Radioprotective Effects from Propolis: A Review.

Propolis is a natural bee-produced substance with antimicrobial, anti-inflammatory, and wound-healing properties, containing some components from the leaves, buds and resins of plants. It has been used for centuries for various health benefits. In this manuscript, our group reviewed the radioprotective effect of propolis using PubMed and Embase, and our review was conducted according to the PRISMA statement. Finally, 27 articles were included in this review, which includes the radioprotective effect of propolis from cell-based studies (n = 8), animal models (n = 14), and human trials (n = 5). Results reflected that the dosage forms of propolis extracted in the scientific literature were ethanolic extracts of propolis, a water-soluble derivate of propolis, or capsules. The efficacy of the radioprotective properties from propolis is extracted from the bibliography, as several compounds of this resinous mixture individually or synergistically are possible candidates that have the radioprotective effect. In fact, studies prior to 2011 lacked a comprehensive characterization of propolis due to the variability in active compounds among different batches of propolis and were limited to analytical techniques. Furthermore, in this manuscript, we have selected studies to include primarily propolis types from Brazil, Croatia, Egypt, European countries, and those commercialized in Spain. They all contained ethanolic extract of propolis (EEP) and were influenced by different dosage forms. EEP showed a significant presence of lipophilic bioactive compounds like flavones, flavonols, and flavanones.

A Narrative Review of the Herbal Preparation of Ayurvedic, Traditional Chinese, and Kampo Medicines Applied as Radioprotectors.

In recent years, there has been growing scientific interest in the search for natural radioprotectors that can be used to mitigate the effects of radiation on patients, healthcare personnel, and even for space travel. This narrative review covers the past fifty years and focuses on herbal preparations of Ayurvedic, Traditional Chinese, and Kampo Medicines that have the potential to reduce or eliminate the harmful effects of radiation. Our findings highlight ten herbal preparations, namely Abana, Amalakyadi Churna, Amritaprasham, Brahma, Bu-zhong-yi-qi-tang (BZYQT), Chyavanaprasha, Cystone, Geriforte, Mentat, and Triphala, which have demonstrated potential radioprotective effects. This review examines their composition, properties, and possible mechanisms of action in relation to their radioprotective properties. Exploring the ethnobotany of traditional Asian medicine is particularly interesting as it may lead to the discovery of new active compounds with radioprotective properties.

Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators.

Ionizing radiation (IR) is the energy released by atoms in the form of electromagnetic waves (e [...].

Vitamins and Radioprotective Effect: A Review.

The radioprotective effect ex vivo, in vitro and in vivo of vitamins was reviewed using PubMed and Embase and conducted according to the PRISMA statement. A total of 38 articles were included in this review, which includes the radioprotective effect of vitamins from ex vivo, in vitro and in vivo studies. Vitamins A, C, D and E were used alone, in combination or with other nutritional and non-nutritional compounds. The use of vitamins in natural form or supplementation can be useful to reduce the radiation effect in the body, organs and/or cells. Only four (A, C, D and E) out of thirteen vitamins have been detected with radioprotective properties being mainly vitamin E followed by vitamin C, A and D.

Combination of natural polyphenols with a precursor of NAD+ and a TLR2/6 ligand lipopeptide protects mice against lethal γ radiation.

INTRODUCTION: Effective agents that could confer long-term protection against ionizing radiation in vivo would have applications in medicine, biotechnology, and in air and space travel. However, at present, drugs that can effectively protect against lethal ionizing radiations are still an unmet need. OBJECTIVE: To investigate if combinations of natural polyphenols, known for their antioxidant potential, could protect against ionizing radiations. METHODS: Plant-derived polyphenols were screened for their potential ability to confer radioprotection to mice given a lethal whole-body γ radiation (137Cs) dose expected to kill 50% of the animals in 30 days. Telomere and centromere staining, Q-FISH and comet assays were used to investigate chromosomal aberration, micronuclei formation and DNA breaks. Molecular oxidations were investigated by enzyme immunoassays and UPLC-MS/MS. RT-PCR, western blotting and siRNA-induced gene silencing were used to study signaling mechanisms and molecular interactions. RESULTS: The combination of pterostilbene (PT) and silibinin (SIL) was the most effective against γ-irradiation, resulting in 100% of the mice surviving at 30 days and 20% survival at one year. Treatment post γ-irradiation with two potential radiomitigators nicotinamide riboside (NR, a vitamin B3 derivative), and/or fibroblast-stimulating lipoprotein 1 (FSL1, a toll-like receptor 2/6 agonist), did not extend survival. However, the combination of PT, SIL, NR and FSL1 achieved a 90% survival one year post γ-irradiation. The mechanism involves induction of the Nrf2-dependent cellular antioxidant defense, reduction of NF-kB signaling, upregulation of the PGC-1α/sirtuins 1 and 3 axis, PARP1-dependent DNA repair, and stimulation of hematopoietic cell recovery. The pathway linking Nrf2, sirtuin 3 and SOD2 is key to radioprotection. Importantly, this combination did not interfere with X-ray mediated killing of different tumor cells in vivo. CONCLUSION: The combination of the radioprotectors PT and SIL with the radiomitigators NR and FSL1 confer effective, long-term protection against γ radiation in vivo. This strategy is potentially capable of protecting mammals against ionizing radiations.

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry.

Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms.

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 1.36 TBq 192Ir-source. For each exposure condition, dose estimates were provided by at least one laboratory and for four conditions by 17 participating RENEB laboratories. Three radio-photoluminescence glass dosimeters were placed at each tube to assess reference doses. RESULTS: The DCA results were homogeneous between participants and matched well with the reference doses (≥95% of estimates within ±0.5 Gy of the reference). For samples close to the source systematic underestimation could be corrected by accounting for exposure time. Heterogeneity within and between tubes was detected for reference doses as well as for DCA doses estimates. CONCLUSIONS: The participants were able to successfully estimate the doses and to provide important information on the exposure scenarios under conditions closely resembling a real-life situation.

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. At the European level, a great effort has been made to harmonize biological dosimetry laboratories, notably during the MULTIBIODOSE and RENEB projects. In order to continue the harmonization efforts, the RENEB consortium launched this intercomparison which is larger than the RENEB network, as it involves 38 laboratories from 21 countries. In this ILC all steps of the process were monitored, from blood shipment to dose estimation. This exercise also aimed to evaluate the statistical tools used to compare laboratory performance. MATERIALS AND METHODS: Blood samples were irradiated at three different doses, 1.8, 0.4 and 0 Gy (samples A, C and B) with 4-MV X-rays at 0.5 Gy min-1, and sent to the participant laboratories. Each laboratory was requested to blindly analyze 500 cells per sample and to report the observed frequency of dicentric chromosomes per metaphase and the corresponding estimated dose. RESULTS: This ILC demonstrates that blood samples can be successfully distributed among laboratories worldwide to perform biological dosimetry in case of a mass casualty event. Having achieved a substantial harmonization in multiple areas among the RENEB laboratories issues were identified with the available statistical tools, which are not capable to advantageously exploit the richness of results of a large ILCs. Even though Z- and U-tests are accepted methods for biodosimetry ILCs, setting the number of analyzed metaphases to 500 and establishing a tests' common threshold for all studied doses is inappropriate for evaluating laboratory performance. Another problem highlighted by this ILC is the issue of the dose-effect curve diversity. It clearly appears that, despite the initial advantage of including the scoring specificities of each laboratory, the lack of defined criteria for assessing the robustness of each laboratory's curve is a disadvantage for the 'one curve per laboratory' model. CONCLUSIONS: Based on our study, it seems relevant to develop tools better adapted to the collection and processing of results produced by the participant laboratories. We are confident that, after an initial harmonization phase reached by the RENEB laboratories, a new step toward a better optimization of the laboratory networks in biological dosimetry and associated ILC is on the way.

Radioprotection and Radiomitigation: From the Bench to Clinical Practice.

The development of protective agents against harmful radiations has been a subject of investigation for decades. However, effective (ideal) radioprotectors and radiomitigators remain an unsolved problem. Because ionizing radiation-induced cellular damage is primarily attributed to free radicals, radical scavengers are promising as potential radioprotectors. Early development of such agents focused on thiol synthetic compounds, e.g., amifostine (2-(3-aminopropylamino) ethylsulfanylphosphonic acid), approved as a radioprotector by the Food and Drug Administration (FDA, USA) but for limited clinical indications and not for nonclinical uses. To date, no new chemical entity has been approved by the FDA as a radiation countermeasure for acute radiation syndrome (ARS). All FDA-approved radiation countermeasures (filgrastim, a recombinant DNA form of the naturally occurring granulocyte colony-stimulating factor, G-CSF; pegfilgrastim, a PEGylated form of the recombinant human G-CSF; sargramostim, a recombinant granulocyte macrophage colony-stimulating factor, GM-CSF) are classified as radiomitigators. No radioprotector that can be administered prior to exposure has been approved for ARS. This differentiates radioprotectors (reduce direct damage caused by radiation) and radiomitigators (minimize toxicity even after radiation has been delivered). Molecules under development with the aim of reaching clinical practice and other nonclinical applications are discussed. Assays to evaluate the biological effects of ionizing radiations are also analyzed.

Redox Status, Dose and Antioxidant Intake in Healthcare Workers Occupationally Exposed to Ionizing Radiation.

The purpose of this study was to evaluate the relationship between blood redox status, dose and antioxidant dietary intake of different hospital staff groups exposed to low doses of ionizing radiation (LDIR) (Interventional Radiology and Cardiology, Radiation Oncology, and Nuclear Medicine) and non-exposed. Personal dose equivalent (from last year and cumulative), plasma antioxidant markers (total antioxidant capacity, extracellular superoxide dismutase activity, and glutathione/oxidized glutathione ratio), oxidative stress markers (nitrites and nitrates, and lipid peroxidation) and dietary intake (antioxidant capacity using ORAC values) were collected and analyzed from 28 non-exposed healthcare workers and 42 healthcare workers exposed to LDIR. Hospital staff exposed to LDIR presented a redox imbalance in blood that seems to correlate with dose. Workers from the Nuclear Medicine Unit were the most affected group with the lowest value of plasma antioxidant response and the highest value of plasma thiobarbituric acid reactive substances, TBARS (indicator of lipid peroxidation) of all four groups. Cumulative personal dose equivalent positively correlated with nitrites and negatively correlated with total antioxidant capacity in blood. The diet of healthcare workers from Nuclear Medicine Unit had higher ORAC values than the diet of non-exposed. Therefore, occupational exposure to LDIR, especially for the Nuclear Medicine Unit, seems to produce an imbalanced redox status in blood that would correlate with cumulative personal dose equivalent.

Use of Ganoderma lucidum (Ganodermataceae, Basidiomycota) as Radioprotector.

For millennia, naturopaths and physicians have used Ganoderma lucidum (reishi mushroom) for its diverse therapeutic properties, as recorded in the oldest Chinese herbal encyclopedia. Indeed, a radioprotective effect has been reported in the isolated components of its extracts. A systematic review and meta-analyses (PRISMA) was conducted in March 2020, searching databases including PubMed, Scopus, Embase, and Google Scholar, along with Clinical Trials. The inclusion criteria were ex vivo, in vitro, and in vivo studies, with full texts in English, conducted to determine the radioprotective benefits of G. lucidum, or reports in which ionizing radiation was used. From a total number of 1109 records identified, 15 full text articles were eligible, none of them were clinical trials. In vivo studies reveal the efficiency of G. lucidum aqueous extracts of polysaccharides and triterpenes in mice exposed to γ-rays. In plasmid, they can reduce radiation damage as an increment of the open circular form, as well as increase the DNA extension, as shown in vitro studies. Ex vivo studies conducted in human blood cells show the radioprotective effect of ß-glucan of aqueous extract of G. lucidum, nevertheless, its implementation as radioprotector to humans is in need of further clinical research studies.

Measurement of body composition in cancer patients using CT planning scan at the third lumbar vertebra.

INTRODUCTION: Objective: the main objective was to assess body composition in terms of skeletal muscle index (SMI), myosteatosis, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) as an adjunct of information provided by radiotherapy CT planning scan. Material and methods: a sample of 49 patients with lung and digestive cancers underwent a CT scan for radiotherapy treatment, which included measurements at the L3 region. Images were analyzed with a radiotherapy contouring software, using different Hounsfield Unit (HU) settings. Cross-sectional areas (cm2) were automatically computed by summing tissue pixels and multiplying by pixel surface area. Low SMI (cm2/m2) and muscle density (HU) were determined according to the recently established cut-off points. Results: the prevalence of low SMI was detected in 46.94% of patients, being present in 8 women, 4 men with BMI < 25 kg/m2, and 11 men with BMI ≥ 25 kg/m2. The average mean skeletal attenuation of total skeletal muscle area was 29.02 (± 8.66) HU, and myosteatosis was present in 13 women (81.25%) and 31 men (93.94%). Mean SAT was 131.92 (± 76.80) cm2, mean VAT was 133.19 (± 85.28) cm2, and mean IMAT was 11.29 (± 12.86) cm2. Conclusion: skeletal muscle abnormalities are frequently present in cancer patients and a low SMI may also exist even in the presence of overweight. As CT scans are an important tool at any radiation oncology department, they could also be used to offer highly sensitive and specific information about body composition, as well as to detect early malnutrition before starting radiotherapy treatment.

INTRODUCCIÓN: Objetivo: evaluar la composición corporal mediante el índice de músculo esquelético (IME), el tejido adiposo visceral (TAV), el tejido adiposo subcutáneo (TAS) y el tejido adiposo intermuscular (TAIM) o la densidad muscular (DM) en pacientes oncológicos antes de iniciar el tratamiento con radioterapia mediante cortes de TAC. Materiales y métodos: se estudiaron 49 pacientes con cáncer de pulmón y del aparato digestivo sometidos a tomografía computarizada con cortes en L3 para la determinación del tratamiento con radioterapia. El tejido adiposo y muscular se cuantificó mediante distintas Unidades Hounsfield (UH) (-29 a +150 para masa muscular, -190 a -30 para TAIM/TAS y -150 a -50 para TAV). Resultados: la prevalencia de un IME bajo se detectó en el 46,94% de los pacientes, estando presente en 8 mujeres, 6 de ellas con un IMC ≥ 25 kg/m². Según la distribución masculina, se identificaron 4 hombres con IMC < 25 kg/m² y 11 hombres con ≥ 25 kg/m². La DM media fue de 29,02 (± 8,66) UH y la mioesteatosis estuvo presente en 13 mujeres (81,25%) y 31 hombres (93,94%). La media del TAS fue de 131,92 (± 76,80) cm², la del TAV de 133,19 (± 85,28) cm² y la del TAIM de 11,29 (± 12,86) cm². Conclusión: las anormalidades del músculo esquelético y la masa grasa son muy frecuentes en los pacientes con cáncer, pudiendo existir un bajo IME incluso en presencia de sobrepeso u obesidad. Teniendo en cuenta que la TAC es una herramienta importante en cualquier departamento de radioterapia, también podría utilizarse para ofrecer información sensible y específica sobre la composición corporal, así como para detectar la malnutrición precoz.

Diagnosis of pre-sarcopenia from a single selectional crosscut at C3 region, using CT scans before radiotherapy.

INTRODUCTION: Purpose: the main purpose of this study was to diagnose pre-sarcopenia in cancer patients who had lack of computed tomography (CT) abdominal images, with a newly discovered method based on cervical images. Material and methods: a sample of 37 patients with either lung cancer or a cancer that affected the upper digestive system underwent radiotherapy computed simulation which included measurements at C3 and L3 regions. Skeletal muscle mass (SMM) and skeletal muscle index (SMI) were determined by Hounsfield units and compared in both regions. Pre-sarcopenia was identified according to the cut-points currently established: ≤ 41 cm2/m2 in females, ≤ 43 cm2/m2 in males with a BMI ≤ 25 kg/m2, and ≤ 53 cm2/m2 in males with a BMI > 25 kg/m2. Results: the correlation of SMM and SMI between the C3 and L3 regions was R2 = 0.876 and R2 = 0.805, respectively. Moreover, there was a positive association (86.49%) in terms of the diagnosis of pre-sarcopenia according to both regions. In total, eleven pre-sarcopenic patients (29.37%) were identified; three of them being overweight (27.27%) and two of them being obese (18.18%). Conclusion: a single sectional cross at the level of C3 can be used for the diagnosis of pre-sarcopenia. This new method avoids unnecessary irradiation, saves hospital costs and detects malnutrition before starting radiotherapy treatment in cancer patients who have lack of CT abdominal imaging.

INTRODUCCIÓN: Propósito: el propósito de este estudio fue diagnosticar la presarcopenia en pacientes con cáncer que no disponen de imágenes por tomografía computarizada (TC) a nivel abdominal mediante un método novedoso basado en cortes a nivel cervical. Material y métodos: se analizaron y se compararon mediante unidades la masa muscular y la masa muscular esquelética en 37 pacientes con cáncer de pulmón y neoplasias del aparato digestivo superior que incluían cortes en la TC de planificación a nivel de C3 y L3. La presarcopenia se identificó de acuerdo con los puntos de corte establecidos actualmente: ≤ 41 cm2/m2 para mujeres, ≤ 43 cm2/m2 en hombres con un IMC ≤ 25 kg/m2 y ≤ 53 cm2/m2 en hombres con IMC > 25 kg/m2. Resultados: la correlación de la masa muscular y el índice musculoesquelético entre las regiones C3 y L3 fue R2 = 0.876 y R2 = 0.805, respectivamente. Además, hubo una asociación positiva (86,49%) en términos del diagnóstico de presarcopenia según ambas regiones. En total, se identificaron once pacientes con presarcopenia (29,37%); tres de ellos con sobrepeso (27,27%) y dos con obesidad (18,18%). Conclusión: un solo corte transversal a nivel de la vértebra C3 puede diagnosticar la presarcopenia. Este nuevo método evita la irradiación innecesaria, ahorra costos hospitalarios y detecta la desnutrición antes de iniciar el tratamiento de radioterapia en pacientes con cáncer que no disponen de imágenes a nivel abdominal.

Assessment of the dicentric chromosome assay as a biodosimetry tool for more personalized medicine in a case of a high risk neuroblastoma 131I-mIBG treatment.

PURPOSE: The aims of this study were to estimate the whole - body absorbed - dose with the Dicentric Chromosome Assay (DCA) (biodosimetry) for 131I - metaiodobenzylguanidine (131I - mIBG) therapy for high - risk neuroblastoma, and to obtain an initial correlation with the physical dosimetry calculated as described by the Medical Internal Radiation Dosimetry formalism (MIRD). Together both objectives will aid the optimization of personalized targeted radionuclide therapies. MATERIAL AND METHODS: A 12 year-old child with relapsed high-risk neuroblastoma was treated with 131I-mIBG: a first administration with activity <444 MBq/kg was used as a tracer in order to calculate the activity needed in a second administration to achieve a whole body prescribed dose of ∼4 Gy. Blood samples were obtained before and seven days after each administration to analyze the frequency of dicentrics. Moreover, consequent estimations of retained activity were done every few hours from equivalent dose rate measurements at a fixed position, two meters away from the patient, in order to apply the MIRD procedure. Blood samples were also drawn every 2- to -3 days to assess bone marrow toxicity. RESULTS: For a total activity of 22,867 MBq administered over two phases, both biological and physical dosimetries were performed. The former estimated a whole-body cumulated dose of 3.53 (2.58-4.41) Gy and the latter a total whole-body absorbed dose of 2.32 ± 0.48 Gy. The patient developed thrombocytopenia grade 3 after both infusions and neutropenia grade 3 and grade 4 (based on CTCAE 4.0) during respective phases. CONCLUSION: The results indicate a possible correlation between biodosimetry and standard physical dosimetry in 131I-mIBG treatment for high-risk neuroblastoma. A larger cohort and refinement of the DCA for internal irradiation are needed to define the role of biodosimetry in clinical situations.

Searching trans-resveratrol in fruits and vegetables: a preliminary screening.

Resveratrol is a phytoalexin with potent anti-inflammatory, anti-oxidant and anti-carcinogenic effects. The object of this work was to determine whether this promising compound was present in the typical fruits and vegetables used in the Mediterranean diet. Our results indicated the presence of trans-resveratrol in concentrations ranging from 0.2 µg/g in tomatoes and 3 lg/g. in strawberries.

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. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. CONCLUSIONS: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.

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. RESULTS: The shipment of blood samples to the partners in the European Community (EU) were performed successfully. Outside the EU unacceptable delays occurred. The results of the dose estimation demonstrate a very successful classification of the blood samples in medically relevant groups. In comparison to the 1st exercise the 2nd intercomparison showed an improvement in the accuracy of dose estimations especially for the high dose point. CONCLUSIONS: In case of a large-scale radiological incident, the pooling of ressources by networks can enhance the rapid classification of individuals in medically relevant treatment groups based on the DCA. The performance of the RENEB network as a whole has clearly benefited from harmonization processes and specific training activities for the network partners.

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 (1.3 Gy) and the other set consisted of metaphases after a high dose exposure (3.5 Gy). The laboratories used their own calibration curves for estimating doses based on observed aberration frequencies. RESULTS: The dose estimations and 95% confidence limits were compared to the actual doses and the corresponding z-values were satisfactory for the majority; only the dose estimations from two laboratories were too low or too high. The coefficients of variation were 17.6% for the moderate and 11.2% for the high dose. Metaphases with controversial results could be identified for training purposes. CONCLUSIONS: Overall, the web based scoring of the two galleries by the 17 laboratories produced very good results. Application of web based scoring for the dicentric assay may therefore be a relevant strategy for an operational biodosimetry assistance network.

Dose assessment intercomparisons within the RENEB network using G0-lymphocyte prematurely condensed chromosomes (PCC assay).

PURPOSE: Dose assessment intercomparisons within the RENEB network were performed for triage biodosimetry analyzing G0-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. RESULTS: Calibration data based on Giemsa-stained fragments in excess of 46 PCC were obtained by different partners using galleries of PCC images for each dose-point. Mean values derived from all scores yielded a linear dose-response with approximately 4 excess-fragments/cell/Gy. To unify scoring criteria, exercises were carried out using coded PCC-slides and/or coded irradiated blood samples. Analysis of samples received 24 h post-exposure was successfully performed using Giemsa staining (1 excess-fragment/cell/Gy) or centromere/telomere FISH-staining for dicentrics. CONCLUSIONS: Dose assessments by RENEB partners using appropriate calibration curves were mostly in good agreement. The PCC assay is quick and reliable for whole- or partial-body triage biodosimetry by scoring excess-fragments or dicentrics in G0-lymphocytes. Particularly, analysis of Giemsa-stained excess PCC-fragments is simple, inexpensive and its automation could increase throughput and scoring objectivity of the PCC assay.

Analysis of the Possible Persistent Genotoxic Damage in Workers Linked to the Ardystil Syndrome.

BACKGROUND: A combination of several factors including a change in the paint application system; a lack of proper hygiene; and inadequate safety measures caused a severe health impact in the workers of some textile painting factories. This outbreak, mainly characterized by respiratory disorders, caused the death of six people and it has been classified as Ardystil syndrome. MATERIALS AND METHODS: Fifty-two workers involved in the outbreak and 48 healthy subjects not known to have exposed to the potentially mutagenic agents participated in the study. The program evaluated possible genotoxic damage through the sister chromatid exchange (SCE) cytogenetic biomarker assay. We determined the frequency of SCE, high-frequency cells (HFCs), and a ratio, which can be considered as a new parameter, allowing for the study of the SCE distribution pattern among the chromosomes. RESULTS: There was no statistically significant difference in the SCE frequency and in the mean number of HFCs between the control and the Ardystil-affected groups. However, smoking increased the incidence of all parameters studied in both the case and control groups. CONCLUSIONS: This study shows that workers involved in the Ardystil syndrome did not suffer genotoxic damage as measured by SCE and HFCs when compared with the control group.