POPULATION RISK MODEL FOR ALPHA INDUCED BONE NEOPLASMS

ALPHA 诱发骨肿瘤的人群风险模型

• 批准号: 2848366
• 负责人: Ray Lloyd
• 金额: $ 18.93万
• 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 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2848366
• 关键词: actinides; americium; autoradiography; biological models; bone density; bone metabolism; bone neoplasms; cancer risk; cell population study; cell type; clinical research; dogs; hematopoietic stem cells; human population study; human tissue; osteocytes; plutonium; radiation dosage; radiobiology; radionuclides; radiotracer

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.

暴露于趋骨放射性核素，包括钚、镅、镭和其他放射性核素的后果已得到广泛承认，并引起公众的极大关注。目前的保护模式主要基于统计假设，只有很少的生物或实验数据。虽然这些模型可能适用于设定暴露限值，但我们的目标是继续推导出基于实验的辐射剂量-组织相互作用的生物动力学剂量测定模型，该模型将预测肿瘤发生、潜伏期、位置和频率。使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（NIAR）的图像分析方法将确定比格犬中单体239 Pu暴露后随时间的组织隔室、细胞分布和辐射剂量。2)形态测定和形态学方法将确定用于239 Pu定位和剂量测定评价的相同样本中比格犬骨组织的生物学。3)建立锕系元素在骨骼组织中分布、掺入和滞留的相关生物学决定因素。这些包括Pu在皮质骨/小梁骨中的亲和力比;脂肪/红骨髓部位的松质骨;成骨细胞活性/静止表面上的表面沉积。4)根据从目的1-3获得的信息，并结合既往寿命研究的肿瘤信息，将继续开发比格犬的预测肿瘤模型。重点将放在确定“组织加权因子”（例如骨骼骨内膜与肝脏）和评价潜在的反向剂量率效应上。5)人类生物学成分将根据文献和档案中的一些人类材料来确定。其组织特征可能在预测肿瘤模型中很重要，包括红/脂肪骨髓随年龄的分布、骨骼转换和代谢以及推定靶细胞的密度。6)人体剂量学信息将主要从比格犬模型预测，但通过分析人体骨骼中的239 Pu进行确认。将对受辐射人体骨骼进行NIAR分析。人体样本由俄罗斯科学技术研究所提供，某些组织可能来自俄罗斯严重接触的人（Mayak工人）。7)根据实验获得的比格犬模型和为人类开发的数据，将为人类构建基于生物学的“肿瘤预测”模型。这些研究将为钚和其他趋骨物质的生物学行为提供新的知识，并提高预测接触风险的能力。