OZONE DOSIMETRY USING RADIOACTIVE AND STABLE ISOTOPES

使用放射性同位素和稳定同位素进行臭氧剂量测定

• 批准号: 2155380
• 负责人: MICHAEL L RUSSELL
• 金额: $ 17.03万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2155380
• 关键词: autoradiography; diagnostic respiratory lavage; gamma radiation; guinea pigs; hamsters; laboratory mouse; lipids; lung; lung alveolus; nasopharynx; ozone; particle accelerators; particle counter; pulmonary respiration; radiation dosage; radiotracer; species difference; stable isotope; trachea

Ozone induces toxic damage to the lung at a small but specific site, the alveolar region most proximal to the terminal bronchiole. Distal alveoli are spared, thus suggesting the presence of either a decreasing O3 dose gradient within the alveolar region or a difference in cellular susceptibility. Because of resolution limitations no experimental studies have ever demonstrated the alveolar region dose gradient. The final dose that reaches this proximal alveolar region is regulated by 03 uptake within the nasopharynx and tracheobronchial tree. Using radioactive and stable oxygen isotopes as 03 dosimetry tracers we will test the hypothesis that a significant alveolar region dose gradient exists causing the proximal region to absorb substantially more 03 than the distal region, and that the nasopharynx acts as a major determinate of alveolar 03 uptake. Oxygen-l5 labeled 03 (15-OOO) will be generated using a cyclotron, and laboratory animals will be given an acute exposure. The radioactivity of major tissues such as the nasopharynx, trachea, individual lung lobes, and extra-pulmonary tissues will be measured using a gamma-ray counter. Intraspecies comparisons in rats and interspecies comparisons between mice, hamsters, rats, and guinea pigs will be examined for 03 deposition differences. Mechanical ventilation will be used to investigate the effect of ventilatory parameter alteration on dosimetry. The elution profile of 15-OOO reaction products from the trachea will be assessed for those products which stay within the airway because they are unable to diffuse in aqueous media. The lipid vs. non-lipid components of 15-OOO reaction products in bronchoalveolar lavage fluid will be measured. The major functional compartments containing 03 reaction products such as lipid vs. non-lipid and aqueous soluble vs. non-soluble whole lung will be analyzed using 18-O3. The 18-O3 will be analyzed using Charged Particle Activation Analysis (CPAA) where the oxygen-18 is converted to fluorine-18, a radioisotope which decays by positron release. CPAA followed by positron - track autoradiography will be used to demonstrate and quantify 18-O3 gradients within the alveolar region of lung sections. This proposed investigation will provide an experimentally-based analysis of 03 dosimetry throughout the respiratory tract.

臭氧在一个小但特定的部位诱导肺有毒损害， 肺泡区域最靠近末端支气管。远端肺泡 幸免，因此表明存在任何降低的O3剂量 肺泡区域内的梯度或细胞差异 敏感性。由于解决限制没有实验研究 曾经证明牙槽区剂量梯度。最后剂量 到达该近端牙槽区域的调节由03吸收调节 在鼻咽和气管上树内。使用放射性和 稳定的氧同位素作为03剂量法示踪剂，我们将检验假设 存在明显的牙槽区剂量梯度，导致 近端区域吸收比远端区域高得多的03个区域 并且鼻咽是肺泡03的主要决定 吸收。将使用Cyclotron生成标记为03（15-OOO）的氧气L5 和实验动物将受到急性暴露。 放射性 在鼻咽，气管，单个肺裂片等主要组织中 并将使用伽马射线计数器测量肺外组织。 种内比较大鼠和种间比较 将检查老鼠，仓鼠，大鼠和豚鼠的沉积 差异。机械通气将用于研究效果 剂量法上的通气参数改变。洗脱资料 将评估来自气管的15个OOO反应产品 由于无法扩散而留在气道内的产品 在水性媒体中。 15-OOO反应的脂质与非脂质成分 将测量支气管肺泡灌洗液中的产品。专业 含有03种反应产物（例如脂质VS）的功能室室。 将分析非脂溶性和水溶性可溶性与非溶解的全肺 使用18-O3。将使用带电的粒子激活分析18-O3 分析（CPAA），其中氧-18转化为氟-18，a 推广释放衰减的放射性同位素。 CPAA随后是正面 - 轨道自显影术将用于演示和量化18-O3 肺切片肺泡区域内的梯度。 这提出了 调查将提供基于实验的03分析 整个呼吸道的剂量法。