BIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES IN NASAL EPITHELIUM OF RATSAFTER 3-DAY INTERMITTENT EXPOSURE TO FORMALDEHYDE AND OZONE ALONE OR IN COMBINATION
Fr. Cassee et Vj. Feron, BIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES IN NASAL EPITHELIUM OF RATSAFTER 3-DAY INTERMITTENT EXPOSURE TO FORMALDEHYDE AND OZONE ALONE OR IN COMBINATION, Toxicology letters, 72(1-3), 1994, pp. 257-268
To get a better insight into the pathophysiology of the nasal changes
induced by formaldehyde-ozone mixtures, a 3-day inhalation study was c
arried out in rats, using intermittent exposure to formaldehyde (3.6 p
pm) and ozone (0.4 ppm) alone or in combination and focusing on bioche
mical and histopathological changes in rat nasal respiratory epitheliu
m. Formaldehyde dehydrogenase, glutathione S-transferase, glutathione
reductase, and glucose-6-phosphate dehydrogenase activities in this ep
ithelium were not affected by the individual compounds. However, combi
ned exposure to formaldehyde and ozone resulted in slightly decreased
activities of these enzymes. Formaldehyde was found to induce rhinitis
, degeneration, frank necrosis, hyperplasia and squamous metaplasia of
the ciliated and non-ciliated nasal respiratory epithelium, while ozo
ne induced disarrangement, flattening and slight basal cell hyperplasi
a of the non-ciliated cuboidal epithelium accompanied by influx of neu
trophils. Proliferating cell nuclear antigen (PCNA) expression was ele
vated not only in nasal areas showing ozone-induced histopathological
changes but also in the otherwise normal-appearing epithelium of the n
asal septum. No interactive effects were found with respect to prolife
rative response of the nasal respiratory epithelium after exposure to
the formaldehyde-ozone mixture. The present study did not provide evid
ence of a major role of glutathione and glutathione-dependent enzymes
in the pathogenesis of nasal lesions induced by formaldehyde and/or oz
one, demonstrated the potential of ozone to affect the mucociliary epi
thelium lining the nasal septum, and suggested that PCNA expression is
a sensitive tool for detection of early effects of respiratory irrita
nts.