ENDOTOXIN POTENTIATES OZONE-INDUCED MUCOUS CELL METAPLASIA IN RAT NASAL EPITHELIUM

People are exposed to a combination of environmental pollutants throug hout their lives. Repeated exposures of one common pollutant, ozone, h ave been reported to cause the development of mucous cell metaplasia i n the nasal transitional epithelium (NTE) of rats. The present study w as designed to test the hypothesis that exposure to bacterial endotoxi n, another toxicant ubiquitous to the environment, potentiates this me taplastic response in rat NTE, Rats were exposed to 0 or 0.5 ppm ozone 8 h/day for 3 days. After ozone exposure, rats were intranasally inst illed with saline containing 0 or 100 mu g/ml endotoxin once daily for 2 days. Rats were killed 6 h or 3 days after the last intranasal inst illation, Nasal tissue was processed for light microscopy and image an alysis, or for isolation of total RNA. Mucous cell metaplasia was not detected in air/endotoxin-exposed rats, was observed in ozone/saline-e xposed rats, and was most severe in ozone/endotoxin-exposed rats. At 6 h after instillation, amounts of intraepithelial mucosubstances (IM) were 4-fold greater in NTE of ozone/endotoxin-exposed rats as compared to controls. These IR? levels were similar to those of ozone/saline-e xposed rats. Mucin-specific mRNA (rMuc-5AC) levels were elevated in al l treatment groups at this timepoint, At 3 days after instillation, am ounts of IM in ozone/endotoxin-exposed rats were 10-fold greater than in controls and 5-fold greater than in ozone/saline-exposed rats. rMuc -5AC mRNA levels remained elevated in the ozone/endotoxin-exposed rats . Despite the fact that bacterial endotoxin alone does not cause a phe notypic change in rat NTE, it can augment the mucous cell metaplasia i nduced by a previous exposure to ozone. (C) 1998 Academic Press.