Nikula K J, Wilson D W
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Fundam Appl Toxicol. 1990 Jul;15(1):121-31. doi: 10.1016/0272-0590(90)90169-k.
Although ozone-induced epithelial injury in vivo has been morphologically characterized, effects of gaseous oxidants on respiratory epithelium in organ culture, where tissue organization is maintained but systemic influences are eliminated, have not been thoroughly investigated. In this study, we exposed tracheal organ cultures from rats to 95% oxygen and 1 ppm ozone, alone and in combination, to determine (1) whether epithelial responses to ozone similar to those observed in vivo occur in airways separated from systemic physiologic, secretory, and inflammatory reactions; (2) whether concentrations of oxygen sufficient to potentially cause oxidant injury result in morphologic epithelial alterations similar to those that occur in ozone toxicity; and (3) if the combined oxidant insult of oxygen and ozone results in more severe damage to the tracheal epithelium than occurs with ozone in air. Tracheal organ cultures were exposed to filtered air and 5% carbon dioxide; filtered air, 5% carbon dioxide, and 1 ppm ozone; 95% oxygen and 5% carbon dioxide; or 95% oxygen, 5% carbon dioxide, and 1 ppm ozone for 96 hr. Light- and quantitative electron-microscopic evaluation showed that epithelia exposed to 1 ppm ozone in air exhibited loss of ciliated cells and ciliated cell damage. The epithelia exposed to 95% oxygen and 5% carbon dioxide were pseudostratified, columnar, ciliated, and hyperplastic. Epithelia exposed to 95% oxygen plus 1 ppm ozone were stratified and nonciliated or very sparsely ciliated. The predominant cell types in epithelia exposed to oxygen plus ozone were serous cells and metaplastic cells, and focal aggregates of adherent necrotic cells were present. We conclude that there was a synergism between oxygen and ozone exposure leading to enhanced epithelial injury and metaplasia.
尽管体内臭氧诱导的上皮损伤已有形态学特征描述，但气态氧化剂对器官培养中呼吸上皮的影响尚未得到充分研究，在器官培养中，组织结构得以维持，但排除了全身影响。在本研究中，我们将大鼠气管器官培养物单独或联合暴露于95%氧气和1 ppm臭氧中，以确定：（1）在与全身生理、分泌和炎症反应分离的气道中，上皮对臭氧的反应是否与体内观察到的相似；（2）足以潜在导致氧化损伤的氧气浓度是否会导致与臭氧毒性中出现的形态学上皮改变相似的改变；（3）氧气和臭氧的联合氧化损伤是否会对气管上皮造成比空气中臭氧更严重的损害。将气管器官培养物暴露于过滤空气和5%二氧化碳；过滤空气、5%二氧化碳和1 ppm臭氧；95%氧气和5%二氧化碳；或95%氧气、5%二氧化碳和1 ppm臭氧中96小时。光镜和定量电镜评估显示，暴露于空气中1 ppm臭氧的上皮出现纤毛细胞丢失和纤毛细胞损伤。暴露于95%氧气和5%二氧化碳的上皮为假复层柱状纤毛上皮且增生。暴露于95%氧气加1 ppm臭氧的上皮为分层且无纤毛或纤毛非常稀疏。暴露于氧气加臭氧的上皮中的主要细胞类型为浆液细胞和化生细胞，且存在附着坏死细胞的局灶性聚集。我们得出结论，氧气和臭氧暴露之间存在协同作用，导致上皮损伤和化生增强。
