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

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.