Carbon tetrachloride-induced changes in mixed function oxidases and microsomal cytochromes in the rat lung

The effects of a single exposure, by gastric intubation or inhalation, to carbon tetrachloride (CCL4) on rat lungs were assessed. By 1 to 7 days, focal areas of alveolar collapse, septal edema, and modification of type II pneumonocytes were observed. By 24 hours after exposure to the toxin, there were no identifiable changes in surfactant levels or distribution. Microsomes obtained from the lungs and prepared for analysis revealed marked decreases in cytochrome P-450 content and P-450-related N-demethylation of dimethylaniline. Only a transient reduction of cytochrome b5 occurred, with a rebound exceeding control values during the period of pulmonary healing. Whether the lung acted as an excretory route (following intubation) or as an absorption path (after inhalation) made little difference. Carbon tetrachloride had no effect on in vitro microsome composition and function unless supplemented with a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) generating system. Under these circumstances, there was a reduction in both cytochromes b5 and P-450. Our data indicate that a considerable chemical modification of the pulmonary tissues had taken place, with no accompanying easily recognized changes in cellular structure. Furthermore, evidence for the in vitro destruction of pulmonary microsomal cytochromes P-450 and b5, unrelated to peroxidation, is indicated by these findings.