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Opposite effects of low and high formaldehyde concentrations on DNA integrity, PGE2-synthesis, proliferation, and intermediate filament expression in human nasal epithelial cells

: Schäfer, D.; Pods, R.; Ziemann, C.

Naunyn-Schmiedebergs archives of pharmacology 369 (2004), Supplement 1, S.R113
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Spring Meeting) <45, 2004, Mainz>
Zeitschriftenaufsatz, Konferenzbeitrag
Fraunhofer ITEM ()

Although formaldehyde (HCHO) may be a key molecule in cell proliferation of biological systems, high concentrations of HCHO in aqueous solution display geno-toxic, carcinogenic, proliferation inhibiting and pro-apoptotic potential. In the respiratory tract, irritant and sensitizing effects of HCHO as well as induction of chronic inflammatory alterations have also been documented. Unfortunately, little is know about the effects of low HCHO concentrations on human respiratory epithelial cells of the nasal cavity. In the present study, primary human nasal epithelial cells (HUNEC) and human nasal carcinoma cells (RPMI-2650) were exposed, as model systems, for Ih to 0.0001-1000µM HCHO to investigate concentration-dependent effects on structural and functional cell parameter. With high HCHO concentrations (>10µM) the expected inhibition of cell proliferation (HUNEC: ~18%, RPMI-2650: ~57%) and formation of DNA-protein cross-links could be demonstrated. In addition, high HCHO concentrations reduced PGE2-synthesis of exposed cells (HUNEC: ~6.7%, RPMI-2650: ~14.7%) and inhibited expression of the intermediate filament cytokeratin 14 (HUNEC: up to ~5%, RPMI-2650 up to ~90%). Interestingly, low HCHO concentrations (<10µM) mediated completely opposite effects. Using the alkaline comet assay, strand break formation was detected in HUNEC and RPMI-2650 cells at 0.001 to 10µM HCHO. PGE2-synthesis, as assessed by competitive EIA, and cell proliferation, assessed by alamarBlue test, were stimulated at low HCHO (<10 µM), with RPMI-2650 cells liberating ~2-fold more PGE2 and exhibiting more enhanced proliferation (~23% versus 8.7% in HUNEC). Immunocyto-chemical determination of cytokeratin 14 demonstrated induction of expression in HUNEC. The present study thus demonstrated opposite effects of low and high HCHO concentrations on human nasal epithelial cells, with alterations at low doses, which might be relevant to various pathological conditions, such as nasal hyper-activity, hypersensitivity, but also carcinogenesis. RPMI-2650 cells reacted similarly, but were markedly more sensitive to HCHO exposure than primary nasal epithelial cells. This might be important in the context of defining suitable nasal epithelial cell culture models for screening purposes.