A Further Comparison of Pathologies after Thoracic Irradiation among Different Mouse Strains: Finding the Best Preclinical Model for Evaluating Therapies Directed Against Radiation-Induced Lung Damage
A Further Comparison of Pathologies after Thoracic Irradiation among Different Mouse Strains: Finding the Best Preclinical Model for Evaluating Therapies Directed Against Radiation-Induced Lung Damage
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DOI：
10.1667/rr2421.1
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发表时间：
2011-04-01
影响因子：
3.4
通讯作者：
Down, Julian D.
中科院分区：
文献类型：
--
作者：
Jackson, Isabel L.;Vujaskovic, Zeljko;Down, Julian D.
不同品系小鼠胸部照射后病理学的进一步比较：为评估针对辐射诱导的肺损伤的治疗寻找最佳临床前模型。辐射。研究报告175,510-518(2011)。在局部和全身辐射暴露中，人的肺是最敏感和最关键的组织之一，它是辐射对策计划内评估缓解治疗的积极临床前研究的对象。我们之前的研究比较了C57BL/6、CBA和C57L小鼠在全胸照射后的情况，指出了迟发性胸腔积液的问题，这些问题阻碍了C57BL/6小鼠肺损伤的充分发展，并表明CBA和C57L品系更有利于建立人类肺损伤的模型(Jackson等，Radiat。2010年10月20日第173号决议)。我们将这些比较扩展到其他三个品系的小鼠(BALB/c、C57BR/J和A/J小鼠)，这些小鼠受到10、12.5或15Gy射线的照射。根据大体病理、组织学和显微CT检查，这些小鼠大多无法存活前6个月，表现为肺损伤和胸腔积液的混合体。病因不明的压迫性胸腔积液的独立和不同的发展代表了对这些菌株的担忧，因为它们可能不满足临床前批准用于人类使用的医学对策(例如放射缓释剂)的要求。因此，到目前为止，在针对这些病理学研究的各种不同的小鼠品系中，似乎只有三个品系(CBA、C3H和C57L)在表现出完全由放射性肺炎引起的早期肺功能障碍以及进一步评估放射防护和缓解治疗方面是可取的。C57L小鼠尤其相关，因为它们在较低的辐射剂量下表现出明显的肺损伤，这更接近于对人类的预测。2011年由辐射研究学会提供
Jackson, I. L., Vujaskovic, Z. and Down, J. D. A Further Comparison of Pathologies after Thoracic Irradiation among Different Mouse Strains: Finding the Best Preclinical Model for Evaluating Therapies Directed Against Radiation-Induced Lung Damage. Radiat. Res. 175, 510-518 (2011).The human lung is among the most sensitive and critical tissues of concern in localized and systemic radiation exposures, and it is a subject of active preclinical research for evaluating mitigating therapies within the radiation countermeasures program. Our previous study comparing C57BL/6, CBA and C57L mice after whole-thorax irradiation pointed to the problems of late pleural effusions that prevented the full development of lung injury in C57BL/6 mice and suggested that the CBA and C57L strains are more favorable for modeling lung injury in humans (Jackson et al., Radiat. Res. 173, 10-20, 2010). We extended these comparisons to include three other mouse strains (BALB/c, C57BR/J and A/J mice) irradiated with 10, 12.5 or 15 Gy. Most of these mice were unable to survive the first 6 months and presented with a mixture of lung injury and pleural effusions as determined from gross pathology, histology and micro-CT. The independent and varying development of compressive pleural effusions of ill-defined etiology represents a concern for these strains in that they may not satisfy the preclinical requirements for approval of medical countermeasures (e.g. radiation mitigators) for human use. Thus, among the various different mouse strains studied so far for these pathologies, only three (CBA, C3H and C57L) appear to be desirable in exhibiting an early wave of pulmonary dysfunction attributed exclusively to radiation pneumonitis and for further assessment of radioprotective and mitigating therapies. C57L mice are particularly relevant in that they show significant lung damage at lower radiation doses that are closer to what is predicted for humans. 2011 by Radiation Research Society