Acute gastrointestinal syndrome in high-dose irradiated mice.

Acute gastrointestinal syndrome in high-dose irradiated mice.
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DOI:
10.1097/hp.0b013e318266ee13
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发表时间:
2012-10
期刊:
影响因子:
2.2
通讯作者:
MacVittie TJ
MacVittie TJ
中科院分区:
医学4区
文献类型:
--
作者:
Booth C;Tudor G;Tudor J;Katz BP;MacVittie TJ

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胃肠道系统对高剂量急性辐射的反应的最详细报告主要集中在理解组织病理学上。但是,为了在动物规则标准下实现医学对策评估,有必要建立一个可靠的模型,在这种模型中,辐射剂量与肠道辐射综合征的发生率,时间和严重程度与组织病理学建立并相关。尽管已经发表了许多死亡率研究,但他们使用了各种小鼠菌株,年龄,放射源和饲养条件,所有这些都会影响剂量反应。此外,很明显,骨髓照射和支撑性护理的水平会影响终点。为了创建强大的基线数据,我们已经在成年雄性小鼠中产生了剂量反应数据,维持在相同的条件下,并暴露于总体或部分体体照射。部分体型的照射包括广泛的(40%)和最小(5%)骨髓间隔模型,后者旨在与已建立的灵长类动物模型相关,并允许评估任何医学对策对所有三种主要辐射综合症(肠道,肠道,,肠道,,,,,,肠道)的影响幸存的小鼠中的骨髓和肺)。各种模型中描述了致命剂量(LD30,LD50和LD70)数据,以及肠菌群的影响和对支持护理的反应。还描述了与腹泻严重程度和组织病理学的相关性。该数据可用于帮助设计良好的实验室实践(GLP)符合动物规则研究,这些研究反映了意外辐射暴露后的状况。
The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data we have generated dose response data in adult male mice, maintained under identical conditions, and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow and lung) in the surviving mice. Lethal dose (LD30, LD50 and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. This data can be used to aid the design of good laboratory practice (GLP) compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure.
DOI: 10.1097/hp.0b013e31825f75a7
发表时间: 2012-10
期刊: Health physics
影响因子: 2.2
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Farese AM;Cohen MV;Katz BP;Smith CP;Jackson W 3rd;Cohen DM;MacVittie TJ
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