Cadmium-induced lung injury: cell kinetics and long-term effects.

The effects of exposure to CdCl2 aerosols followed by hyperoxia were studied in mouse lung. Special emphasis was placed on analysis of cell proliferation following injury. Male Balb/c mice were exposed to aerosols of 4.9 micrograms Cd/liter for 1 hr while controls were exposed to water aerosols. Immediately after, half of each group was placed in 80% O2 for 6 days, while the rest were left in room air. Three endpoints were used to assess lung injury; measurement of hydroxyproline, [14C]thymidine incorporation into DNA, and histopathology. Parenchymal and bronchiolar labeling indices were determined following autoradiography. A 1-hr exposure to CdCl2 aerosols caused marked cell proliferation in the lung with the peak of cell labeling occurring at Day 5. In animals exposed to both CdCl2 + 80% O2, the cell labeling peak was delayed until Day 9. Cell differentiation studies showed a delay in the peak of type II epithelial cell and endothelial cell division when CdCl2 exposure was followed by the 80% O2 treatment. On Day 15 most of the labeled cells were identified as interstitial cells in both treated groups. Bronchiolar cell labeling was suppressed at the early time period in the Cd + O2 group. With time, the histologically visible lung lesions tended to resolve in animals exposed to CdCl2 or CdCl2 and 80% O2, whereas total pulmonary hydroxyproline remained at all times (3, 6, and 12 months) significantly higher in Cd-treated animals when compared to controls. It was concluded that acute lung injury by a toxic inhalant can be amplified if there is an initial delay in pulmonary cell proliferation following an acute insult.