POPULATION RISK MODEL FOR ALPHA INDUCED BONE NEOPLASMS

人们普遍认识到，暴露于钚、Am、Re等寻骨性放射性核素的后果是众所周知的，并引起公众的极大关注。目前的保护模型在很大程度上是基于统计假设，只有很少的生物学或实验数据。虽然这些模型可能适用于设定暴露极限，但我们的目标是继续推导出一个基于实验的辐射剂量-组织相互作用的生物动力学剂量学模型，该模型将预测肿瘤的发生、潜伏期、位置和频率。利用现有的数据和组织档案，将实现以下目标：L)基于中子诱导放射自显影的图像分析方法，将确定比格犬在239Pu单体照射后的组织分区、细胞分布和辐射剂量随时间的变化。2)形态计量学和形态学方法将在用于239Pu定位和剂量学评估的同一标本中定义比格尔骨组织的生物学。3)建立在骨骼组织中分布、掺入和滞留的相关生物学决定因素。这些指标包括Pu在皮质/小梁骨中的亲和力比率；松质骨在脂肪/红骨髓部位的亲和力；成骨细胞活跃/静止表面上的表面沉积。4)根据从AIMS 1-3获得的信息，并结合先前寿命研究中的肿瘤信息，将继续开发比格犬的预测肿瘤模型。一些重点将放在“组织权重系数”的确定(例如，骨骼内膜与肝脏)和潜在的反向剂量率效应的评估上。5)人类生物学成分将从文献和档案中的一些人类材料中确定。其组织特征可能在预测肿瘤模型中很重要，包括红色/脂肪骨髓随年龄的分布，骨骼的转换和代谢，以及假定的靶细胞密度。6)人体剂量学信息将主要从Beagle模型预测，但通过对人体骨骼中239Pu的分析得到证实。将对暴露于此的人类骨骼进行NIAR分析。人体样本由USTUR提供，一些组织可能来自俄罗斯严重暴露的人类(玛雅克工作人员)。7)从小猎犬的实验模型和为人类开发的数据中，将为人类构建一个基于生物学的“肿瘤预测”模型。这些研究将为Pu和其他寻骨者的生物学行为提供新的知识，并提高预测暴露风险的能力。

The consequences of exposures to bone-seeking radionuclides including plutonium, americium, radium and others are well recognized and of considerable public concern. Current protection models are based largely on statistical assumptions with only minimal biological or experimental data. While these models may be suitable for the setting of exposure limits, our goal is to continue to derive an experimentally based biokinetic-dosimetric model of radiation dose-tissue interactions that will be predictive of tumor occurrence, latency periods, location, and frequency. Using existing data and tissue archives, the following aims will be accomplished: l) Neutron Induced Autoradiography (NIAR) based image analysis methods will determine tissue compartments, cellular distributions and radiation doses with time after monomeric 239Pu exposures in beagle dogs. 2) Morphometric, and morphological methods will define the biology of the beagle osseous tissues in the same specimens used for 239Pu localization and dosimetric evaluations. 3) To establish the relative biological determinants of actinide distribution, incorporation and retention in skeletal tissues. These include the affinity ratios for Pu in cortical/trabecular bone; cancellous bone in fatty/red marrow sites; surface deposition on osteoblastic active/resting surfaces. 4) From information obtained from Aims 1-3 and combined with tumor information from previous lifespan studies, a predictive tumor model for the beagle dog will continue to be developed. Some emphasis will be placed on the determination of "tissue weighting factors" (e.g. skeletal endosteum vs. liver) and evaluation of a potential inverse dose rate effect. 5) The human biology component will be determined from the literature and from some human material in archive. The tissue characteristics of that are likely to be important in the predictive tumor model include distribution of red/fatty marrow with age, skeletal turnover and metabolism, and densities of putative target cells. 6) Human dosimetry information will mostly be predicted from the beagle model, but confirmationed by analysis of 239Pu in the human skeleton. NIAR analyses of bones from exposed humans will be done. The human samples are provided by the USTUR and some tissues may be obtained from heavily exposed humans in Russia (Mayak workers). 7) From the experimentally derived model for the beagle and from data developed for the human, a biologically-based "tumor predictive" model will be constructed for the human. These studies will provide new knowledge on the biological behavior of Pu and other bone-seekers and an improved capability to predict the risks of exposure.