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.
D000336:Aerosols; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001345:Autoradiography; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride; D002250:Carbon Radioisotopes; D002452:Cell Count; D004247:DNA / Q000096:biosynthesis; D004347:Drug Interactions; D006909:Hydroxyproline / Q000032:analysis; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000336:Aerosols; D002250:Carbon Radioisotopes; D002104:Cadmium; D014316:Tritium; D004247:DNA; D019256:Cadmium Chloride; D006909:Hydroxyproline; D010100:Oxygen; D013936:Thymidine