THE SEQUENTIAL CHANGE OF A NAPHTHALENE-INDUCED BRONCHIOLAR DAMAGE AND OF PULMONARY CYTOCHROME P-450 IN MICE

Abstract

Male ICR mice were exposed to 2 mmol/Kg body weight of naphthalene by single intraperitoneal injection. Treated mice were killed consecutively from 2 hours to 14 days after treatment. Tissues were examined for alterations of the bronchiolar epithelial cells by light and electron microscopes, and for amount of pulmonary cytochrome P-450 by ascorbate PES method. Morphologically, naphthalene caused a remarkable increase in smooth-surfaced endoplasmic reticulum of the Clara cells within 4 hours after treatment and the subsequent lesions including the exfoliated ciliated cells. Foamy cell-like Clara cells were observed in the bronchiolar lumen from 6 to 24 hours followed by a pronounced increase in number of flat ciliated cells covering the denuded surface of the bronchiolar tree 48 hours after treatment. These lesions wer almost completely recovered 7 days after treatment. The amount of pulmonary cytochrome P-450 increased promptly and reached up to the maximum level 4 hours after treatment, paralleling with the remarkable increase in smooth surfaced endoplasmic reticulum of the Clara cells. Thereafter, cytochrome P-450 showed a decrease in amount simultaneously with degeneration and desquamation of the Clara cells and reduced by 40% of control amount 24 hours after treatment. There results seem to show that the activity of cytochrome P-450 is closely related with smooth surfaced endoplasmic reticulum of the Clara cells, and naphthalene-induced pulmonary damage is mediated by cytochrome P-450.