Physicians, hospitals, and other health care facilities will assume the responsibility for aiding individuals injured by a terrorist act involving radioactive material. Scenarios have been developed for such acts that include a range of exposures resulting in few to many casualties. This consensus document was developed by the Strategic National Stockpile Radiation Working Group to provide a framework for physicians in internal medicine and the medical subspecialties to evaluate and manage large-scale radiation injuries. Individual radiation dose is assessed by determining the time to onset and severity of nausea and vomiting, decline in absolute lymphocyte count over several hours or days after exposure, and appearance of chromosome aberrations (including dicentrics and ring forms) in peripheral blood lymphocytes. Documentation of clinical signs and symptoms (affecting the hematopoietic, gastrointestinal, cerebrovascular, and cutaneous systems) over time is essential for triage of victims, selection of therapy, and assignment of prognosis. Recommendations based on radiation dose and physiologic response are made for treatment of the hematopoietic syndrome. Therapy includes treatment with hematopoietic cytokines; blood transfusion; and, in selected cases, stem-cell transplantation. Additional medical management based on the evolution of clinical signs and symptoms includes the use of antimicrobial agents (quinolones, antiviral therapy, and antifungal agents), antiemetic agents, and analgesic agents. Because of the strong psychological impact of a possible radiation exposure, psychosocial support will be required for those exposed, regardless of the dose, as well as for family and friends. Treatment of pregnant women must account for risk to the fetus. For terrorist or accidental events involving exposure to radioiodines, prophylaxis against malignant disease of the thyroid is also recommended, particularly for children and adolescents.

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Medical Management of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group

The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements.

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Review of retrospective dosimetry techniques for external ionising radiation exposures

Pellmar, T. C., Rockwell, S. and the Radiological/Nuclear Threat Countermeasures Working Group. Priority List of Research Areas for Radiological Nuclear Threat Countermeasures. Radiat. Res. 163, 115–123 (2005). To help the nation prepare for the possibility of a terrorist attack using radiological and nuclear devices, the Office of Science and Technology Policy and the Homeland Security Council established an interagency working group. The working group deliberated on the research needs for radiological/ nuclear threat countermeasures and identified and prioritized 18 areas for further attention. The highest priorities were given to research on (1) radioprotectors for use prior to exposure; (2) therapeutic agents for postexposure treatment; (3) antimicrobial therapy for infections associated with radiation exposure; (4) cytokines and growth factors; (5) mechanisms of radiation injury at the molecular, cellular, tissue and organism levels; and (6) automation of biodosimetric assays. High priority ...

Priority List of Research Areas for Radiological Nuclear Threat Countermeasures

The events that followed the Tohoku earthquake and tsunami on March 11, 2011, included the loss of power and overheating at the Fukushima Daiichi nuclear power plants, which led to extensive releases of radioactive gases, volatiles, and liquids, particularly to the coastal ocean. The fate of these radionuclides depends in large part on their oceanic geochemistry, physical processes, and biological uptake. Whereas radioactivity on land can be resampled and its distribution mapped, releases to the marine environment are harder to characterize owing to variability in ocean currents and the general challenges of sampling at sea. Five years later, it is appropriate to review what happened in terms of the sources, transport, and fate of these radionuclides in the ocean. In addition to the oceanic behavior of these contaminants, this review considers the potential health effects and societal impacts.

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Fukushima Daiichi–Derived Radionuclides in the Ocean: Transport, Fate, and Impacts

Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100 mSv and/or 0.1 mSv min−1) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential.

Ionizing radiation biomarkers for potential use in epidemiological studies.

A dose estimation by chromosome analysis was performed on the 3 severely exposed patients in the Tokai-mura criticality accident. Drastically reduced lymphocyte counts suggested that the whole-body dose of radiation which they had been exposed to was unprecedentedly high. Because the number of lymphocytes in the white blood cells in two patients was very low, we could not culture and harvest cells by the conventional method. To collect the number of lymphocytes necessary for chromosome preparation, we processed blood samples by a modified method, called the high-yield chromosome preparation method. With this technique, we could culture and harvest cells, and then make air-dried chromosome slides. We applied a new dose-estimation method involving an artificially induced prematurely condensed ring chromosome, the PCC-ring method, to estimate an unusually high dose with a short time. The estimated doses by the PCC-ring method were in fairly good accordance with those by the conventional dicentric and ring chromosome (Dic+R) method. The biologically estimated dose was comparable with that estimated by a physical method. As far as we know, the estimated dose of the most severely exposed patient in the present study is the highest recorded among that chromosome analyses have been able to estimate in humans.

Cytogenetical Dose Estimation for 3 Severely Exposed Patients in the JCO Criticality Accident in Tokai-mura

Purpose : To propose a practical method of biodosimetry for highdose estimation. Materials and methods : Okadaic acid in the range 100nm to 500nm was given for 1-6h to cultured lymphocytes that had been exposed in the range of 0Gy to 40Gy. The frequency of the cells with prematurely condensed chromosomes (PCC) was compared with that of metaphases accumulated by 0.05 mu g/ml colcemid. The dose-response relationship of the yield of prematurely condensed ring chromosomes (PCC rings) in the irradiated lymphocytes was examined. Results : The 0.05 mu g/ml colcemid collected few metaphases when lymphocytes were irradiated to over 10Gy. However, 500nm okadaic acid produced a substantial number of analysable PCC in lymphocytes that had been exposed in the range of 0Gy to 40Gy. After 1h of treatment, the 500nm okadaic acid gave the most suitable chromosome morphology for the analysis. PCC rings were narrow, which facilitated their detection in Giemsastained preparations. The yield of PCC rings increased dosedepende...

Easy biodosimetry for high-dose radiation exposures using drug-induced, prematurely condensed chromosomes.

Purpose : To investigate the dynamics of chromosome aberrations in the blood cells of three workers severely exposed to neutrons and γ-rays in a criticality accident that occurred in Tokai-mura, Japan, in 1999. Materials and methods : The change with time of the frequency of chromosome aberrations in the three patients was examined using a new analysis to score drug-induced prematurely condensed ring chromosomes (PCC-R) and a conventional metaphase analysis. Results : The frequencies and cellular distributions of PCC-R, dicentrics and rings did not change significantly among the samples obtained at 9-48 h after the accident while the first depletion of lymphocytes occurred. The distributions of these aberrations in the cells of two patients showed a slight overdispersion compared with a Poisson distribution reflecting neutron and non-uniform exposures. The dose-response curve of rings paralleled that of dicentrics, but not PCC-R. The half-lives of PCC-R (8.5 months) and of rings (8.7 months) were shorter ...

Dynamic analysis of chromosome aberrations in three victims of the Tokai-mura criticality accident

As a part of technical improvements of chromosome aberration analysis on human peripheral lymphocytes for biological radiation dosimetry, we examined the optimal conditions for the use of colcemid in chromosome preparation in order to obtain enough number of cells at metaphase in the first cell division. When treated with colcemid at concentrations below 0.01 microgram/ml from the beginning of culture, cultures harvested at 48 hours had low mitotic indices. Colcemid treatment at 0.025 to 0.05 microgram/ml during 48 hours resulted in high mitotic indices (8 to 15%) and almost of the mitotic cells remaining in the 1st cell division, suggesting that this range of colcemid concentration was appropriate for continuous treatment with colcemid. We further examined the effect of colcemid concentration on the quantitative consistency of the yields of radiation-induced chromosome aberration. Repeated experiments showed that the yield of dicentrics and centric rings in the culture having colcemid at 0.025 microgram/ml concentration were larger than that at 0.05 microgram/ml. These data indicate the importance of assuring the accuracy of colcemid concentration in the lymphocyte culture for cytogenetic radiation dosimetry.

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Effects of Colcemid Concentration on Chromosome Aberration Analysis in Human Lymphocytes

Inconsistent results have been reported regarding the yields of translocations and dicentrics measured using chromosome painting. This inconsistency may be due to mis-scoring of dicentrics as translocations because painting is unsuited to identify centromere positions. In the present study, chromosome aberrations exclusively in the first mitosis after irradiation were analyzed using human peripheral lymphocytes. When identical metaphases were analyzed by both painting and conventional Giemsa staining, which is the most reliable method to locate centromeres, equal frequencies of translocations and dicentrics were observed.

Reiko Kanda

Papers

Cytogenetical Dose Estimation for 3 Severely Exposed Patients in the JCO Criticality Accident in Tokai-mura

Easy biodosimetry for high-dose radiation exposures using drug-induced, prematurely condensed chromosomes.

Dynamic analysis of chromosome aberrations in three victims of the Tokai-mura criticality accident

Effects of Colcemid Concentration on Chromosome Aberration Analysis in Human Lymphocytes

Comparison of the yields of translocations and dicentrics measured using conventional Giemsa staining and chromosome painting