Acute Radiation Effects, the H-ARS in the Non-human Primate: A Review and New Data for the Cynomolgus Macaque with Reference to the Rhesus Macaque.

Medical countermeasure development under the US Food and Drug Administration animal rule requires validated animal models of acute radiation effects. The key large animal model is the non-human primate, rhesus macaque. To date, only the rhesus macaque has been used for both critical supportive data and pivotal efficacy trials seeking US Food and Drug Administration approval.

Co-exposure to internal and external radiation alters cesium biokinetics and retention in mice.

Exposures in post-accidental situations are complex and include both external exposure and internal contamination with several radionuclides. However, in vivo and in vitro studies generally use simplified exposures, while a recent study suggested that combined external irradiation and internal contamination may induce more severe biological effects compared to single exposures. In an attempt to test the hypothesis of potential non-additive effects of multiple radiological exposures, we used a mouse model of combined external x-ray irradiation at 1 and 5 Gy and internal contamination with injection of 20 KBq Cs.

Hto, Tritiated Amino Acid Exposure and External Exposure Induce Differential Effects on Hematopoiesis and Iron Metabolism.

The increased potential for tritium releases from either nuclear reactors or from new facilities raises questions about the appropriateness of the current ICRP and WHO recommendations for tritium exposures to human populations. To study the potential toxicity of tritium as a function of dose, including at a regulatory level, mice were chronically exposed to tritium in drinking water at one of three concentrations, 10 kBq.l, 1 MBq.

Biokinetics and dose assessment after iodine intake in a thyroidectomised rat model.

Procedures using iodine-131 represent more than 90% of all therapies in nuclear medicine in Algeria. It is important to evaluate the long-term biological effects of iodine treatment on non-target organs to improve patient radiation protection. This experimental radiotoxicology study aims to determine the biokinetic models of iodine contamination.

RODES software for dose assessment of rats and mice contaminated with radionuclides.

In order to support animal experiments of chronic radionuclides intake with realistic dosimetry, voxel-based three-dimensional computer models of mice and rats of both sexes and three ages were built from magnetic resonance imaging. Radiation transport of mono-energetic photons of 11 energies and electrons of 7 energies was simulated with MCNPX 2.6c to assess specific absorbed fractions (SAFs) of energy emitted from 13 source regions and absorbed in 28 target regions.

Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers.

The presence of Cesium (Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l) and tested contaminations lasting 9 months for adult, neonatal and fetal rats.

Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure.

The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear.

Immune System Modifications Induced in a Mouse Model of Chronic Exposure to (90)Sr.

Strontium 90 ((90)Sr) remains in the environment long after a major nuclear disaster occurs. As a result, populations living on contaminated land are potentially exposed to daily ingesting of low quantities of (90)Sr. The potential long-term health effects of such chronic contamination are unknown.

Unexpected lack of deleterious effects of uranium on physiological systems following a chronic oral intake in adult rat.

Uranium level in drinking water is usually in the range of microgram-per-liter, but this value may be as much as 100 to 1000 times higher in some areas, which may raise question about the health consequences for human populations living in these areas. Our purpose was to improve knowledge of chemical effects of uranium following chronic ingestion. Experiments were performed on rats contaminated for 9 months via drinking water containing depleted uranium (0.

Chronic exposure to low concentrations of strontium 90 affects bone physiology but not the hematopoietic system in mice.

The aim of this work was to delineate the effects of chronic ingestion of strontium 90 ((90) Sr) at low concentrations on the hematopoiesis and the bone physiology. A mouse model was used for that purpose. Parent animals ingested water containing 20 kBq l(-1) of (90) Sr two weeks before mating.

Biokinetics of 90Sr after chronic ingestion in a juvenile and adult mouse model.

The aim of our study was to define the biokinetics of (90)Sr after chronic contamination by ingestion using a juvenile and adult murine model. Animals ingested (90)Sr by drinking water containing 20 kBq l(-1) of (90)Sr. For the juvenile model, parents received (90)Sr before mating and their offspring were killed between birth and 20 weeks of ingestion.

Influence on the mouse immune system of chronic ingestion of 137Cs.

The aim of this work was to determine the possible occurrence of damage to the immune system during the course of chronic ingestion of (137)Cs. BALB/C mice were used, with (137)Cs intake via drinking water at a concentration of 20 kBq l(-1). Adults received (137)Cs before mating and offspring were sacrificed at various ages between birth and 20 weeks.

Distribution of 137Cs in rat tissues after various schedules of chronic ingestion.

The aim of this work was to compare the distribution of 137Cs in organisms after chronic ingestion following different schedules. Rats were contaminated through drinking water containing 6,500 Bq L(-1) of 137Cs, starting either at birth, at weaning, or upon reaching adult age (13 wk). Animals were then sacrificed after different durations of ingestion.

European consensus on the medical management of acute radiation syndrome and analysis of the radiation accidents in Belgium and Senegal.

A European consensus concerning the medical management of mass radiation exposure was obtained in 2005 during a conference held by the European Group for Blood and Bone Marrow Transplantation, the Institute of Radioprotection and Nuclear Safety, and the University of Ulm. At the conference, a two-step triage strategy to deal with large masses of radiation-exposed patients was designed. The first step of this strategy concerns the first 48 h and involves scoring the patients exclusively on the basis of their clinical symptoms and biological data.

Biodistribution of (137)Cs in a mouse model of chronic contamination by ingestion and effects on the hematopoietic system.

The aim of this work was to define the possible occurrence of hematological changes during the course of a chronic ingestion of (137)Cs. A mouse model was used, with ingestion through drinking water with a cesium concentration of 20 kBq l(-1). Ingestion started in parent animals before mating, and (137)Cs intake and its effect on the hematopoietic system was studied in offspring at various ages between birth and 20 weeks.

Synopsis of partial-body radiation diagnostic biomarkers and medical management of radiation injury workshop.

Radiation exposures from accidents, nuclear detonations or terrorist incidents are unlikely to be homogeneous; however, current biodosimetric approaches are developed and validated primarily in whole-body irradiation models. A workshop was held at the Armed Forces Radiobiology Research Institute in May 2008 to draw attention to the need for partial-body biodosimetry, to discuss current knowledge, and to identify the gaps to be filled. A panel of international experts and the workshop attendees discussed the requirements and concepts for a path forward.

Initial evaluation and follow-up of acute radiation syndrome in two patients from the Dakar accident.

The aim of this work was to evaluate and follow up the evolution of radiation damage in two victims of a radiation accident. Blood samples were used for cytogenetic evaluation of radiation dose and heterogeneity. The radiation dose estimates were 1 Gy and 2.

Characterization and histological localization of multipotent mesenchymal stromal cells in the human postnatal thymus.

The aim of this work was to characterize multipotent mesenchymal stromal cells (MSCs) in the postnatal human thymus and to localize these MSCs in the organ. Adherent cells isolated from thymus samples were characterized by cell-surface antigen expression. This showed that adherent cells have a MSC profile as assessed by the expression of CD73 and CD105 markers and the lack of CD45 expression.

Bone marrow stromal cells spontaneously produce Flt3-ligand: influence of ionizing radiations and cytokine stimulation.

Purpose: To define the ability of human bone marrow (BM) stromal cells to produce fms-like tyrosine kinase 3 (Flt3)-ligand (FL), and the effect of irradiation, tumour necrosis factor-alpha (TNFalpha) or tumour growth factor beta (TGFbeta) on FL production.

Material And Methods: Primary BM stromal cell cultures were irradiated at 2-10 Gy or were stimulated with TNFalpha or TGFbeta1. The presence of FL was tested in culture supernatants and in cell lysate.

Correlation between plasma Flt3-ligand concentration and hematopoiesis during G-CSF-induced CD34+ cell mobilization.

This study aimed to correlate blood Flt3-ligand (FL) concentration with CD34(+) cell number in blood and bone marrow (BM) during granulocyte colony-stimulating factor (G-CSF) mobilization. Nonhuman primates were injected with 10 microg/kg of G-CSF (Lenograstim) daily over a period of 5 days. Daily blood sampling and repeated BM sampling showed that FL concentration before mobilization was negatively correlated to the absolute number of BM CD34(+) cells, but also to the number of G-CSF-mobilized CD34(+) cells on days 3-5 of treatment.

Renal anemia induced by chronic ingestion of depleted uranium in rats.

Kidney disease is a frequent consequence of heavy metal exposure and renal anemia occurs secondarily to the progression of kidney deterioration into chronic disease. In contrast, little is known about effects on kidney of chronic exposure to low levels of depleted uranium (DU). Study was performed with rats exposed to DU at 40 mg/l by chronic ingestion during 9 months.

Use of flt3 ligand to evaluate residual hematopoiesis after heterogeneous irradiation in mice.

We evaluated the possibility of using plasma Flt3 ligand (FL) concentration as a biological indicator of bone marrow function after heterogeneous irradiation. Mice were irradiated with 4, 7.5 or 11 Gy with 25, 50, 75 or 100% of the bone marrow in the field of irradiation.

Kinetics of plasma FLT3 ligand concentration in hematopoietic stem cell transplanted patients.

The present study aimed to follow-up variations in plasma Flt3 ligand (FL) concentration after hematopoietic stem cell transplantation and to compare the influence of conditioning regimens on variations in FL concentration. Ten patients undergoing a conditioning regimen, including BEAM, cyclophosphamide (Cy) + total body irradiation or Cy + anti-thymocyte globulins (ATG), which was then followed by hematopoietic stem cell transplantation, were studied. Plasma FL concentrations, white blood cell (WBC) expression of both FL mRNA and the membrane-bound form of FL were carried out at different times post-treatment.

Comparison of autologous cell therapy and granulocyte-colony stimulating factor (G-CSF) injection vs. G-CSF injection alone for the treatment of acute radiation syndrome in a non-human primate model.

Purpose: To compare the efficacy of autologous cell therapy after irradiation combined with granulocyte-colony stimulating factor (G-CSF) injections with G-CSF treatment alone in a heterogeneous model of irradiation representative of an accidental situation.

Material And Methods: Non-human primates were irradiated at 8.7 Gy whole-body dose with the right arm shielded to receive 4.