Effect of Cumulative Ozone Exposure on Ozone-Induced Nasal Epithelial Hyperplasia and Secretory Metaplasia in Rats

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Abstract
Repeated exposure of rats to O3 induces proliferative and secretory metaplastic changes within nasal airway epithelia that may protect against subsequent exposures. Our study assessed the effect of different cumulative exposure times on O3-induced nasal epithelial hyperplasia and secretory metaplasia. Rats were exposed 6 h/day to air or to 0.8 ppm O3 and were sacrificed 18 h after the end of their last exposure. The rats were exposed to either air or 0.8 ppm O3 for 3 or 7 days, or to 0.8 ppm O3 for 3 days followed by a 4-day exposure to air. The effects of the exposures were determined by quantitating the hyperplastic (epithelial nuclei/mm basal lamina) and secretory metaplastic changes (volume densities of acidic and neutral mucosubstances) within the nasal nonciliated cuboidal epithelium (NNCE). There were no significant changes in NNCE cell numeric density, or in the volume density of intraepithelial mucus, compared to air-exposed control rats, in rats exposed to O3 for 3 days and sacrificed 18 h later. Compared to control rats, there was significant epithelial hyperplasia and secretory metaplasia within the NNCE of rats exposed to O3 either for 7 days or for 3 days followed by 4 days of exposure to air. There were no significant differences in NNCE cell hyperplasia or secretory metaplasia between these two experimental groups. Three 6 h/day exposures to 0.8 ppm O3 triggered hyperplastic and metaplastic changes within rat NNCE that were indistinguishable from those produced by seven 6 h/day exposures to the same concentration of O3. The data suggest that O3 is capable of rapidly inducing hyperplastic and metaplastic responses within rat NNCE, and that once initiated, development of the phenotypic changes within the epithelium does not require further O3 exposure.