Airway epithelial labeling index as an indicator of ozone induced lung injury

Rats were implanted subcutaneously with a bromodeoxyuridine-filled minipump and then were exposed to ozone delivered at a low dose rate (0.4 ppm during 12 h per night) or at a high dose rate (0.8 ppm during 6 h per night). Three and 7 days after pump implantation the cumulative labeling indices were measured in the alveolar zone and in the airways. Greater alveolar labeling indices were observed 7 days after implantation of the minipumps than after 3 days in all groups, but no ozone-related changes were found in the alveoli of rats in either experimental group at either time. After 3 or 7 days, the labeling index in the large intrapulmonary airways and in the terminal bronchioli of the rats exposed to the higher dose rate (0.8 ppm) was increased. In rats exposed to the lower dose rate (0.4 ppm) the labeling index was significantly elevated in the terminal bronchioli after 3 days and in both the terminal bronchioli and large intrapulmonary airways after 7 days. In the terminal bronchioli the extent of cell proliferation appeared to be defined by dose rate rather than by cumulative exposure. It is concluded that measurement of the airway labeling index is a sensitive indicator of the response of the rat lung to acute exposure to ozone.