Center for Biophysical Assessment and Risk Management

描述（由申请人提供）：我们中心的中心主题是继续改进现有的方法来预测风险和改善辐射的副作用。我们的风险和干预估计将基于物理剂量，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有关的炎症。在该中心，我们关注辐射恐怖主义的不同方面，但强调不会立即致命的照射（例如低剂量慢性照射，吸入照射）对实体器官的损害。我们预计，在供资期结束时，我们将改进受害者的物理和生物剂量测定标记，重要的是改进缓解剂。我们的项目假设得到了大量初步数据的支持，这使我们对成功寻找具有挑战性的对策寄予厚望。该中心还将通过培训和辅导活动发展壮大。项目1和2涉及实体器官中的接触类型（吸入与外部低/高LET）和缓解剂，重点是肺、肠和皮肤软组织。我们有几种缓解药物的初步数据，包括小鼠的长期数据和癌症患者的阳性临床试验。项目3的特点是在牙釉质（或骨骼）的碳酸盐和头发和指甲的硫酸盐中使用自旋陷阱，这与胶片剂量测定法使用硝酸银的方式非常相似。牙科碳酸盐中的捕获自旋是永久性的，并且通过体内非侵入性电子自旋共振来测量。项目4和5的特点是对全身（使用网织红细胞微核的即时读数）和皮肤组织（使用角质形成细胞微核和DNA链断裂复合物检测）的剂量测定和遗传毒性。一个骨髓生物反应器，可以有力地测试代理和骨髓细胞亚群也将使用低和高LET。生物统计学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，并提出治疗建议，将宿主易感性测量（项目1，2）与物理剂量（项目3）和遗传毒性（项目4，5）相结合。

DESCRIPTION (provided by applicant): 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 radiation-related 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 will 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 micronuclei 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. 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).