Effect of changing the radiation dose range on the in vitro cytogenetic dose response to gamma-rays.

Purpose: To examine the distortion of the linear quadratic (LQ) model of in vitro cytogenetic dose response over an extended range of γ-ray doses by analyzing the available literature data, and to establish the dose ranges, in which the LQ dose response curve (DRC) can be most accurately fitted for biological dosimetry.

Materials And Methods: Data on yields of dicentrics (Dic) or dicentrics plus centric rings (Dic + CR) induced in vitro in human lymphocytes by acute γ-rays were extracted from 108 open sources. The overall dose response dataset in the dose range up to 50 Gy was fitted to a fractional-rational (FR) model, which included a 'basic' LQ function in the numerator, and a reduction factor dependent on the square of the dose in the denominator.

Transcriptional Dynamics of DNA Damage Responsive Genes in Circulating Leukocytes during Radiotherapy.

External beam radiation therapy leads to cellular activation of the DNA damage response (DDR). DNA double-strand breaks (DSBs) activate the ATM/CHEK2/p53 pathway, inducing the transcription of stress genes. The dynamic nature of this transcriptional response has not been directly observed in vivo in humans.

Clinical Applications of Biological Dosimetry in Patients Exposed to Low Dose Radiation Due to Radiological, Imaging or Nuclear Medicine Procedures.

Radiation dosimetric biomarkers have found applications beyond radiation protection area and now are actively introduced into clinical practice. Cytogenetic assays appeared to be a valuable tool for individualized quantifying radiation effects in patients, with high capability for assessing genotoxicity of various medical exposure modalities and providing meaningful radiation dose estimates for prognoses of radiation-related cancer risk. This review summarized current data on the use of biological dosimetry methods in patients undergoing various medical irradiations to low doses.

Prognostic assessment of the zone of occurrence of radiation combined injuries within a nuclear blast area.

Background: A detonation of nuclear weapon (NW) is considered as one of the most devastating radiological scenarios in the list of modern global threats. An essential proportion of victims in a mass casualty radiation event may require an immediate medical care due to radiation combined injuries (RCI). Surprisingly, there is a lack of clear guidance for quantitative prognosis of the spatial distribution of expected RCI casesin a given nuclear explosion scenario.

Prediction of the Acute or Late Radiation Toxicity Effects in Radiotherapy Patients Using Ex Vivo Induced Biodosimetric Markers: A Review.

A search for effective methods for the assessment of patients' individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction of individual clinical radiosensitivity (normal tissue toxicity, NTT) in cells of cancer patients undergoing therapeutic irradiation. In approximately 50% of the relevant reports, selected for the analysis in peer-reviewed international journals, the average ex vivo induced yield of these biodosimetric markers was higher in patients with severe reactions than in patients with a lower grade of NTT.

Radiation Exposure Biomarkers in the Practice of Medical Radiology: Cooperative Research and the Role of the International Atomic Energy Agency (IAEA) Biodosimetry/Radiobiology Laboratory.

The strategy toward personalized medicine in radiation oncology, nuclear medicine, and diagnostic and interventional radiology demands a specific set of assays for individualized estimation of radiation load for safety concerns and prognosis of normal tissue reactions caused by ionizing radiation. Apparently, it seems reasonable to use validated radiation dosimetric biomarkers for these purposes. However, a number of gaps in knowledge and methodological limitations still have to be resolved until dosimetric biomarkers will start to play a valuable role in clinical practice beyond radiation protection and radiation medicine.

The assessment of radiation hazardous areas considering the spectral analysis of the neutron component of a tactical neutron bomb detonation.

This study provides an improved background for the operational assessment of the radiation hazardous areas with induced radioactivity, based on the analysis of spectral characteristics of the neutron component of the penetrating radiation. The interrelationships between the nuclear munitions explosion parameters, environmental conditions and dosimetric characteristics of the secondary gamma-ray emission from the activated soil are analyzed. The interrelationships of these parameters are used in the methodology of the assessment of the dosimetric characteristics of the radiation hazardous areas.

CLINICAL APPLICATIONS OF BIOMARKERS OF RADIATION EXPOSURE: LIMITATIONS AND POSSIBLE SOLUTIONS THROUGH COORDINATED RESEARCH.

Dosimetric biomarkers have been effectively and intensively used for a long time in the area of radiation protection. In contrast to that, no robust standards or widely accepted protocols for application of these end-points in radiotherapy, diagnostic and interventional radiology and nuclear medicine exist to date. The International Atomic Energy Agency (IAEA) organized the review of the available data on the possibilities of the use of dosimetric biomarkers in medical irradiation scenarios.

Optimizing the Microscopy Time Schedule for Chromosomal Dosimetry of High-dose and Partial-body Irradiations.

The methodology of cytogenetic triage can be improved by optimizing a schedule of microscopy for different exposure scenarios. Chromosome aberrations were quantified by microscopy in human blood lymphocytes irradiated to ~2, 4, and 12 Gy acute Co γ-rays mixed with the unirradiated blood simulating 10%, 50%, 90%, and 100% exposure and in along with a sample from a homogeneous exposure to ~20 Gy. Biodosimetry workload was statistically modeled assuming that 0.

A new Bayesian model applied to cytogenetic partial body irradiation estimation.

A new zero-inflated Poisson model is introduced for the estimation of partial body irradiation dose and fraction of body irradiated. The Bayes factors are introduced as tools to help determine whether a data set of chromosomal aberrations obtained from a blood sample reflects partial or whole body irradiation. Two examples of simulated cytogenetic radiation exposure data are presented to demonstrate the usefulness of this methodology in cytogenetic biological dosimetry.

Review of Bayesian statistical analysis methods for cytogenetic radiation biodosimetry, with a practical example.

Classical methods of assessing the uncertainty associated with radiation doses estimated using cytogenetic techniques are now extremely well defined. However, several authors have suggested that a Bayesian approach to uncertainty estimation may be more suitable for cytogenetic data, which are inherently stochastic in nature. The Bayesian analysis framework focuses on identification of probability distributions (for yield of aberrations or estimated dose), which also means that uncertainty is an intrinsic part of the analysis, rather than an 'afterthought'.

CytoBayesJ: software tools for Bayesian analysis of cytogenetic radiation dosimetry data.

A number of authors have suggested that a Bayesian approach may be most appropriate for analysis of cytogenetic radiation dosimetry data. In the Bayesian framework, probability of an event is described in terms of previous expectations and uncertainty. Previously existing, or prior, information is used in combination with experimental results to infer probabilities or the likelihood that a hypothesis is true.

A comparison of six statistical distributions for analysis of chromosome aberration data for radiation biodosimetry.

The Poisson distribution is the most widely recognised and commonly used distribution for cytogenetic radiation biodosimetry. However, it is recognised that, due to the complexity of radiation exposure cases, other distributions may be more properly applied. Here, the Poisson, gamma, negative binomial, beta, Neyman type-A and Hermite distributions are compared in terms of their applicability to 'real-life' radiation exposure situations.

Cytogenetic dose-response in vitro for biological dosimetry after exposure to high doses of gamma-rays.

The dose response for dicentrics plus centric rings and total unstable chromosome-type aberrations was studied in the first mitoses of cultured human peripheral blood lymphocytes irradiated in vitro to doses of ∼2, 4, 6, 8, 10, 16 and 20 Gy of acute (60)Со gamma-rays. A dose-dependent increase of aberration yield was accompanied by a tendency to the underdispersion of dicentrics and centric rings among cells distributions compared with Poisson statistics at doses ≥6 Gy. The formal fitting of the data to a linear-quadratic model resulted in an equation with the linear and quadratic coefficients ranged 0.

Bystander apoptosis in human cells mediated by irradiated blood plasma.

Following exposure to high doses of ionizing radiation, due to an accident or during radiotherapy, bystander signalling poses a potential hazard to unirradiated cells and tissues. This process can be mediated by factors circulating in blood plasma. Thus, we assessed the ability of plasma taken from in vitro irradiated human blood to produce a direct cytotoxic effect, by inducing apoptosis in primary human peripheral blood mononuclear cells (PBM), which mainly comprised G(0)-stage lymphocytes.

Limitations associated with analysis of cytogenetic data for biological dosimetry.

The scientific literature concerning cytogenetic biodosimetry has been reviewed to identify the range of scenarios of radiation exposure where biodosimetry has been carried out. Limitations in the existing standardized statistical methodology have been identified and categorized, and the reasons for these limitations have been explored. Statistical problems generally occur due to either low numbers of aberrations leading to large uncertainties or deviations in aberration-per-cell distributions leading to over- or under-dispersion with respect to the Poisson model.

Delayed chromosomal instability in lymphocytes of cancer patients after radiotherapy.

Purpose: To assess possible delayed chromosomal instability (DCI) expressed as elevated chromatid breakage in cells containing previously formed chromosome type aberrations in cultured blood lymphocytes of cancer patients after radiotherapy (RT).

Materials And Methods: Twenty patients treated for uterine cancer with external Co(60) RT, without chemotherapy, were selected. Blood was taken before, 1-2 days after RT and one year later.