Toxicological Sciences, Vol 51, 135-145, Copyright © 1999 by Society of Toxicology
HY Cho, JA Hotchkiss and JR Harkema
Rats repeatedly exposed to high ambient concentrations of ozone develop
mucous cell metaplasia (MCM) in the nasal transitional epithelium (NTE).
The present study was designed to determine the temporal relationships of
ozone-induced inflammatory and epithelial responses and their correlation
with subsequent MCM in the NTE of rats. Male F344/N rats were exposed to
0.5 ppm ozone, 8 h/day for 1, 2, or 3 days. Two h prior to sacrifice, all
the rats were injected intraperitoneally with 5'-bromo-2-deoxyuridine
(BrdU) to label epithelial cells undergoing DNA synthesis. Rats exposed to
ozone for 1 or 2 days were killed 2 h after the exposure. Rats exposed to
ozone for 3 days were killed 2 h or 1, 2, or 4 days after the exposure.
Control rats were killed after a 7-day exposure to filtered air. One nasal
passage from the anterior nasal cavity of each rat was fixed and processed
for light microscopy to morphometrically determine the numeric densities of
epithelial cells, neutrophils, and mucous cells, and the amount of
intraepithelial mucosubstances in the NTE. The maxilloturbinate from the
other nasal passage was processed for analysis of an airway mucin- specific
gene (i.e., rMuc-5AC mRNA). Acute ozone exposure induced a rapid increase
in rMuc-5AC mRNA levels prior to the onset of MCM, and the increased levels
of rMuc-5AC mRNA persisted with MCM. Neutrophilic inflammation coincided
with epithelial DNA synthesis and upregulation of rMuc-5AC, but was
resolved when MCM first appeared in the NTE. The results of the present
study suggest that upregulation of mucin mRNA by acute ozone exposure may
be associated with the concurrent neutrophilic inflammation and epithelial
hyperplasia in the NTE. Ozone-induced MCM may be dependent on these
important pre-metaplastic responses (i.e., mucin mRNA upregulation,
neutrophilic inflammation, and epithelial proliferation).
ARTICLES
Inflammatory and epithelial responses during the development of ozone- induced mucous cell metaplasia in the nasal epithelium of rats
Department of Pharmacology and Toxicology, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA.
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