CYTOCHROME-P450 2E1 IN RAT TRACHEOBRONCHIAL AIRWAYS - RESPONSE TO OZONE EXPOSURE

The distal trachea and centriacinus of the lung are primary sites of a cute injury during short-term ozone exposure; long-term exposure yield s cells in these areas that are resistant to high doses of oxidant gas es. Epithelial cells located in primary sites for ozone injury are als o targets for chemicals that undergo cytochrome P450 (CYP)-dependent a ctivation. These studies were designed to compare the effects of ozone exposure on pulmonary CYP2E1 in susceptible and nonsusceptible sites within the airway tree of lung. CYP2E1 activity was measured in well-d efined regions of airways using p-nitrophenol, a CYP2E1-selective subs trate, with HPLC/ electrochemical detection of the p-nitrocatechol, Al terations in distribution of CYP2E1 were evaluated by immunohistochemi stry. CYP2E1 activities were highest in the distal bronchioles and min or daughter airways but were much lower in the lobar bronchi/ major da ughter airways and trachea. Immediately after shortterm ozone exposure s (8 h, 1 ppm), CYP2E1 activities were elevated only in the lobar bron chi/major daughter airways. These activities remained above the filter ed air control at 1 day but returned to control levels by 2 days. Immu nohistochemical assessment of CYP2E1 protein in ozone and filtered air -exposed animals was consistent with the activity measurements. After long-term ozone exposures (90 days, 1 ppm), CYP2E1 activities were dec reased in the major and minor daughter airways. These studies indicate that CYP2E1 activities vary substantially by airway level. However, o zone exposure only results in minimal alterations in activity with var ying concentration of ozone, length of exposure, and time after exposu re in any of the lung subcompartments examined. (C) 1998 Academic Pres s.