title: Toxic effects following phosgene exposure of human epithelial lung cells in vitro using a CULTEX® system.
abstract: The aim of the present study was to investigate toxic effects following phosgene exposure of human epithelial lung cells (A549) in vitro using a CULTEX® system. In particular, toxic effects regarding early biomarkers emerging during the latency period following exposure might be of great value for medical treatment. Cells cultured on semi-permeable membranes were directly exposed at the liquid-air interface to different concentrations of phosgene, or dry medical air. Cell membrane integrity (leakage of LDH), metabolic activity (reduction of Alamar Blue), oxidative damage (GSH, and HO-1, in cell lysates), and release of IL-8, were studied. For most of the above-mentioned biological end-point markers, significant changes could be assessed following a 20 min exposure to 1.0 ppm and 2.0 ppm phosgene. Moreover, except for IL-8, all biological marker profiles showed to be in line with results obtained by others in animal studies. The C×t value of 40 ppm min appeared to be constant. The overall results suggest that at 4 h post-exposure a maximal level of toxicity was achieved. Our results demonstrate the suitability of a CULTEX® system to detect toxic effects induced by phosgene on human epithelial lung cells, which may contribute to the discovery of early biomarkers for new medical countermeasures.
authors.affiliation: TNO Defence, Security and Safety, Business Unit Biological and Chemical Protection, P.O. Box 45, 2280 AA Rijswijk, The Netherlands.
authors.forename: Dorien
authors.initials: D
authors.lastname: Wijte
authors.forename: Marcel J
authors.initials: MJ
authors.lastname: Alblas
authors.forename: Daan
authors.initials: D
authors.lastname: Noort
authors.forename: Jan P
authors.initials: JP
authors.lastname: Langenberg
authors.forename: Herman P M
authors.initials: HP
authors.lastname: van Helden
mesh_terms: D001273:Atmosphere Exposure Chambers; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology; D018384:Oxidative Stress / Q000187:drug effects; D010705:Phosgene / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D002619:Chemical Warfare Agents; D016209:Interleukin-8; D010705:Phosgene; D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1; D005978:Glutathione