Wound trauma alters ionizing radiation dose assessment

Abstract

BackgroundWounding following whole-body γ-irradiation (radiation combined injury, RCI) increases mortality. Wounding-induced increases in radiation mortality are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to bacterial infection. Among these factors, cytokines along with other biomarkers have been adopted for biodosimetric evaluation and assessment of radiation dose and injury. Therefore, wounding could complicate biodosimetric assessments.ResultsIn this report, such confounding effects were addressed. Mice were given 60Co γ-photon radiation followed by skin wounding. Wound trauma exacerbated radiation-induced mortality, body-weight loss, and wound healing. Analyses of DNA damage in bone-marrow cells and peripheral blood mononuclear cells (PBMCs), changes in hematology and cytokine profiles, and fundamental clinical signs were evaluated. Early biomarkers (1 d after RCI) vs. irradiation alone included significant decreases in survivin expression in bone marrow cells, enhanced increases in γ-H2AX formation in Lin+ bone marrow cells, enhanced increases in IL-1β, IL-6, IL-8, and G-CSF concentrations in blood, and concomitant decreases in γ-H2AX formation in PBMCs and decreases in numbers of splenocytes, lymphocytes, and neutrophils. Intermediate biomarkers (7 – 10 d after RCI) included continuously decreased γ-H2AX formation in PBMC and enhanced increases in IL-1β, IL-6, IL-8, and G-CSF concentrations in blood. The clinical signs evaluated after RCI were increased water consumption, decreased body weight, and decreased wound healing rate and survival rate. Late clinical signs (30 d after RCI) included poor survival and wound healing.ConclusionResults suggest that confounding factors such as wounding alters ionizing radiation dose assessment and agents inhibiting these responses may prove therapeutic for radiation combined injury and reduce related mortality.

Pegfilgrastim Administered in an Abbreviated Schedule, Significantly Improved Neutrophil Recovery after High-Dose Radiation-Induced Myelosuppression in Rhesus Macaques

“…This warrants further exploration. Radiation alone and combined injury significantly reduced platelet counts (1,2). At day 30 after irradiation alone or combined injury, surviving mice still displayed significantly low platelet counts (Fig.…”

Wound Trauma Increases Radiation-Induced Mortality by Activation of iNOS Pathway and Elevation of Cytokine Concentrations and Bacterial Infection

“…Radiation alone and combined injury significantly reduced RBC counts, hemoglobin levels and hematocrit values (1,2). At day 30 after irradiation alone and combined injury, surviving mice still displayed significantly low RBC counts, hemoglobin levels and hematocrit values (Fig.…”

Ciprofloxacin Therapy Results in Mitigation of ATP Loss after Irradiation Combined with Wound Trauma: Preservation of Pyruvate Dehydrogenase and Inhibition of Pyruvate Dehydrogenase Kinase 1

“…However, skin wound trauma after irradiation accelerates the onset of radiation-induced mortality by 3-8 days depending on the radiation dose, indicating the presence of the gastrointestinal syndrome (5, 6). The time course of reduction in survival is also correlated with body weight loss (22), suggesting this may be due to either: 1. reduction of food intake; 2. impairment of GI function; or 3. the combination of these two factors, leading to lack of energy to maintain the body weight. ATP is the main energy form for a variety of cellular processes, including DNA, RNA and protein synthesis, maintenance of the cytoskeleton, signaling, ion transport and repair.…”

“…As a result, the homeostasis between the enzymatic activities of PDH and PDK remains critical to cell integrity for survival. It appears that combined injury disrupted the metabolic homeostasis, which may in turn have led to diminished ATP production, thus contributing to the combined injury-induced blood cell depletion (22).…”