Microfluidic measurement of intracellular mRNA with a molecular beacon probe towards point-of-care radiation triage.

In large-scale radiation exposure events, the ability to triage potential victims by the received radiation dosage is crucial. This can be evaluated by radiation-induced biological changes. Radiation-responsive mRNA is a class of biomarkers that has been explored for dose-dependency with methods such as RT-qPCR.

Applicability of Gene Expression in Saliva as an Alternative to Blood for Biodosimetry and Prediction of Radiation-induced Health Effects.

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.

RENEB Inter-Laboratory Comparison 2021: Inter-Assay Comparison of Eight Dosimetry Assays.

Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results.

RENEB Inter-Laboratory Comparison 2021: The Gene Expression Assay.

Early and high-throughput individual dose estimates are essential following large-scale radiation exposure events. In the context of the Running the European Network for Biodosimetry and Physical Dosimetry (RENEB) 2021 exercise, gene expression assays were conducted and their corresponding performance for dose-assessment is presented in this publication. Three blinded, coded whole blood samples from healthy donors were exposed to 0, 1.

Longitudinal multi-omic changes in the transcriptome and proteome of peripheral blood cells after a 4 Gy total body radiation dose to Rhesus macaques.

Background: Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days and at the cytogenetic level out to 56 days after exposure. We combine the global transcriptomic and proteomic responses in peripheral whole blood to assess the impact of acute TBI exposure at extended times post irradiation.

Cross-platform validation of a mouse blood gene signature for quantitative reconstruction of radiation dose.

In the search for biological markers after a large-scale exposure of the human population to radiation, gene expression is a sensitive endpoint easily translatable to in-field high throughput applications. Primarily, the ex-vivo irradiated healthy human blood model has been used to generate available gene expression datasets. This model has limitations i.

Biofluid Metabolomics and Lipidomics of Mice Exposed to External Very High-Dose Rate Radiation.

High-throughput biodosimetry methods to determine exposure to ionizing radiation (IR) that can also be easily scaled to multiple testing sites in emergency situations are needed in the event of malicious attacks or nuclear accidents that may involve a substantial number of civilians. In the event of an improvised nuclear device (IND), a complex IR exposure will have a very high-dose rate (VHDR) component from an initial blast. We have previously addressed low-dose rate (LDR, ≤1 Gy/day) exposures from internal emitters on biofluid small molecule signatures, but further research on the VHDR component of the initial blast is required.

Examining potential confounding factors in gene expression analysis of human saliva and identifying potential housekeeping genes.

Isolation of RNA from whole saliva, a non-invasive and easily accessible biofluid that is an attractive alternative to blood for high-throughput biodosimetry of radiological/nuclear victims might be of clinical significance for prediction and diagnosis of disease. In a previous analysis of 12 human samples we identified two challenges to measuring gene expression from total RNA: (1) the fraction of human RNA in whole saliva was low and (2) the bacterial contamination was overwhelming. To overcome these challenges, we performed selective cDNA synthesis for human RNA species only by employing poly(A)+-tail primers followed by qRT-PCR.

Biofluid Metabolomics of Mice Exposed to External Low-Dose Rate Radiation in a Novel Irradiation System, the Variable Dose-Rate External Cs Irradiator.

An important component of ionizing radiation (IR) exposure after a radiological incident may include low-dose rate (LDR) exposures either externally or internally, such as from Cs deposition. In this study, a novel irradiation system, VAriable Dose-rate External Cs irradiatoR (VADER), was used to expose male and female mice to a variable LDR irradiation over a 30 d time span to simulate fall-out-type exposures in addition to biofluid collection from a reference dose rate (0.8 Gy/min).

Inter-laboratory comparison of gene expression biodosimetry for protracted radiation exposures as part of the RENEB and EURADOS WG10 2019 exercise.

Large-scale radiation emergency scenarios involving protracted low dose rate radiation exposure (e.g. a hidden radioactive source in a train) necessitate the development of high throughput methods for providing rapid individual dose estimates.

VADER: a variable dose-rate external Cs irradiator for internal emitter and low dose rate studies.

In the long term, Cs is probably the most biologically important agent released in many accidental (or malicious) radiation disasters. It can enter the food chain, and be consumed, or, if present in the environment (e.g.

Dose and Dose-Rate Effects in a Mouse Model of Internal Exposure from 137Cs. Part 2: Integration of Gamma-H2AX and Gene Expression Biomarkers for Retrospective Radiation Biodosimetry.

Inhalation and ingestion of 137Cs and other long-lived radionuclides can occur after large-scale accidental or malicious radioactive contamination incidents, resulting in a complex temporal pattern of radiation dose/dose rate, influenced by radionuclide pharmacokinetics and chemical properties. High-throughput radiation biodosimetry techniques for such internal exposure are needed to assess potential risks of short-term toxicity and delayed effects (e.g.

Dose and Dose-Rate Effects in a Mouse Model of Internal Exposure to 137Cs. Part 1: Global Transcriptomic Responses in Blood.

Internal contamination by radionuclides may constitute a major source of exposure and biological damage after radiation accidents and potentially in a dirty bomb or improvised nuclear device scenario. We injected male C57BL/6 mice with radiolabeled cesium chloride solution (137CsCl) to evaluate the biological effects of varying cumulative doses and dose rates in a two-week study. Injection activities of 137CsCl were 5.

Discordant gene responses to radiation in humans and mice and the role of hematopoietically humanized mice in the search for radiation biomarkers.

The mouse (Mus musculus) is an extensively used model of human disease and responses to stresses such as ionizing radiation. As part of our work developing gene expression biomarkers of radiation exposure, dose, and injury, we have found many genes are either up-regulated (e.g.

New Approaches for Quantitative Reconstruction of Radiation Dose in Human Blood Cells.

In the event of a nuclear attack or large-scale radiation event, there would be an urgent need for assessing the dose to which hundreds or thousands of individuals were exposed. Biodosimetry approaches are being developed to address this need, including transcriptomics. Studies have identified many genes with potential for biodosimetry, but, to date most have focused on classification of samples by exposure levels, rather than dose reconstruction.

Effect of dose and dose rate on temporal γ-H2AX kinetics in mouse blood and spleen mononuclear cells in vivo following Cesium-137 administration.

Background: Cesium-137 (Cs) is one of the major and most clinically relevant radionuclides of concern in a radiological dispersal device, "dirty bomb" scenario as well as in nuclear accidents and detonations. In this exposure scenario, a significant amount of soluble radionuclide(s) may be dispersed into the atmosphere as a component of fallout. The objectives of the present study were to investigate the effect of protracted Cs radionuclide exposures on DNA damage in mouse blood and spleen mononuclear cells (MNCs) in vivo using the γ-H2AX biomarker, and to develop a mathematical formalism for these processes.

Global Gene Expression Response in Mouse Models of DNA Repair Deficiency after Gamma Irradiation.

In the event of an improvised nuclear device or "dirty bomb" in a highly populated area, potentially hundreds of thousands of people will require screening to ensure that exposed individuals receive appropriate treatment. For this reason, there is a need to develop tools for high-throughput radiation biodosimetry. Gene expression represents an emerging approach to biodosimetry and could potentially provide an estimate of both absorbed dose and individual radiation-induced injury.