POPULATION RISK MODEL FOR ALPHA-INDUCED BONE NEOPLASMS

描述暴露于趋骨放射性核素，如钚、Am和 Ra对健康构成重大风险， 关心目前的模型用于建立“安全”限度， 保护人类免受体内沉积的阿尔法的有害影响， 放射性核素是基于不完整的数据，在某些情况下， 错误的假设。当前模式的一些缺陷 包括不正确的假设之间的分配核素 松质骨和皮质骨，Pu在骨上的掺入和保留 表面，骨内膜细胞组成的性质，以及 骨髓沉积的贡献。使用独特而广泛的 申请人拥有的标本集 从以前的比格犬研究中，本模型的缺陷 将按照以下目标处理这些问题。1)静态和动态 来自骨部位的物理数据和相关的剂量测定参数将 被确定。2)从中子诱导放射自显影（NIAR）， 将确定对于局部剂量模型重要的组织参数， 包括骨组织和骨髓3)使用荧光染料- 基于组织形态计量学方法， 不同骨部位的特征将与Pu 在同一地点的浓度。4)骨细胞面积密度 对特定细胞的辐射剂量和命中频率进行量化 人口将被确定。局部剂量模型将被关联 已知特定部位肿瘤发生的概率， 外推到人类身上将获得暴露于钚的人骨， 获得静态和局部剂量测定数据。这将提供一个更强大的 将动物数据与人类数据进行比较的基础。本研究将提供 一个更准确的生物动力学剂量/效应模型，基于 实验数据辅以人类观察，用于预测 人体暴露于趋骨放射性核素的后果。这些 研究还将提供有关 金属在骨骼组织中的生物学行为。

DESCRIPTION Exposure to bone-seeking radionuclides such as Pu, Am and Ra presents a substantial health risk and is of considerable public concern. The present models used to establish "safe" limits and to protect humans from the harmful effects of internally-deposited alpha emitting nuclides are based on incomplete data and in some cases clearly erroneous assumptions. Some of the deficiencies in the current model include incorrect assumptions for the partitioning of nuclides between trabecular and cortical bone, incorporation and retention of Pu on bone surfaces, the nature of the cellular composition of the endosteum, and contribution of marrow deposits. Using a unique and extensive collection of specimens, that the aplicants have in their possession from previous beagle dog studies, the deficiencies in the present model will be addressed with the following aims. 1) Static and dynamic physical data from bone sites and associated dosimetric parameters will be determined. 2) From neutron-induced autoradiographs (NIAR), the tissue parameters important for a local dose model will be determined, including osseous tissue and marrow contents. 3) Using fluorochrome- based histomorphometric methods, the remodelling and turnover characteristics of different bone sites will be correlated with Pu concentrations at these same sites. 4) Areal bone cell densities will be quantified and radiation doses and hit frequencies to specific cell populations will be determined. The local dose model will be correlated with known probabilities of tumor occurrence at specific sites and then extrapolated to humans. Pu-exposed human bone will be obtained and static and local dosimetric data obtained. This will provide a stronger basis for comparing the animal data with human. This study will provide a considerably more accurate biokinetic dose/effect model, based on experimental data supplemented with human observations, for predicting the consequences of human exposure to bone-seeking radionuclides. These studies will also provide fundamental new knowledge about the biokinetics of metals in skeletal tissues.