Lee K P, Valentine R, Bogdanffy M S
Central Research & Development, Du Pont Company, Haskell Laboratory for Toxicology & Industrial Medicine, Newark, Delaware 19714.
Toxicol Pathol. 1992;20(3 Pt 1):376-93. doi: 10.1177/019262339202000308.
This study was conducted to investigate the initial tissue damage, morphogenesis, and reversibility of nasal lesions induced by the inhalation of dibasic esters (DBE). Young male rats were exposed, nose-only, to an aerosol/vapor mixture of DBE at a concentration of 5,900 mg/m3 for 4 hr and subsequently killed at 1, 4, 7, 14, 21, and 42 days after exposure. Nasal lesions were distributed along major inspiratory airflow routes. Widespread epithelial denudation occurred in the anterior nasal cavity, but the lesions were confined to the dorsal meatus, adjacent the nasal septum, and the lateral middle meatus in the mid-anterior nasal cavity. The lesions were markedly less severe in the posterior nasal cavity and sharply confined to the tips of dorsal ethmoturbinates and adjacent nasal septum. The damaged cuboidal/nonciliated and respiratory epithelium in the anterior nasal cavity regained a normal structure by 4 and 7 days postexposure, respectively. The regeneration of damaged olfactory epithelium was related to the severity of initial tissue damage. Slightly damaged epithelium regained a normal appearance within 1-2 weeks, but the extensively denuded epithelium of the dorsal meatus in the anterior nasal cavity failed to regain a normal structure by 6 weeks. The sustentacular cells of the olfactory epithelium appeared to be the initial site of DBE nasal injury. In the early stages of regeneration, the epithelium was repaired by proliferating stem cells derived from basal cells. Numerous mitotic figures and bromodeoxyuridine labeling were found in the regenerating basal cells, stem cells, and sustentacular cells at 4 and 7 days. As repair processes advanced, the numbers of olfactory neurons and vesicles were increased with a proportional decrease in stem cells.
本研究旨在调查吸入二元酯（DBE）引起的鼻腔病变的初始组织损伤、形态发生和可逆性。将年轻雄性大鼠仅经鼻暴露于浓度为5900 mg/m3的DBE气溶胶/蒸汽混合物中4小时，随后在暴露后1、4、7、14、21和42天处死。鼻腔病变沿主要吸气气流路径分布。前鼻腔出现广泛的上皮剥脱，但病变局限于鼻腔背侧通道、鼻中隔相邻处以及鼻腔中前部的外侧中鼻道。后鼻腔的病变明显较轻，且严格局限于筛骨背侧鼻甲尖端和相邻的鼻中隔。前鼻腔受损的立方上皮/无纤毛上皮和呼吸上皮分别在暴露后4天和7天恢复正常结构。受损嗅觉上皮的再生与初始组织损伤的严重程度有关。轻度受损的上皮在1 - 2周内恢复正常外观，但前鼻腔背侧通道广泛剥脱的上皮在6周时未能恢复正常结构。嗅觉上皮的支持细胞似乎是DBE鼻腔损伤的初始部位。在再生早期，上皮由源自基底细胞的增殖干细胞修复。在第4天和第7天，在再生的基底细胞、干细胞和支持细胞中发现了大量有丝分裂象和溴脱氧尿苷标记。随着修复过程的推进，嗅觉神经元和小泡的数量增加，干细胞数量相应减少。
