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: 6543532
• 负责人: Ray Lloyd
• 金额: $ 25.54万
• 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/6543532
• 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（由申请人提供）：癌症风险和公众对暴露于α发射放射性核素（如镅、钚、钍、镭等）的相关关注是众所周知的。目前的保护模式主要基于统计假设，几乎没有生物数据。我们已经开发了符合实验数据的生物动力学模型，现在将在人体中测试这些模型，并确定钚在俄罗斯核工作人员现有的存档骨骼组织中的定位、分布和剂量测定。实验和人体数据将被用来扩展我们目前的生物动力学，剂量和风险模型的人。其目标是：1）确定犬材料中组织和细胞的沉积和局部辐射剂量，作为暴露于钚后时间的函数。将使用中子诱导（NIAR）和常规放射自显影方法。将构建生物动力学模型。2)为钚照射制定一个“年龄质量因素”。我们的研究表明，重要的年龄依赖性的核素摄取，保留和随后的风险的生物决定因素。这些包括骨生长、骨重建和造血及血管形成。3)利用NIAR技术测定了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。材料将从美国和更多高度暴露的俄罗斯工人的档案中获得。4)将工人暴露和职业和临床史与存档的人体骨骼样本（美国和俄罗斯）中239-Pu的定位和分布相关联。确定晚期慢性病对器官系统中钚再分配的影响。这些数据可能会大大改变目前的剂量测定和风险模型。5)确定241-Am与239-Pu的组织定位。这将提供对有转化风险的细胞的深入了解，以及关于241-Am的更多生物动力学信息，241-Am是核技术的重要副产品。6)目标3和目标4的数据以及人体数据将用于检验钚的α辐射人体模型。模型中的空白将用目标1、2和5的实验研究数据填补。7)建立α诱导肿瘤的一般风险模型。为此，关于镭的人体和实验研究数据将用作外推到其他α放射核素的基础。