Regional increases in rat nasal epithelial cell proliferation following acute and subchronic inhalation of formaldehyde.
Short-term studies (9 days) in the rat have demonstrated that formaldehyde-induced nasal epithelial lesions are associated with increases in surface epithelial cell proliferation rates. The present studies were designed, in part, to investigate cell proliferation rates in the nasal epithelium of rats exposed to formaldehyde for a longer duration in order to determine if correlations exist between (1) the concentration-response in cell proliferation rate with the previously published formaldehyde bioassay tumor response; (2) sites of increased cell proliferation and the regions of the nasal passages that exhibit formaldehyde-induced cytotoxicity; and (3) sites of increased cell proliferation and the regions of the rat nasal passages previously determined to be most susceptible to neoplasia (i.e., the lateral meatus and nasal septum of the anterior nasal passages). Another important endpoint of this study was to provide data for a comparison of formaldehyde-induced responses in rats with previous findings in rhesus monkeys. Fischer-344 rats were exposed to 0, 0.7, 2, 6, 10, or 15 ppm formaldehyde for up to 6 weeks and pulse labeled with tritiated thymidine prior to each scheduled termination. Exposure to formaldehyde at 6 ppm or higher induced site-specific lesions in the nasal respiratory epithelium and was associated with increases in cell proliferation rate which remained statistically elevated throughout the 6 weeks. While a direct correlation between sites susceptible to formaldehyde-induced nasal cancer and increased cell proliferation was not evident, results from the present studies did demonstrate a clear correlation between sites of cellular injury and increases in cell proliferation and a concentration-dependent response which correlated with the previously published formaldehyde bioassay tumor response. Furthermore, this work demonstrated that formaldehyde-induced responses in rats exposed to 6 ppm were morphologically similar to those reported in the rhesus monkey; however, the distribution of lesions between the two species differed significantly.
Monticello
T M
TM
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.
Miller
F J
FJ
Morgan
K T
KT
D000280:Administration, Inhalation; D000818:Animals; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity*; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology; D009300:Nasal Septum; D051381:Rats; D011916:Rats, Inbred F344; D014420:Turbinates
D005557:Formaldehyde