Strain-dependent Damage in Mouse Lung After Carbon Ion Irradiation
Strain-dependent Damage in Mouse Lung After Carbon Ion Irradiation
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DOI：
10.1016/j.ijrobp.2012.02.013
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发表时间：
2012-09-01
影响因子：
7
通讯作者：
Imai, Takashi
中科院分区：
文献类型：
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作者：
Moritake, Takashi;Fujita, Hidetoshi;Imai, Takashi
目的：为了检查是否有内在因素导致了对碳离子（C-离子）照射的肺发病率的差异，并确定在肺中应变依赖性不良反应中起关键作用的分子。方法和材料：三种雌性小鼠用C-离子束在胸部局部照射C3 H/He Slc、C57 BL/6 J Jms Slc和A/J Jms Slc（290 MeV/n，在6 cm展开的布拉格峰中）或用Cs-137 γ射线作为参考束。我们进行了生存分析和组织学检查的肺苏木精-伊红和Masson的三色染色。此外，我们进行了免疫组化染色透明质酸（HA），CD 44，和Mac 3和基因expression.Results：小鼠的生存数据显示了10戈伊的C-离子照射后株间方差。高剂量（12.5戈伊）C离子照射后，C3 H/He细胞的中位生存时间明显缩短。组织学检查显示10戈伊C离子照射后，C3 H/He出现早期出血性肺炎，C57 BL/6 J出现晚期局灶性纤维化病变。C57 BL/6 J和A/J小鼠在10戈伊C离子照射后168天出现明显胸腔积液。在三种小鼠品系的照射肺组织的微阵列分析确定了生长分化因子15（Gdf 15），它调节巨噬细胞的功能，和透明质酸合酶1（Has 1），这在HA代谢中发挥作用的差异表达变化。免疫组化结果表明，CD 44阳性细胞的数量，HA积累的替代标志物，和Mac 3阳性细胞，在照射肺巨噬细胞浸润的标志物，在早期phase.Conclusions三个小鼠品系之间的显着变化：这项研究表明，在小鼠中的应变依赖性差异反应C-离子胸部照射。我们的研究结果确定了可能与C离子照射后早期出血性肺炎菌株间差异有关的候选分子。(C)2012 Elsevier Inc.
Purpose: To examine whether inherent factors produce differences in lung morbidity in response to carbon ion (C-ion) irradiation, and to identify the molecules that have a key role in strain-dependent adverse effects in the lung.Methods and Materials: Three strains of female mice (C3H/He Slc, C57BL/6J Jms Slc, and A/J Jms Slc) were locally irradiated in the thorax with either C-ion beams (290 MeV/n, in 6 cm spread-out Bragg peak) or with Cs-137 gamma-rays as a reference beam. We performed survival assays and histologic examination of the lung with hematoxylin-eosin and Masson's trichrome staining. In addition, we performed immunohistochemical staining for hyaluronic acid (HA), CD44, and Mac3 and assayed for gene expression.Results: The survival data in mice showed a between-strain variance after C-ion irradiation with 10 Gy. The median survival time of C3H/He was significantly shortened after C-ion irradiation at the higher dose of 12.5 Gy. Histologic examination revealed early-phase hemorrhagic pneumonitis in C3H/He and late-phase focal fibrotic lesions in C57BL/6J after C-ion irradiation with 10 Gy. Pleural effusion was apparent in C57BL/6J and A/J mice, 168 days after C-ion irradiation with 10 Gy. Microarray analysis of irradiated lung tissue in the three mouse strains identified differential expression changes in growth differentiation factor 15 (Gdf15), which regulates macrophage function, and hyaluronan synthase 1 (Has1), which plays a role in HA metabolism. Immunohistochemistry showed that the number of CD44-positive cells, a surrogate marker for HA accumulation, and Mac3-positive cells, a marker for macrophage infiltration in irradiated lung, varied significantly among the three mouse strains during the early phase.Conclusions: This study demonstrated a strain-dependent differential response in mice to C-ion thoracic irradiation. Our findings identified candidate molecules that could be implicated in the between-strain variance to early hemorrhagic pneumonitis after C-ion irradiation. (C) 2012 Elsevier Inc.