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Khan, M.D.H. ; Klein, D. ; Mossbrugger, I. ; Oesterle, D. ; Csanády, G.A. ; Quintanilla-Martinez, L. ; Filser, J.G.

Is propylene oxide induced cell proliferation in rat nasal respiratory epithelium mediated by a severe depletion of water-soluble non-protein thiol?

Toxicol. Lett. 185, 203-210 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Propylene oxide (PO) concentrations >or=300 ppm induced cell proliferation and tumors in rat nasal respiratory epithelium (NRE). Cell proliferation was suggested to result from depletion of glutathione (GSH) in NRE. In order to substantiate this hypothesis, cell proliferation - measured by bromodeoxyuridine incorporation into DNA of the epithelium lining middle septum, dorsal medial meatus, and medial and lateral surfaces of the nasoturbinate in transverse nasal sections taken immediately posterior to the upper incisor teeth - and water-soluble non-protein thiol (NPSH) in NRE were determined after exposing male Fischer 344 rats to 50 ppm, 100 ppm, 200 ppm, or 300 ppm PO (6 h/day, 3 days). Both parameters were also investigated after treating rats for 3 days with diethylmaleate (DEM; 2 x 250 mg/kg/day or 500 + 150 mg/kg/day) or buthionine sulfoximine (BSO; 500 mg/kg/day). Exposure to 50 ppm PO and treatment with 2 x2 50 mg/kg/day DEM resulted in NPSH levels approximating 50% and 80% of the level in untreated controls, respectively. Cell proliferation did not increase. After exposures to >or= 100 ppm PO or treatment with BSO or 500 + 150 mg/kg/day DEM, NPSH was depleted to
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Propylene oxide; Nasal respiratory epithelium; Cell proliferation; Glutathione; Diethylmaleate; Buthionine sulfoximine; inhaled ethylene-oxide; oxidative stress; f344 rats; glutathione depletion; buthionine sulfoximine; inhalation exposure; hemoglobin add
ISSN (print) / ISBN 0378-4274
e-ISSN 1879-3169
Journal Toxicology Letters
Quellenangaben Volume: 185, Issue: 3, Pages: 203-210 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOXI)
Institute of Pathology (PATH)