New Biological Indicators to Evaluate and Monitor Radiation-Induced Damage: An Accident Case Report

Bertho, Jean-Marc; Roy, Laurence; Souidi, Maâmar; Benderitter, Marc; Guéguen, Yann; Lataillade, Jean‐Jacques; Prat, Marie; Fagot, T.; Revel, Thierry de; Gourmelon, P.

doi:10.1667/rr1259.1

Cited by 63 publications

(24 citation statements)

References 29 publications

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“…Peg-G-CSF is known to initiate proliferation and differentiation of myeloid progenitors into mature granulocytes and to induce hematopoietic stem cell mobilization from the bone marrow into the bloodstream, making it effective for recovery from infection (13, 14) and wound healing (15). Peg-G-CSF, when combined with stem cell factors and erythropoietin, was used to treat a technician, who was exposed to gamma radiation (16). From our study, we postulate further, that peg-G-CSF mobilizes hematopoietic progenitor cells in addition to myeloid cells to peripheral blood to mitigate the blood cell depletion (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…It is involved in infection recovery (13, 14) and wound healing (15). Peg-G-CSF, when combined with stem cell factors (SCF) and erythropoietin (EPO), was successfully used in the rescue of a hospital technician who had accidentally entered a 60 Co irradiation therapy room and received a 4.5 Gy dose (16). Other known radiological accidents where victims received G-CSF treatments have been reported as well (17).…”

Section: Introductionmentioning

confidence: 99%

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Combined Therapy of Pegylated G-CSF and Alxn4100TPO Improves Survival and Mitigates Acute Radiation Syndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma

et al. 2017

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Exposure to ionizing radiation alone or combined with traumatic tissue injury is a crucial life-threatening factor in nuclear and radiological incidents. Radiation injuries occur at the molecular, cellular, tissue and systemic levels; their mechanisms, however, remain largely unclear. Exposure to radiation combined with skin wounding, bacterial infection or burns results in greater mortality than radiation exposure alone in dogs, pigs, rats, guinea pigs and mice. In the current study we observed that B6D2F1/J female mice exposed to 60Co gamma-photon radiation followed by 15% total-body-surface-area skin wounds experienced an increment of 25% higher mortality over a 30-day observation period compared to those subjected to radiation alone. Radiation exposure delayed wound healing by approximately 14 days. On day 30 post-injury, bone marrow and ileum in animals from both groups (radiation alone or combined injury) still displayed low cellularity and structural damage. White blood cell counts, e.g., neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets, still remained very low in surviving irradiated alone animals, whereas only the lymphocyte count was low in surviving combined injury animals. Likewise, in surviving animals from radiation alone and combined injury groups, the RBCs, hemoglobin, hematocrit and platelets remained low. We observed, that animals treated with both pegylated G-CSF (a cytokine for neutrophil maturation and mobilization) and Alxn4100TPO (a thrombopoietin receptor agonist) at 4 h postirradiation, a 95% survival (vehicle: 60%) over the 30-day period, along with mitigated body-weight loss and significantly reduced acute radiation syndrome. In animals that received combined treatment of radiation and injury that received pegylated G-CSF and Alxn4100TPO, survival was increased from 35% to 55%, but did not accelerate wound healing. Hematopoiesis and ileum showed significant improvement in animals from both groups (irradiation alone and combined injury) when treated with pegylated G-CSF and Alxn4100TPO. Treatment with pegylated G-CSF alone increased survival after irradiation alone and combined injury by 33% and 15%, respectively, and further delayed wound healing, but increased WBC, RBC and platelet counts after irradiation alone, and only RBCs and platelets after combined injury. Treatment with Alxn4100TPO alone increased survival after both irradiation alone and combined injury by 4 and 23%, respectively, and delayed wound healing after combined injury, but increased RBCs, hemoglobin concentrations, hematocrit values and platelets after irradiation alone and only platelets after combined injury. Taken together, the results suggest that combined treatment with pegylated G-CSF and Alxn4100TPO is effective for mitigating effects of both radiation alone and in combination with injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combined Therapy of Pegylated G-CSF and Alxn4100TPO Improves Survival and Mitigates Acute Radiation Syndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma

et al. 2017

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“…This is independently of the inflammatory or nutritional status of patients with various conditions including short bowel syndrome, bowel ischaemia, Coeliac disease, as well as following intestinal transplantation, cytoreductive therapy and therapeutic or accidental irradiation [1][2][3][22][23][24]. A rapidly available result of citrulline in daily clinical practice would enable the clinician to precisely monitor the course of intestinal dysfunction and would offer him or her a tool to manage a patient with signs of intestinal failure which is also relevant in premature children [20].…”

Section: Biological Variation During Myeloablative Therapymentioning

confidence: 99%

Plasma citrulline measurement using UPLC tandem mass-spectrometry to determine small intestinal enterocyte pathology

Demacker

Beijers

Daal

et al. 2009

Journal of Chromatography B

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“…Their data also suggested that the FLt3L concentration analysis plus CBC analysis may serve as a method for rapid evaluation of radiation injury. This analysis was also applied to another accident victim [15]. The long-term results from a fractionated human radiation study [13] further support the notion that at least FLt3L may respond to radiation at a protracted dose rate.…”

Section: Discussionmentioning

confidence: 64%

“…This group also showed that the overall amount of Flt3L correlated directly with the cumulative radiation dose and the proportion of irradiated bone marrow in humans during a fractionated-radiation therapy trial [13]. The Flt3L assay was also used to demonstrate the severity of the bone marrow aplasia after two different radiation accidents [14,15]. Thus, for biodosimetry after acute irradiation exposure, Flt3L has been validated as a marker in mice, NHPs and humans.…”

Section: Introductionmentioning

confidence: 96%

Radiation Dose-Rate Effects on Select Biomarkers in a Mouse Total-Body Irradiation Model

Hegge¹,

Kin²

2017

RadJ

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Abstract. In the event of acute radiation exposure, absorbed dose may be unknown and biodosimetry tools are needed by first responders to properly triage patients. We evaluated two protein markers -FMS-related tyrosine kinase 3 ligand (Flt3L) and granulocyte colony-stimulating factor (G-CSF) -that are known to be elevated after an acute radiation exposure, as well as total white blood cell (WBC) count changes pre-and post-irradiation at different dose-rates. Female B6D2F1 mice were divided into one sham-irradiated control group and four total-body irradiated groups. Experimental groups received a total dose of 8 Gy of 60 Co gamma photon irradiation at four dose-rates: 0.04, 0.15, 0.30, and 0.47 Gy min -1 . Blood samples from mice were collected at 24 and 48 hours post-exposure for WBC and protein biomarkers (Flt3L and G-CSF). Flt3L values at all dose-rates except 0.15 were significantly elevated from controls but not each other. The G-CSF levels in mouse groups of 0.47 Gy min -1 and 0.04 Gy min -1 were significantly different from controls, and 0.15 Gy min-1 significantly differed from 0.47 Gy min -1 . WBC changes from baseline showed that all experimental groups were significantly lower than controls, and additionally the 0.04 Gy min -1 group was significantly lower than the 0.30 Gy min -1 group. Though more research is needed, it would appear that at the fixed dose, dose-rates, and time points chosen herein may not be particularly strong or show predictable differences in the selected biomarker expression levels.

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New Biological Indicators to Evaluate and Monitor Radiation-Induced Damage: An Accident Case Report

Cited by 63 publications

References 29 publications

Combined Therapy of Pegylated G-CSF and Alxn4100TPO Improves Survival and Mitigates Acute Radiation Syndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma

Combined Therapy of Pegylated G-CSF and Alxn4100TPO Improves Survival and Mitigates Acute Radiation Syndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma

Plasma citrulline measurement using UPLC tandem mass-spectrometry to determine small intestinal enterocyte pathology

Radiation Dose-Rate Effects on Select Biomarkers in a Mouse Total-Body Irradiation Model

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