Damage and Repair of Mouse Bronchial Epithelium following Acute Inhalation of Trichloroethylene

Abstract

The time-course of damage and repair in the bronchial epithelium of the mouse was studied morphometrically after a single inhalation of trichloroethylene (TCE). Mice were exposed for 30 min to 500, 1000, 2000, 3500, or 7000 ppm of TCE under controlled conditions and sacrificed after 2 and 24 h, and 2, 5, and 7 days. At all TCE concentrations, the damage consisted of dilation of endoplasmic reticulum and was selective for nonciliated cells throughout the bronchial tree. Damage was quantitatively evaluated by counting the percentage of vacuolated cells. Injury was maximal 24 h after exposure and was significantly (p < 0.05) higher in bronchi with a diameter smaller than 0.4 mm (67.0% ± 8.5%) in comparison with larger bronchi (34.0% ± 13.2%). Cell turnover was studied by autoradiography after [³H]thymidine injection. Following TCE inhalation, the percentage of [³H]thymidine labeled cells, which in the controls was virtually zero, increased to a maximum of 13.5% ± 6.8% (average at all doses) 48 h after treatment and then rapidly decreased to baseline values at 7 days (0.2% ± 0.1%). Repair of some cells occurred after 24 h, and at 48 h the percentage of vacuolated cells decreased and became significantly related (p < 0.01) to the administered TCE dose (2.4% ± 1.4% and 21.2% ± 6.0% average in the 500 and 7000 ppm groups, respectively). Repair of bronchial epithelium took place by both recovery of less damaged cells and proliferation of residual nonciliated cells, leading to restoration of the normal ratio between ciliated and nonciliated cells.