Toxic effects following phosgene exposure of human epithelial lung cells in vitro using a CULTEX® system.

Toxicology in Vitro(2011)

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摘要
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 (R) 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 x 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 (R) 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. (C) 2011 Elsevier Ltd. All rights reserved.
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关键词
Phosgene,CULTEX®,A549,Toxicity
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