BROMOBENZENE-INDUCED CLARA CELL DAMAGE: THE CONTRIBUTION OF CYTOCHROME P-450 SYSTEM LOCALIZED IN THE CLARA CELL

Abstract

The relationship between the alterations of different pulmonary drug metabolizing systems and the selective damages of Clara cells in ddY mice caused by bromobenzene treatment was investigated in order to elucidate the mechanism of bromobenzene-induced pneumotoxicity. Pulmonary drug metabolizing systems showed different responses to oral administration of bromobenzene (5 mmole/kg body weight) in mice at 8 and 24 hours. The time-dependent decrease of coumarin hydroxylase activity was the severest compared to other drug metabolizing enzymes. Bromobenzene treatment caused selective damages of the Clara cells without influencing the ciliated bronchiolar cells and alveolar type II cells, and the degrees of Clara cell damage became severer with time. These results suggest that the degradation of pulmonary coumarin hydroxylase is closely related to the selective damage of Clara cells induced by bromobenzene, and this enzyme contributes to the occurrence of bromobenzene-induced Clara cell damages.