BLOOD VESSELS AND NEUTRONS: QUANTITATIVE STUDIES

血管和中子：定量研究

• 批准号: 3347838
• 负责人: MELVIN L GRIEM
• 金额: $ 17.64万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-12-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3347838
• 关键词: X ray; blood vessels; capillary; cell population study; dosage; linear energy transfer; neutron radiation; radiobiology; tissue /cell culture; vascular endothelium

One of the problems facing clinical High-LET radiation is the late tissue changes associated with injury to the vascular system - in particular the capillaries - late effects associated with severe fibrosis. In vivo measurements of microvascular changes in the Sandison Clark ear chamber in the New Zealand rabbit and in vitro experiments using organ cultures of rabbit vascular cells are directed to provide pre-clinical information concerning the response of this tissue in vivo and in vitro. The effects on the microvasculature in vivo of graded single neutron doses (12.5-500 rads), fractionated neutron exposures, graded doses of x-rays and the interaction and possible potentiation of these two modalities will be evaluated. Early and intermediate vascular changes following single or combined treatment regimens will be scored and correlated by measuring the following parameters in vivo on capillaries, arterioles and venules: microvascular length, surface area and wall thickness. These parameters will be determined separately for capillaries, (less than or equal to 10Mu in diameter) larger vessels (greater than 10Mu dia.), and for the total microvasculature. From these measured parameters, microvascular volume, microvascular density/mm2 and a dilatation factor over time will be calculated. In vitro studies carried out in parallel will use comparable cultures of vascular endothelial and smooth muscle cells irradiated in vivo to further elucidate the role of these two most reactive cell populations in early and intermediate effects following radiation. Thus we will determine a) the neutron dose response (Do, Dq, LD-50) for microvasculature in vivo and its cellular components in vitro, b) the extent of early and intermediate injury and repair and c) the extent of differential sparing of capillaries by the use of fractionated regimens. Doses of neutron radiation and dose fractionation with this modality will be compared with already established observations made in these two systems with kilovoltage x-rays. The dynamics of RBE over dose and time in relation to these two clinically used modalities will be established. These quantitative experiments will provide valuable information to develop clinical strategies to minimize the late vascular changes in the use of High-L radiation in human cancer management.

临床高LET照射面临的问题之一是组织迟发 与血管系统损伤相关的变化-特别是 毛细血管--与严重纤维化相关的后遗症。活体内 老年人Sandison Clark耳室微血管变化的测量 新西兰白兔及其器官培养的体外实验 兔血管细胞被指示提供临床前信息 关于该组织在体内和体外的反应。 分级单次中子剂量对体内微血管的影响 (12.5-500拉德)、分次中子照射、分级X射线剂量和 这两种模式的相互作用和可能的增强作用将是 已评估。单个或多个血管病变的早期和中期血管改变 综合治疗方案将通过测量 毛细血管、小动脉和小静脉的活体参数如下： 微血管长度、表面积和壁厚。这些参数 将单独确定毛细血管，(小于或等于10Mu 直径)较大的容器(大于10Mu直径)，以及 微血管系统。根据这些测量的参数，微血管体积， 随着时间的推移，微血管密度/mm2和扩张系数将是 计算出来的。平行进行的体外研究将使用类似的 照射后血管内皮细胞和血管平滑肌细胞的体内培养 为了进一步阐明这两个最活跃的细胞群体的作用 在辐射后的早期和中期影响。 因此，我们将确定a)的中子剂量响应(DO，DQ，LD-50 体内微血管构筑及其体外细胞成分，b) 早期和中期损伤和修复的程度以及c)程度 通过使用分步疗法对毛细血管进行差别化保留。 使用这种方式的中子辐射剂量和剂量分馏将 与在这两个系统中已经确定的观测结果进行比较 用千伏的X光。小鼠的RBE随剂量和时间的动态变化 将建立与这两种临床使用的模式的关系。 这些定量实验将提供有价值的信息以供开发 减少晚期血管病变使用的临床策略 L高放在人类癌症治疗中的作用。