RENEB/EURADOS field exercise 2019: robust dose estimation under outdoor conditions based on the dicentric chromosome assay.

Purpose: Biological and/or physical assays for retrospective dosimetry are valuable tools to recover the exposure situation and to aid medical decision making. To further validate and improve such biological and physical assays, in 2019, EURADOS Working Group 10 and RENEB performed a field exercise in Lund, Sweden, to simulate various real-life exposure scenarios.

Materials And Methods: For the dicentric chromosome assay (DCA), blood tubes were located at anthropomorphic phantoms positioned in different geometries and were irradiated with a 1.

RENEB Inter-Laboratory comparison 2017: limits and pitfalls of ILCs.

Purpose: In case of a mass-casualty radiological event, there would be a need for networking to overcome surge limitations and to quickly obtain homogeneous results (reported aberration frequencies or estimated doses) among biodosimetry laboratories. These results must be consistent within such network. Inter-laboratory comparisons (ILCs) are widely accepted to achieve this homogeneity.

Micronucleus Assay: The State of Art, and Future Directions.

During almost 40 years of use, the micronucleus assay (MN) has become one of the most popular methods to assess genotoxicity of different chemical and physical factors, including ionizing radiation-induced DNA damage. In this minireview, we focus on the position of MN among the other genotoxicity tests, its usefulness in different applications and visibility by international organizations, such as International Atomic Energy Agency, Organization for Economic Co-operation and Development and International Organization for Standardization. In addition, the mechanism of micronuclei formation is discussed.

Cytotoxicity and antigenotoxicity evaluation of acetylshikonin and shikonin.

Shikonin (SH) is used as a red pigment for food coloring and cosmetics, and has cytotoxic activity towards cancer cells. However, due to strong toxicity SH has limited potential as an anticancer drug. Acetylshikonin (ASH) is one of the SH derivatives with promising anticancer potential.

Hypothermia modulates the DNA damage response to ionizing radiation in human peripheral blood lymphocytes.

Purpose: Low temperature at exposure has been shown to act in a radioprotective manner at the level of cytogenetic damage. It was suggested to be due to an effective transformation of DNA damage to chromosomal damage at low temperature. The purpose of the study was to analyze the kinetics of aberration formation during the first hours after exposing human peripheral blood lymphocytes to ionizing radiation at 0.

Development of photoprotective, antiphototoxic, and antiphotogenotoxic formulations of ocular drugs with fluoroquinolones.

The development of innovative solutions in photosafety of photolabile pharmaceutical products may help to reduce the adverse effects of these products, caused by light exposure. Providing new data in this area of study is particularly important in case of drugs applied topically on sensitive organs such as eyes. The main goal of this research is to investigate whether two potential excipients, namely: p-coumaric acid and benzophenone-4, affect the photodegradation, phototoxicity and photogenotoxicity of water solutions of four fluoroquinolones: ciprofloxacin, lomefloxacin, fleroxacin and clinafloxacin.

Dose assessment intercomparisons within the RENEB network using G-lymphocyte prematurely condensed chromosomes (PCC assay).

Purpose: Dose assessment intercomparisons within the RENEB network were performed for triage biodosimetry analyzing G-lymphocyte PCC for harmonization, standardization and optimization of the PCC assay.

Materials And Methods: Comparative analysis among different partners for dose assessment included shipment of PCC-slides and captured images to construct dose-response curves for up to 6 Gy γ-rays. Accident simulation exercises were performed to assess the suitability of the PCC assay by detecting speed of analysis and minimum number of cells required for categorization of potentially exposed individuals.

RENEB intercomparisons applying the conventional Dicentric Chromosome Assay (DCA).

Purpose: Two quality controlled inter-laboratory exercises were organized within the EU project 'Realizing the European Network of Biodosimetry (RENEB)' to further optimize the dicentric chromosome assay (DCA) and to identify needs for training and harmonization activities within the RENEB network.

Materials And Methods: The general study design included blood shipment, sample processing, analysis of chromosome aberrations and radiation dose assessment. After manual scoring of dicentric chromosomes in different cell numbers dose estimations and corresponding 95% confidence intervals were submitted by the participants.

Investigation of the influence of calibration practices on cytogenetic laboratory performance for dose estimation.

Purpose: In the frame of the QA program of RENEB, an inter-laboratory comparison (ILC) of calibration sources used in biological dosimetry was achieved to investigate the influence of calibration practices and protocols on the results of the dose estimation performance as a first step to harmonization and standardization of dosimetry and irradiation practices in the European biological dosimetry network.

Materials And Methods: Delivered doses by irradiation facilities used by RENEB partners were determined with EPR/alanine dosimetry system. Dosimeters were irradiated in the same conditions as blood samples.

RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry.

Purpose: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios.

Results: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices.

RENEB biodosimetry intercomparison analyzing translocations by FISH.

Purpose: In the framework of RENEB, several biodosimetry exercises were conducted analyzing different endpoints. Among them, the analysis of translocations is considered the most useful method for retrospective biodosimetry due to the relative stability of their frequency with post irradiation time. The aim of this study was to harmonize the accuracy of translocation-based biodosimetry within the RENEB consortium.

RENEB intercomparison exercises analyzing micronuclei (Cytokinesis-block Micronucleus Assay).

Purpose: In the framework of the 'Realizing the European Network of Biodosimetry' (RENEB) project, two intercomparison exercises were conducted to assess the suitability of an optimized version of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency triages. Twelve European institutions participated in the first exercise, and four non-RENEB labs were added in the second one.

Materials And Methods: Irradiated blood samples were shipped to participating labs, whose task was to culture these samples and provide a blind dose estimate.

Uncertainty of fast biological radiation dose assessment for emergency response scenarios.

Purpose: Reliable dose estimation is an important factor in appropriate dosimetric triage categorization of exposed individuals to support radiation emergency response.

Materials And Methods: Following work done under the EU FP7 MULTIBIODOSE and RENEB projects, formal methods for defining uncertainties on biological dose estimates are compared using simulated and real data from recent exercises.

Results: The results demonstrate that a Bayesian method of uncertainty assessment is the most appropriate, even in the absence of detailed prior information.

RENEB accident simulation exercise.

Purpose: The RENEB accident exercise was carried out in order to train the RENEB participants in coordinating and managing potentially large data sets that would be generated in case of a major radiological event.

Materials And Methods: Each participant was offered the possibility to activate the network by sending an alerting email about a simulated radiation emergency. The same participant had to collect, compile and report capacity, triage categorization and exposure scenario results obtained from all other participants.

Capabilities of the RENEB network for research and large scale radiological and nuclear emergency situations.

Purpose: To identify and assess, among the participants in the RENEB (Realizing the European Network of Biodosimetry) project, the emergency preparedness, response capabilities and resources that can be deployed in the event of a radiological or nuclear accident/incident affecting a large number of individuals. These capabilities include available biodosimetry techniques, infrastructure, human resources (existing trained staff), financial and organizational resources (including the role of national contact points and their articulation with other stakeholders in emergency response) as well as robust quality control/assurance systems.

Materials And Methods: A survey was prepared and sent to the RENEB partners in order to acquire information about the existing, operational techniques and infrastructure in the laboratories of the different RENEB countries and to assess the capacity of response in the event of radiological or nuclear accident involving mass casualties.

Web based scoring is useful for validation and harmonisation of scoring criteria within RENEB.

Purpose: To establish a training data set of digital images and to investigate the scoring criteria and dose assessment of the dicentric assay within the European network of biodosimetry (RENEB), a web based scoring inter-comparison was undertaken by 17 RENEB partners.

Materials And Methods: Two sets of 50 high resolution images were uploaded onto the RENEB website. One set included metaphases after a moderate exposure (1.

Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans - joint RENEB and EURADOS inter-laboratory comparisons.

Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation.

Defining Blood Processing Parameters for Optimal Detection of γ-H2AX Foci: A Small Blood Volume Method.

Biodosimetric methods used to measure the effects of radiation are critical for estimating the health risks to irradiated individuals or populations. The direct measurement of radiation-induced γ-H2AX foci in peripheral blood lymphocytes is one approach that provides a useful end point for triage. Despite the documented advantages of the γ-H2AX assay, there is considerable variation among laboratories regarding foci formation in the same exposure conditions and cell lines.

Evaluation of photodegradation, phototoxicity and photogenotoxicity of ofloxacin in ointments with sunscreens and in solutions.

Fluoroquinolones are widely used anti-bacterial agents that are known to exhibit moderate to severe phototoxicity. Furthermore some of them reveal photogenotoxicity under UV irradiation. Incidence of side effects due to light exposure may be augmented, if the medicament is used topically.

Inter- and intra-laboratory comparison of a multibiodosimetric approach to triage in a simulated, large scale radiation emergency.

Purpose: The European Union's Seventh Framework Programme-funded project 'Multi-disciplinary biodosimetric tools to manage high scale radiological casualties' (MULTIBIODOSE) has developed a multiparametric approach to radiation biodosimetry, with a particular emphasis on triage of large numbers of potentially exposed individuals following accidental exposures. In November 2012, an emergency exercise took place which tested the capabilities of the MULTIBIODOSE project partners. The exercise described here had a dual purpose: Intercomparison of (i) three biodosimetric assays, and (ii) the capabilities of the seven laboratories, with regards to provision of triage status for suspected radiation exposed individuals.

Oxidative DNA damage corresponds to the long term survival of human cells treated with silver nanoparticles.

We examined the relation between DNA damage and the clonogenic potential of 3 human cell lines, HepG2, HT29 and A549, treated with bare 20 nm or 200 nm silver nanoparticles (AgNPs). The endpoints examined were the DNA breakage estimated by the comet assay, the oxidative base damage recognized by formamido-pyrimidine glycosylase (FPG) and estimated with the FPG+comet assay, and the frequencies of histone γH2AX foci and micronuclei. Each cell line studied had a different pattern of DNA breakage and base damage versus the NPs concentration and time of treatment.

Cis-9,trans-11-conjugated linoleic acid affects lipid raft composition and sensitizes human colorectal adenocarcinoma HT-29 cells to X-radiation.

Background: Investigations concerned the mechanism of HT-29 cells radiosensitization by cis-9,trans-11-conjugated linoleic acid (c9,t11-CLA), a natural component of human diet with proven antitumor activity.

Methods: The cells were incubated for 24h with 70μM c9,t11-CLA and then X-irradiated. The following methods were used: gas chromatography (incorporation of the CLA isomer), flow cytometry (cell cycle), cloning (survival), Western blotting (protein distribution in membrane fractions), and pulse-field gel electrophoresis (rejoining of DNA double-strand breaks).

Complex exchanges are responsible for the increased effectiveness of C-ions compared to X-rays at the first post-irradiation mitosis.

The purpose of the present study was to investigate as to what extent differences in the linear energy transfer (LET) are reflected at the chromosomal level. For this study human lymphocytes were exposed to 9.5 MeV/u C-ions (1 or 2 Gy, LET=175 keV/microm) or X-rays (1-6 Gy), harvested at 48, 72 or 96 h post-irradiation and aberrations were scored in first cycle metaphases using 24 color fluorescence in situ hybridization (mFISH).

Chromosomal aberrations in peripheral blood lymphocytes of prostate cancer patients treated with IMRT and carbon ions.

Background And Purpose: To investigate the cytogenetic damage in blood lymphocytes of patients treated for prostate cancer with different radiation qualities and target volumes.

Materials And Methods: Twenty patients receiving carbon-ion boost irradiation followed by IMRT or IMRT alone for the treatment of prostate cancer entered the study. Cytogenetic damage induced in peripheral blood lymphocytes of these patients was investigated at different times during the radiotherapy course using Giemsa staining and mFISH.

Enhanced level of micronuclei in peripheral blood lymphocytes of patients treated for restenosis with 32P endovascular brachytherapy.

Background: Restenosis is the complete occlusion of the blood vessel leading to such complications as ischemia/angina, myocardial infarction, and death. It can be managed by endovascular brachytherapy with both gamma and beta sources. Endovascular brachytherapy is performed worldwide on several thousands of cases per year.