RADIATION STUDIES IN VASCULAR TISSUE

临床放射治疗面临的问题之一是晚期组织 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晚期效应。 体内 兔耳微血管的测量 使用血管细胞的原代培养物的实验涉及 提供关于缓解的完全定量的临床前信息 在体内和体外的实验中。 研究了不同剂量X射线对在体微血管的影响， 低氧、WR 2721和V2兔对这些作用的改变 将对癌进行定量。 缺氧和辐射防护剂WR 2721将 单独和组合研究，以确定保护程度 辐射损伤可使微血管组织， 体内和体外。 我们建议建立一个兔耳腔肿瘤模型 用V2兔肿瘤模型评价放射线对肿瘤细胞的急性效应。 肿瘤微血管床与肿瘤生长及相关肿瘤 生长模式与血管损伤模式，以确定最佳的 最大化肿瘤杀伤的治疗策略。 单次或联合剂量调整后的急性和晚期血管变化 将通过测量以下指标对治疗方案进行评分和关联 毛细血管、小动脉和小静脉的体内参数：微血管 长度、表面积和壁厚。 这些参数将 分别测定毛细管（直径10）更大的船只和 整个微血管系统 从这些测量的参数，微血管 体积、微血管密度/mm 2和随时间的扩张因子将是 计算了 平行进行的体外研究将使用相当的培养物 血管内皮细胞和平滑肌细胞的辐射在体内和 进一步阐明这两种最具反应性细胞的作用 在治疗后的早期和中期效应人群中。 我们的体内和体外数据的计算机化分析将提供DO，Dg， Beta/Alpha、N、SLD和原位修复能力以及线性 微血管的二次和单次命中-多目标数据拟合程序 根据尺寸（10 m至150 m，10 m箱）和功能分类 （小动脉、小静脉、毛细血管）。

One of the problems facing clinical radiation therapy is the late tissue changes associated with injury to the vascular system - in particular the capillaries - and late effects associated with severe fibrosis. In vivo measurements of microvascular changes in rabbit ear chamber and in vitro experiments using primary cultures of vascular cells are directed to provide fully quantitative pre-clinical information concerning the response of this tissue in vivo and in vitro. The effects of graded doses of x-rays on the microvasculature in vivo and the modification of these effects by hypoxia, WR 2721 and the V2 rabbit carcinoma will be quantitated. Hypoxia and the radioprotector WR 2721 will be studied singly and in combination to determine the degree of protection from radiation injury which can be conferred to microvascular tissue in vivo and in vitro. We propose to develop a rabbit ear chamber tumor model using the V2 rabbit carcinoma to evaluate acute effects of radiation on the tumor microvascular bed in relation to tumor growth and correlate tumor growth patterns with vascular injury patterns to determine the optimal therapeutic strategy to maximize tumor kill. Acute and late vascular changes following single or combined dose modifying 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 (10 in dia.) larger vessels 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 done in parallel will use comparable cultures of vascular endothelial and smooth muscle cells irradiated in vivo and in vitro to further elucidate the role of these two most reactive cell populations in early and intermediate effects following treatment. Computerized analysis of our in vivo and in vitro data will provide DO, Dg, Beta/Alpha, N, SLD and in situ repair capability as well as linear quadratic and single hit-multitarget data fitting routines for microvessels separated according the size (10 m to 150 m in 10 m bins) and function (aterioles, venules, capillaries).