of modern approaches to assess overall global transcriptomic responses, the idea that mammalian cells could respond to DNA-damaging agents in a manner analogous to bacteria was not generally accepted. To investigate this possibility, the development of technology to identify differentially expressed low-abundance transcripts substantially facilitated our appreciation that DNA damaging agents like UV radiation and subsequently ionizing radiation did in fact produce robust transcriptional responses...

Radiation enteritis is a common complication of abdominal and pelvic radiotherapy. Several previous studies showed that fecal microbiota transplantation (FMT) could alleviate radiation enteritis. In this study, we investigated the efficacy of FMT in alleviating radiation enteritis and explored the mechanisms by multi-omics approaches. Briefly, C57BL/6J mice were subjected to 9 Gy irradiation to the localized abdominal field, and randomized received FMT from healthy donor mice or saline. H&E staining of harvested small intestine showed FMT decreased epithelial injury...

Micronuclei, detected through the cytokinesis-block micronucleus assay, are valuable indicators of ionizing radiation exposure, especially in short-term lymphocyte cultures. The peripheral human blood lymphocyte assay is recognized as a prime candidate for automated biodosimetry. In a prior project at the Columbia University Center for Radiological Research, we automated this assay using the 96-well ANSI/SLAS microplate standard format and relied on established biotech robotic systems named Rapid Automated Biodosimetry Tool (RABiT)...

In times of war, radiological/nuclear emergency scenarios have become a reemphasized threat. However, there are challenges in transferring whole-blood samples to laboratories for specialized diagnostics using RNA. This project aims to miniaturize the process of unwieldy conventional RNA extraction with its stationed technical equipment using a microfluidic-based slide (MBS) for point-of-care diagnostics. The MBS is thought to be a preliminary step toward the development of a so-called lab-on-a-chip microfluidic device...

As the great majority of gene expression (GE) biodosimetry studies have been performed using blood as the preferred source of tissue, searching for simple and less-invasive sampling methods is important when considering biodosimetry approaches. Knowing that whole saliva contains an ultrafiltrate of blood and white blood cells, it is expected that the findings in blood can also be found in saliva. This human in vivo study aims to examine radiation-induced GE changes in saliva for biodosimetry purposes and to predict radiation-induced disease, which is yet poorly characterized...

In gene expression (GE) studies, housekeeping genes (HKGs) are required for normalization purposes. In large-scale inter-laboratory comparison studies, significant differences in dose estimates are reported and divergent HKGs are employed by the teams. Among them, the 18S rRNA HKG is known for its robustness. However, the high abundance of 18S rRNA copy numbers requires dilution, which is time-consuming and a possible source of errors. This study was conducted to identify the most promising HKGs showing the least radiation-induced GE variance after radiation exposure...

Despite the large variety of high-voltage semiconductor components for medium and high voltage switching and pulse-forming applications as well as for high-power high-frequency generation, the use of vacuum electron tubes still prevails to a considerable degree. Due to the common design incorporating a high energy electron beam which finally is dumped into an anode or a resonator cavity, these tubes are also considered as sources of X rays produced as bremsstrahlung and characteristic radiation, which are referred to as parasitic X rays...

Increased radiological and nuclear threats require preparedness. Our earlier work identified a set of four genes (DDB2, FDXR, POU2AF1 and WNT3), which predicts severity of the hematological acute radiation syndrome (H-ARS) within the first three days postirradiation In this study of 41 Rhesus macaques (Macaca mulatta, 27 males, 14 females) irradiated with 5.8-7.2 Gy (LD29-50/60), including some treated with gamma-tocotrienol (GT3, a radiation countermeasure) we independently validated these genes as predictors in both sexes and examined them after three days...

We present an extension of the Local Effect Model (LEM) to include time-dose relationships for predicting effects of protracted and split-dose ion irradiation at arbitrary LET. With this kinetic extension, the spatial and temporal induction and processing of DNA double strand breaks (DSB) in cellular nuclei can be simulated for a wide range of ion radiation qualities, doses and dose rates. The key concept of the extension is based on the joint spatial and temporal coexistence of initial DSB, leading to the formation of clustered DNA damage on the µm scale (as defined e...

The U.S. Government is committed to maintaining a robust research program that supports a portfolio of scientific experts who are investigating the biological effects of radiation exposure. On August 17 and 18, 2023, the Radiation and Nuclear Countermeasures Program, within the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), partnered with the National Cancer Institute, NIH, the National Aeronautics and Space Administration, and the Radiation Injury Treatment Network to convene a workshop titled, Advanced Technologies in Radiation Research (ATRR), which focused on the use of advanced technologies under development or in current use to accelerate radiation research...

We report the dose rate dependence of radiation chemical yields (G value) of water radiolysis products under clinical energy protons (230 MeV) to understand mechanisms of the FLASH radiotherapy performed at ultra-high dose rate (>40 Gy/s). The G value of 7-hydoroxy-coumarin-3-carboxylic acid (7OH-C3CA) produced by reactions of coumarin-3-carboxylic acid (C3CA) with OH radicals and oxygen is evaluated by fluorescence method. Also, those of hydrated electrons and hydrogen peroxide are derived by absorption method using Saltzman and Ghomley techniques, respectively...

High-LET-type cell survival curves have been observed in cells that were allowed to incorporate 125I-UdR into their DNA. Incorporation of tritiated thymidine into the DNA of cells has also been shown to result in an increase in relative biological effectiveness in cell survival experiments, but the increase is smaller than observed after incorporation of 125I-UdR. These findings are explained in the literature by the overall complexity of the induced DNA damage resulting from energies of the ejected electron(s) during the decay of 3H and 125I...

The Radiation and Nuclear Countermeasures Program (RNCP) at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) was established to facilitate the development of medical countermeasures (MCMs) and diagnostic approaches for use in a radiation public health emergency. Approvals for MCMs can be very challenging but are made possible under the United States Food and Drug Administration (FDA) Animal Rule, which is designed to enable licensure of drugs or biologics when clinical efficacy studies are unethical or unfeasible...

With the current volatile geopolitical climate, the threat of nuclear assault is high. Exposure to ionizing radiation from either nuclear incidents or radiological accidents often lead to major harmful consequences to human health. Depending on the absorbed dose, the symptoms of the acute radiation syndrome and delayed effects of acute radiation exposure (DEARE) can appear within hours, weeks to months. The lung is a relatively radiosensitive organ with manifestation of radiation pneumonitis as an acute effect, followed by apparent fibrosis in weeks or even months...

Radiation-induced intestinal damage (RIID) is a common side effect of radiotherapy in patients with abdominopelvic malignancies. Gap junctions are special structures consisting of connexins (Cxs). This study aimed to investigate the expression and role of connexins in RIID and underlying mechanism. In this study, a calcein-AM fluorescence probe was used to detect changes in gap junctional intercellular communication in intestinal epithelial IEC-6 cells. Our results show that gap junctional intercellular communication of IEC-6 cells was reduced at 6, 12, 24, and 48 h after irradiation, with the most pronounced effect at 24 h...

The search for medical treatments to prevent radiation-induced damage to gastrointestinal tissue is crucial as such injuries can be fatal. This study aimed to investigate the effects of apigenin (AP) on the gut microbiome of irradiated mice, as it is a promising radiation countermeasure. Male C57BL/6J mice were divided into four groups, with six mice in each group. Two groups were given food with apigenin (20 mg/kg body weight or AP 20) before and after exposure to 0 or 50 cGy of silicon (28Si) ions, while another two groups of mice received regular diet without apigenin (0 mg/kg body weight or AP 0) before and after irradiation...

In the current geopolitical climate there is an unmet need to identify and develop prophylactic radiation countermeasures, particularly to ensure the well-being of warfighters and first responders that may be required to perform on radiation-contaminated fields for operational or rescue missions. Currently, no countermeasures have been approved by the U.S. FDA for prophylactic administration. Here we report on the efficacious nature of FSL-1 (toll-like receptor 2/6 agonist) and the protection from acute radiation syndrome (ARS) in a murine total-body irradiation (TBI) model...