Wound trauma alters ionizing radiation dose assessment
Wound trauma alters ionizing radiation dose assessment
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DOI：
10.1186/2045-3701-2-20
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发表时间：
2012-06-11
影响因子：
7.5
通讯作者：
Ledney, G. David
中科院分区：
文献类型：
--
作者：
Kiang, Juliann G.;Garrison, Bradley R.;Ledney, G. David
背景：全身创伤。-辐射(辐射复合损伤，RCI)会增加死亡率。创伤导致的辐射死亡率增加是由诱导型一氧化氮合酶途径的持续激活、细胞因子稳态的持续改变以及对细菌感染的易感性增加所触发的。在这些因素中，细胞因子和其他生物标志物已被用于辐射剂量和损伤的生物剂量评估和评估。因此，创伤可能会使生物剂量学评估复杂化。结果：在这份报告中，这种混杂的影响被解决了。小鼠接受Co-60伽马光子照射，然后进行皮肤损伤。伤口创伤加剧了辐射导致的死亡、体重减轻和伤口愈合。分析骨髓细胞和外周血单个核细胞(PBMC)的DNA损伤情况、血液学和细胞因子谱的变化以及基本临床体征。早期生物标志物(RCI后1d)与单纯照射相比，包括骨髓细胞Survivin表达显著降低，LIN(+)骨髓细胞伽马-H_2AX形成增加，血液中IL-1β、IL-6、IL-8和G-CSF浓度增加，PBMC中γ-H_2AX形成减少，脾细胞、淋巴细胞和中性粒细胞数量减少。中间生物标志物(RCI后7-10d)包括持续减少PBMC中γ-H_2AX的形成和增加血液中IL-1β、IL-6、IL-8和G-CSF的浓度。术后临床体征表现为用水量增加，体重减轻，创面愈合率和存活率下降。晚期临床体征(RCI后30d)包括存活率和创面愈合不良。结论：创伤改变、电离辐射剂量评估和抑制这些反应的药物等混杂因素可能对放射合并伤有治疗作用，并降低相关死亡率。
Background: Wounding following whole-body.-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.Results: In this report, such confounding effects were addressed. Mice were given Co-60 gamma-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 gamma-H2AX formation in Lin(+) bone marrow cells, enhanced increases in IL-1 beta, IL-6, IL-8, and G-CSF concentrations in blood, and concomitant decreases in gamma-H2AX formation in PBMCs and decreases in numbers of splenocytes, lymphocytes, and neutrophils. Intermediate biomarkers (7 - 10 d after RCI) included continuously decreased gamma-H2AX formation in PBMC and enhanced increases in IL-1 beta, 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.Conclusion: Results 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.