| The nasal passage is the major or the only means of entry for airborne substances into the respiratory tract in animals. Nasal mucosa contains high metabolic activity for a number of substrates, comparable to or even higher than liver tissue. Therefore, nasal mucosa may be a main target for injury induced by air-pollutant exposure. The purpose of the work described in this dissertation was to examine the effect of exposure to prevalent air-pollutants on the integrity of rat nasal mucosa. The air-pollutants examined here include naphthalene alone and ozone and/or 1-nitronaphthalene. Our results show that regardless of route of exposure, severe injury occurred specifically in rat olfactory mucosa in response to naphthalene. Non-olfactory mucosa, although situated in a well-perfused and high airflow region, metabolized naphthalene slowly and injury was slight. The pattern of olfactory mucosal injury from inhaled naphthalene was different from systemically injected naphthalene. We conclude that in situ naphthalene bioactivation and nasal airflow cause region-specific injury patterns in the nasal mucosa of rats exposed to naphthalene by inhalation. Since olfactory and non-olfactory regions of isolated monkey nasal tissues had a lower rate of microsomal bioactivation of naphthalene than rat olfactory mucosa, we conclude that monkey nasal mucosa is less likely to be a target of naphthalene injury. Lastly, in parallel to previous studies specific to lung tissues, we examined whether previous chronic ozone exposure would alter the susceptibility of rat nasal mucosa to acute toxicity of systemic 1-nitronaphthalene. Our results show that ozone tolerance is characterized by marked goblet cell metaplasia, and nasal goblet cells, whether metaplastic or non-metaplastic, show very little injury from 1-nitronaphthalene. This suggests a protective role of mucosubstances against toxicants. The findings from the air-pollutants examined in this dissertation suggest that rigorous comparative studies of possible toxicity of ambient air-pollutants on nasal mucosa from humans or relevant biological models should follow in the future to better assess species-differences in risk of air-pollutant exposure. |
