POPULATION RISK MODEL FOR ALPHA-INDUCED BONE NEOPLASMS

ALPHA 引起的骨肿瘤的人群风险模型

• 批准号: 6792661
• 负责人: Ray Lloyd
• 金额: $ 24.23万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6792661
• 关键词: age group; americium; animal tissue; autoradiography; biological models; bone development; bone neoplasms; cancer risk; disease /disorder onset; environmental exposure; hematopoiesis; human data; human population study; human tissue; image processing; model design /development; morphometry; neoplastic transformation; neutron radiation; plutonium; radiation dosage; radiation related neoplasm /cancer; radionuclides

DESCRIPTION (provided by applicant): The cancer risk and associated public concern with exposures to alpha-emitting radionuclides, such as americium, plutonium, thorium, radium and others is well recognized. Current protection models are based largely on statistical assumptions with little biological data. We have developed biokinetic models that fit the experimental data, and will now test these models in the human and determine the localization, distribution and dosimetry of plutonium in archived skeletal tissues now available from Russian nuclear workers. Both experimental and human data will be used to extend our current biokinetic, dosimetric and risk models to the human. The aims are: 1) To determine in canine materials the deposition and local radiation doses to tissues and cells as a function of time after exposure to plutonium. Neutron induced (NIAR) and conventional autoradiographic methods will be used. A biokinetic model will be constructed. 2) To develop an "age quality factor" for exposures to plutonium. Our studies demonstrate important age-dependent biological determinants of nuclide uptake, retention and subsequent risk. These include bone growth, bone remodeling and hematopoiesis and vascularization. 3) The localization, distribution and radiation doses to tissues and cells from 239-Pu will be determined in human tissues using NIAR. Materials will be obtained from archives of both U.S. and more highly exposed Russian workers. 4) To correlate worker exposure and occupational and clinical history with the localization and distribution of 239-Pu in archived human skeletal samples (U.S. and Russian). To determine the influence of late chronic diseases on the redistribution of Pu among organ systems. These data may substantially alter current dosimetry and risk models. 5) Determine the tissue localization of 241-Am vs. 239-Pu. This will provide insights into the cells at risk for transformation and also more biokinetic information on 241-Am, an important byproduct of nuclear technologies. 6) Data from aims 3 and 4 with human data will be used to test human models of alpha exposure from plutonium. Gaps in the model will be filled with data from experimental studies from Aims 1,2 and 5. 7) To develop a general risk model for alpha-induced neoplasms. For this, data in human and experimental studies on radium will be used as a basis for extrapolation to other alpha-emitting nuclides.

描述(由申请者提供)：暴露于放射阿尔法放射性核素，如Am、Pu、Th、Re和其他放射性核素的致癌风险和相关的公众关注是公认的。目前的保护模型很大程度上是基于统计假设，几乎没有生物学数据。我们已经开发出符合实验数据的生物动力学模型，现在将在人体上测试这些模型，并确定钚在存档的骨骼组织中的定位、分布和剂量学，目前可从俄罗斯核工作者那里获得。实验和人体数据都将被用来将我们目前的生物动力学、剂量学和风险模型扩展到人类。其目的是：1)确定暴露于钚后对组织和细胞的沉积和局部辐射剂量随时间的变化。将使用中子诱导(NIAR)和传统的放射自显影方法。将构建一个生物动力学模型。2)制定暴露于钚的“年龄质量因素”。我们的研究表明，核素摄取、滞留和后续风险的重要生物学决定因素与年龄有关。这些包括骨生长、骨重建、造血和血管形成。3)~(239)Pu在人体组织中的定位、分布和对组织和细胞的辐射剂量将用NIAR确定。材料将从美国和更多暴露在危险中的俄罗斯工人的档案中获得。4)将工人暴露、职业和临床病史与239-Pu在存档的人类骨骼样本(美国和俄罗斯)中的定位和分布联系起来。目的：探讨晚期慢性病对钚在各器官系统中再分配的影响。这些数据可能会极大地改变当前的剂量测定和风险模型。5)确定~(241)Am与~(239)Pu的组织定位。这将提供对处于转化风险的细胞的洞察，并提供更多关于核技术的重要副产品241-Am的生物动力学信息。6)来自AIMS 3和AIMS 4的数据以及人体数据将被用来测试从钚中暴露的阿尔法人体模型。模型中的空白将用来自目标1、2和5.7的实验研究的数据来填补，以开发一个阿尔法诱发肿瘤的一般风险模型。为此，人体和实验研究中的数据将被用来作为推断其他阿尔法发射核素的基础。