Pinkerton K E, Ménache M G, Plopper C G
Institute of Toxicology and Environmental Health, University of California at Davis 95616, USA.
Res Rep Health Eff Inst. 1995 Mar(65 Pt 8-9):41-98; discussion 99-110.
The effect of ozone on the respiratory system is not confined to a single region or a specific cell type. Ozone-induced injury can occur at all levels of the respiratory system. However, the effects of this oxidant gas throughout the tracheobronchial tree and the lung parenchyma can be highly variable. The doses of ozone delivered to the various regions may also be different, and these differences may have a significant effect on the extent of injury. To examine the effects of chronic exposure to ozone on the lungs, we used a systematic sampling approach to perform morphometric, histochemical, and enzymatic analyses of selected airway generations and pulmonary acini arising from short and long airway paths of the tracheobronchial tree. The objectives of this study were to define compositional, cytochemical, and architectural changes that occur in epithelial cells of the airways and major tissue components of the pulmonary acini after 20 months of exposure to 0.0, 0.12, 0.5, or 1.0 parts per million (ppm)* ozone in male and female F344/N rats. We found in the trachea and bronchi significant alterations in stored secretory product following exposure to ozone, but no changes in epithelial thickness or the volume density of nonciliated cells. The volume density of nonciliated cells was significantly increased in terminal bronchioles arising from a long airway path (caudal region) of the left lung. The predominant change within the pulmonary acini was the extension of bronchiolar epithelium beyond the bronchiole-alveolar duct junction into alveoli. This change was concentration-dependent and site-specific, with ventilatory units arising from a short path (cranial region) of the left lung in male rats being most affected. The antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase were significantly elevated in the distal bronchiole to central acinus following 20 months of exposure to 0.5 or 1.0 ppm ozone. Changes in antioxidant enzyme levels were more variable in other airway generations. We conclude that the effects of long-term (20-month) exposure to ozone are dose-dependent and site-specific along the tracheobronchial tree and pulmonary acini of the lungs. With the tissue sampling strategies used in this study, for the first time microdosimetric relations between ozone concentrations and biological changes in precisely delineated regions of the lungs can be defined along the entire lower respiratory tract.
臭氧对呼吸系统的影响并不局限于单一区域或特定细胞类型。臭氧诱导的损伤可发生在呼吸系统的各个层面。然而，这种氧化性气体对整个气管支气管树和肺实质的影响可能差异很大。输送到各个区域的臭氧剂量也可能不同，这些差异可能对损伤程度产生重大影响。为了研究长期暴露于臭氧对肺部的影响，我们采用系统抽样方法，对气管支气管树短路径和长路径产生的选定气道节段和肺腺泡进行形态计量学、组织化学和酶学分析。本研究的目的是确定在雄性和雌性F344/N大鼠中，暴露于0.0、0.12、0.5或1.0百万分之一（ppm）*臭氧20个月后，气道上皮细胞和肺腺泡主要组织成分中发生的成分、细胞化学和结构变化。我们发现，暴露于臭氧后，气管和支气管中储存的分泌产物有显著改变，但上皮厚度或非纤毛细胞的体积密度没有变化。左肺长气道路径（尾侧区域）产生的终末细支气管中，非纤毛细胞的体积密度显著增加。肺腺泡内的主要变化是细支气管上皮延伸至细支气管-肺泡管连接处之外进入肺泡。这种变化具有浓度依赖性和部位特异性，雄性大鼠左肺短路径（头侧区域）产生的通气单位受影响最大。暴露于0.5或1.0 ppm臭氧20个月后，远端细支气管至中央腺泡中的抗氧化酶超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽S-转移酶显著升高。其他气道节段中抗氧化酶水平的变化更具变异性。我们得出结论，长期（20个月）暴露于臭氧的影响在气管支气管树和肺腺泡中具有剂量依赖性和部位特异性。通过本研究中使用的组织采样策略，首次能够沿整个下呼吸道确定臭氧浓度与肺精确划定区域内生物变化之间的微剂量关系。
