Comparing the Toxicological Responses of Pulmonary Air-Liquid Interface Models upon Exposure to Differentially Treated Carbon Fibers

比较肺部气液界面模型暴露于经不同处理的碳纤维时的毒理学反应

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作者:Alexandra Friesen, Susanne Fritsch-Decker, Sonja Mülhopt, Caroline Quarz, Jonathan Mahl, Werner Baumann, Manuela Hauser, Manuela Wexler, Christoph Schlager, Bastian Gutmann, Tobias Krebs, Ann-Kathrin Goßmann, Frederik Weis, Matthias Hufnagel, Dieter Stapf, Andrea Hartwig, Carsten Weiss

Abstract

In recent years, the use of carbon fibers (CFs) in various sectors of industry has been increasing. Despite the similarity of CF degradation products to other toxicologically relevant materials such as asbestos fibers and carbon nanotubes, a detailed toxicological evaluation of this class of material has yet to be performed. In this work, we exposed advanced air-liquid interface cell culture models of the human lung to CF. To simulate different stresses applied to CF throughout their life cycle, they were either mechanically (mCF) or thermo-mechanically pre-treated (tmCF). Different aspects of inhalation toxicity as well as their possible time-dependency were monitored. mCFs were found to induce a moderate inflammatory response, whereas tmCF elicited stronger inflammatory as well as apoptotic effects. Furthermore, thermal treatment changed the surface properties of the CF resulting in a presumed adhesion of the cells to the fiber fragments and subsequent cell loss. Triple-cultures encompassing epithelial, macrophage, and fibroblast cells stood out with an exceptionally high inflammatory response. Only a weak genotoxic effect was detected in the form of DNA strand breaks in mono- and co-cultures, with triple-cultures presenting a possible secondary genotoxicity. This work establishes CF fragments as a potentially harmful material and emphasizes the necessity of further toxicological assessment of existing and upcoming advanced CF-containing materials.

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