OZONE-INDUCED ALTERATIONS IN GLUTATHIONE IN LUNG SUBCOMPARTMENTS OF RATS AND MONKEYS

The current studies were designed to test two hypotheses: (1) differen ces in steady-state reduced glutathione levels are responsible for sub compartment differences in susceptibility to acute ozone injury, and ( 2) elevation of reduced glutathione concentrations accounts for the to lerance to further injury produced by repeated ozone exposure. Glutath ione was measured in well-defined subcompartments of the lung of both rats and monkeys to compare alterations occurring in both target (dist al trachea and terminal bronchiole) and nontarget areas (lobar bronchu s, major daughter, minor daughter bronchus, and parenchyma) of the lun g in species that differ in sensitivity to ozone exposure (rat is less susceptible than monkey). Glutathione concentrations were decreased i n trachea of rats exposed to 0.4 ppm ozone for 2 h and increased in lo bar bronchus and distal bronchiole after 2 h exposure at 1 ppm. In mon key, glutathione levels in most subcompartments were not altered by ei ther 0.4 or 1.0 ppm ozone exposure for 2 h. The exceptions were the ma jor daughter subcompartment (200% of control at 0.4 ppm exposure) and the distal bronchiole (55% of control at 1 ppm exposure). Ninety day o zone exposures (6 h/day x 5 days/week) in rats produced an elevation i n glutathione (164% of control value) only in distal bronchiole at the 1 ppm exposure level. In a similar manner, glutathione levels in the distal bronchiole of monkeys exposed for 90 days to 1 ppm O-3 were 165 % of the corresponding control values. These results suggest the follo wing: glutathione levels in target and nontarget areas of the lung and in susceptible versus less susceptible species are not the primary de terminant in the differences observed in ozone toxicity; the response of lung subcompartments to short-term ozone exposure varied depending on airway subcompartment and species; increased glutathione levels may be one reason for adaptation of some airway epithelial cells from rat s and monkeys exposed to O-3 for long periods; and use of well-defined segments of the lung provides a means of assessing changes in target areas of the lung without dilution from nontarget areas.