title: Correlation of biochemical and morphological changes induced by chemical injury to the lung.
abstract: Comparison has been made of injury to the rat pulmonary alveolar parenchyma evoked by intravenous injection of N-nitrosomethylurethane, intratracheal instillation of 3-methylcholanthrene or repeated inhalation for up to 15 days of carbon tetrachloride, trichloroethylene or gasoline vapour. Biochemical analyses, including assessment of rates of RNA and DNA synthesis and secretion of pulmonary surfactant, were correlated with morphological changes determined by electron microscopy. Single doses of N-nitrosomethylurethane or 3-methylcholanthrene inhibited incorporation of [14C] orotate into lung RNA 1--3 days after treatment. Daily exposure for 30 min to carbon tetrachloride or trichloroethylene vapour caused less marked reduction in orotate incorporation. Ultrastructural examination revealed that 3-methylcholanthrene toxicity was characterised by cytoplasmic change including disruption of surfactant lamellaie of Type 2 pneumocytes and variable degenerative changes Type 1 pneumocytes. Eight to ten days after treatment, the morphological evidence of hypertrophy/hyperplasia and transformation of Type 2 pneumocytes correlated well with biochemical evidence of stimulated incorporation of [3H]thymidine. Inhalation of carbon tetrachloride or trichloroethylene vapour produced milder responses including occasional degenerative changes in Type 1 pneumocytes, reduced numbers of surfactant lamellae in Type 2 pneumocytes and no change in [3H]thymidine incorporation. In contrast to the gradation of injury produced by the various chemicals, all procedures caused a marked and reproducible reduction in secretion of pulmonary surfactant as determined by endobronchial lavage. Following solvent inhalation, reduced recovery of surfactant was detected within 5 days of repeated exposure and thereafter no further change in this depressed level resulted from continued exposure for a further 10 days. The data are discussed in terms of a generalised pattern of response by pulmonary alveolar tissue to chemical injury and the apparent sensitivity of surfactant secretion as an indicator of damage to the lung.
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005742:Gasoline / Q000633:toxicity*; D007275:Injections, Intravenous; D008748:Methylcholanthrene / Q000633:toxicity; D008854:Microscopy, Electron; D009605:Nitrosomethylurethane / Q000633:toxicity; D010578:Petroleum / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D014241:Trichloroethylene / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D005742:Gasoline; D010578:Petroleum; D014241:Trichloroethylene; D008748:Methylcholanthrene; D009605:Nitrosomethylurethane; D012313:RNA; D004247:DNA; D002251:Carbon Tetrachloride