Proliferative responses of rat nasal epithelia to ozone.

The epithelium of the female Fischer 344/N rat anterior nasal cavity was examined and found to be composed of four types of epithelia: squamous, ciliated respiratory, nonciliated cuboidal/transitional, and olfactory. DNA replication in these tissues was monitored by bromodeoxyuridine (BrdUrd) incorporation. Labeled cells were identified using a monoclonal antibody recognizing BrdUrd. Ciliated respiratory, nonciliated cuboidal/transitional, and olfactory epithelia from control animals had a low level of DNA replication (1 labeled cell/mm basal lamina); in contrast, the squamous epithelium contained 40 labeled cells per millimeter basal lamina. Female Fischer 344/N rats were exposed to 0.0, 0.12, 0.27, or 0.8 ppm ozone, 6 hr/day for up to 7 days. Observations were made after 3 or 7 days of exposure and after 3 or 7 days of recovery from the 7-day exposure. Following exposure to 0.8 ppm ozone, a transient but marked increase in DNA replication was seen in the nonciliated cuboidal/transitional, while in ciliated respiratory and olfactory epithelia the transient increase in DNA replication was less marked. This increase was prominent after 3 days of exposure and absent by 7 days of exposure in all but the cuboidal/transitional epithelium. Exposure to 0.8 ppm ozone for either 3 or 7 days resulted in hyperplasia of the cuboidal epithelium. A depressed level of DNA replication was seen in the squamous epithelium following 7 days of recovery from 7 days of ozone exposure to 0.8 ppm ozone. This study shows that there are regional differences in DNA replication within the anterior nasal epithelium of the rat and that these levels are modulated by exposure to irritants. The cuboidal/transitional epithelium was the most responsive epithelial cell type to the effects of ozone exposure and may, therefore, provide a sensitive indicator of irritant damage to the respiratory tract.