Correlation of biochemical and morphological changes induced by chemical injury to the lung

Stewart, BW; Le Mesurier, SM; Lykke, AWJ

HERO ID

62397

Reference Type

Journal Article

Year

1979

Language

English

PMID

509695

HERO ID 62397
In Press No
Year 1979
Title Correlation of biochemical and morphological changes induced by chemical injury to the lung
Authors Stewart, BW; Le Mesurier, SM; Lykke, AWJ
Journal Chemico-Biological Interactions
Volume 26
Issue 3
Page Numbers 321-338
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.
Pmid 509695
Wosid WOS:A1979HL46500009
Is Certified Translation No
Dupe Override No
Comments Chem. Biol. Interact. 26: 321-338.
Is Public Yes
Language Text English
Keyword Animals; Carbon Tetrachloride/*toxicity; Carcinogens/*toxicity; DNA/biosynthesis; Female; Gasoline/*toxicity; Injections, Intravenous; Methylcholanthrene/toxicity; Microscopy, Electron; Nitrosomethylurethane/toxicity; Petroleum/*toxicity; Pulmonary Alveoli/*drug effects/metabolism/ultrastructure; RNA/biosynthesis; Rats; Trichloroethylene/*toxicity; 0 (Carcinogens); 0 (Gasoline); 0 (Petroleum); 56-23-5 (Carbon Tetrachloride); 56-49-5 (Methylcholanthrene); 615-53-2 (Nitrosomethylurethane); 63231-63-0 (rna); 79-01-6 (Trichloroethylene); 9007-49-2 (dna)
Is Qa No