BIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES IN NASAL EPITHELIUM OF RATSAFTER 3-DAY INTERMITTENT EXPOSURE TO FORMALDEHYDE AND OZONE ALONE OR IN COMBINATION

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.