RESIDUAL RADIATION DAMAGE IN NORMAL TISSUES

这项研究的目的是更详细地了解 参与正常组织对 辐射 这些研究的基本原理是基于目前的 在正常组织放射生物学中关于 “晚期”响应正常组织中损伤的发病机制，即， 薄壁组织与基质，以及“晚期” 对正常组织和慢性组织损伤的反应。 的 受照射组织在数月内恢复的能力 至初次接触后数年（根据 剩余损伤）的确定， 延迟响应的正常组织将在更晚和更长时间内恢复 比急性反应正常组织的时间，反映 消耗对反应特异的关键细胞，而 慢性组织损伤的恢复模式可能与所有 反映共同细胞病因的组织。 一旦恢复 轮廓已经定义，其他研究将调查 任何观察到的再治疗变化的潜在机制 宽容 拟议的工作分为三个具体目标。 第一个建议是确定后期的恢复模式， 反应正常组织和慢性反应。 更 具体而言，这些研究将侧重于两个迟来的反应， 正常组织、肾和肺，以及肠中的慢性损伤， 皮肤和肺。 目标2将研究其机制 任何观察到的重新开始治疗反应变化的基础， 以前被辐射过的组织。 这些研究将涉及 确定先前辐照的氧增强比 组织以及确定是否，何时以及在什么细胞中 发生扩散。 目标3将研究 恢复完成时或恢复期间， 刺激增殖。 这些研究应该增加我们的 了解海洋生物的耗竭和再增殖动力学， 用于晚期应答正常组织和慢性炎症的靶细胞 所有受照射组织以及 深入了解组织中涉及的基本过程 损伤和修复。 这些研究的潜在重要性， 临床放射治疗是他们应该提供放射治疗师 定量数据和指导方针来设计治疗方案 当对先前照射部位进行再治疗时， 必要

The goal of this research is to understand in greater detail the mechanisms involved in the responses of normal tissues to radiation. The rationale for these studies is based on the current controversy in normal tissue radiobiology concerning the pathogenesis of damage in "late" responding normal tissues, i.e., parenchyma vs. stroma, and the distinction between "late" responding normal tissues and chronic tissue damage. The capacity of irradiated tissues to recover over a period of months to years after initial exposure (as assessed by the amount of residual damage) will be determined with the expectation that late responding normal tissues will recover later and over a longer period of time than acute responding normal tissues, reflecting depletion of a critical cell specific for the response whereas the recovery pattern for chronic tissue damage may be similar for all tissues reflecting a common cellular etiology. Once the recovery profiles have been defined, other studies will investigate the mechanisms underlying any observed changes in retreatment tolerance. The proposed work is divided into three specific aims. The first proposes to determine the recovery pattern for late responding normal tissues and for chronic responses. More specifically, these studies will focus on two late responding normal tissues, kidney and lung, and chronic damage in bowel, skin, and lung. Aim 2 will then investigate the mechanisms underlying any observed changes in retreatment response in previously irradiated tissues. These studies will involve determining oxygen-enhancement ratios for previously irradiated tissues as well as to determine if, when, and in what cell proliferation occurs. Aim 3 will investigate the repair capacity of previously irradiated tissues when recovery is complete or during stimulated proliferation. These studies should increase our understanding of the kinetics of depletion and repopulation of the target cells for late responding normal tissues and for the chronic wave of damage common to all irradiated tissues as well as to provide insight into fundamental processes involved in tissue injury and repair. The potential importance of these studies to clinical radiotherapy is that they should provide radiotherapists with quantitative data and guidelines for designing treatment protocols when retreatment of a previously irradiated site is necessary.