POPULATION RISK MODEL FOR ALPHA-INDUCED BONE NEOPLASMS

描述（由申请人提供）：暴露于释放α的放射性核素（如镅、钚、钍、镭等）的癌症风险和相关的公众关注是公认的。目前的保护模型主要基于统计假设，很少有生物学数据。我们已经开发出符合实验数据的生物动力学模型，现在将在人体中测试这些模型，并确定钚在俄罗斯核工人骨骼组织中的位置、分布和剂量。实验和人体数据将用于将我们目前的生物动力学、剂量学和风险模型扩展到人类。目的是：1)确定暴露于钚后犬材料中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。将构建生物动力学模型。2)建立钚暴露的“年龄质量因子”。我们的研究证明了核素摄取、保留和随后风险的重要年龄依赖性生物决定因素。这些包括骨生长、骨重塑、造血和血管形成。3)利用NIAR测定239-Pu在人体组织中的定位、分布和对组织细胞的辐射剂量。材料将从美国和更多的俄罗斯工人的档案中获得。4)将工人暴露、职业和临床病史与存档的人类骨骼样本中239-Pu的定位和分布联系起来（美国和俄罗斯）。目的：探讨晚期慢性疾病对各脏器系统间嘌呤再分布的影响。这些数据可能会大大改变目前的剂量学和风险模型。5)确定241-Am与239-Pu的组织定位。这将提供对处于转化风险中的细胞的深入了解，并提供更多关于241-Am的生物动力学信息，这是核技术的重要副产品。6)目标3和目标4的数据和人体数据将用于测试钚暴露于α的人体模型。模型中的空白将由目标1、目标2和目标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，关于镭的人体研究和实验研究的数据将作为推断其他α -发射核素的基础。

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.