Center for Biophysical Assessment and Risk Management Following Irradiation

我们中心的中心主题是继续改进现有的风险预测方法和 以改善辐射的副作用。我们的风险和干预评估将基于体检 剂量、宿主细胞因子平衡和遗传毒性。我们将强调理解和减轻与辐射相关的 发炎。在该中心，我们将注意力转向辐射恐怖主义的不同方面，但 强调暴露于不会立即致命的固体器官的损害(例如，低剂量慢性 暴露、吸入暴露)。我们预计，在供资期间结束时，我们将完善实物 受害者的生物剂量标记物，以及重要的减肥剂。我们项目的假设是 得到大量初步数据的支持，使我们对在具有挑战性的搜索中取得成功抱有很高的期望 寻求对策。该中心还将通过培训和指导活动发展壮大。 项目1和2涉及暴露类型(吸入与外部低/高LET)和#年的缓释剂。 坚固的器官，重点是肺、肠和皮肤软组织。我们有初步数据显示 几种缓解剂，包括在小鼠身上的长期数据和在癌症患者中的阳性临床试验。 项目3的特点是在牙釉质(或骨)的碳酸盐中使用自旋陷阱，并在 头发和指甲的硫酸盐，与胶片剂量测定使用硝酸银的方式很相似。被困住的自转 牙科碳酸盐是永久性的，通过活体非侵入性电子自旋共振进行测量。 项目4和5的特点是剂量测定和对全身的遗传毒性(使用立即读数 网织红细胞微核)和皮肤组织(使用角质形成细胞微核和DNA链断裂 复合检测)。一种能够强有力地测试试剂和骨髓细胞亚群的骨髓生物反应器将 也可与低字母和高字母连用。 项目6研究了一种产生局部损害的新癌症疗法，为 肺放射敏感性的定量分析，因此是在人体模型中测试缓解剂的手段。 生物统计核心将协助所有项目的实验设计/数据分析，并提供先进的 分析以确定重要的标志物，并提出整合宿主的治疗建议 敏感性测量(项目1、2)与物理剂量(项目3)和遗传毒性(项目4、5)。

The central theme of our Center is the continued improvement of existing approaches for predicting risk and for ameliorating the side effects of radiation. Our risk and intervention estimators will be based on physical dose, host cytokine balance, and genotoxicity. We will emphasize understanding and mitigating radiationrelated inflammation. In the Center, we direct attention to different aspects of radiation terrorism, but emphasize damage to solid organs at exposures that are not immediately lethal (e.g. low dose chronic exposures, inhalational exposure). We expect that, at the end of the funded period, we will refine physical and biodosimetric markers for victims and, importantly, mitigating agents. Our projects' hypotheses are supported by substantial preliminary data, giving us a high expectation of success in the challenging search for countermeasures. The Center wil also grow through training and mentoring activities. Projects 1 and 2 deal with exposure types (inhalation vs. external low/high LET) and mitigation agents in solid organs, with emphasis on lung, bowel, and cutaneous soft tissues. We have preliminary data on several mitigating agents, including long-term data in mice and positive clinical trials in cancer patients. Project 3 features a technology that uses the spin traps in the carbonate of tooth enamel (or bone) and in sulfate of hair and nails, much in the same way as film dosimetry uses silver nitrate. The trapped spins in dental carbonate are permanent and are measured by in vivo non-invasive electron spin resonance. Projects 4 and 5 feature dosimetry and genotoxicity to the whole body (using an immediate readout on reticulocyte micronuclei) and cutaneous tissues (using keratinocyte micronucei and DNA strand break complex detection). A marrow bioreactor that can powerfully test agents and marrow cell subpopulations will also be used with low and high LET. Project 6 investigates a new cancer therapy that produces localized damage, offering the opportunity for quantitative analysis of lung radiosensitivity and thus a means to test mitigating agents in a human model. Biostatistics Core will assist with experimental design/data analysis in all projects and provide advanced analysis to identify significant markers and make treatment recommendations that integrate the host susceptibility measurements (Projects 1, 2) with physical dose (Project 3) and genotoxicity (Projects 4, 5).