In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT

MWCNT 肺部炎症致病性和遗传毒性的体内外相关性

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作者:Emilio Di Ianni, Johanna Samulin Erdem, Peter Møller, Nicklas Mønster Sahlgren, Sarah Søs Poulsen, Kristina Bram Knudsen, Shan Zienolddiny, Anne Thoustrup Saber, Håkan Wallin, Ulla Vogel, Nicklas Raun Jacobsen

Background

Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and ethical concerns of animal testing drive a need for in vitro models with predictive power in respiratory toxicity. The

Conclusion

This study shows correlations of pro-inflammatory potential in A549 and THP-1a cells with neutrophil influx in mice, and concordance in genotoxic response between THP-1a cells and BAL cells, for seven MWCNT.

Results

Effective doses were shown to be 25 to 53%, and 21 to 57% of the doses administered to A549 and THP-1a, respectively. In submerged conditions (A549 and THP-1a cells), all NM induced dose-dependent IL-8 expression. NM-401 and NRCWE-006 caused the strongest pro-inflammatory response. In the ALI-exposed co-culture, only NM-401 caused increased IL-8 expression, and no DNA strand breaks were observed. Strong correlations were found between in vitro and in vivo inflammation when doses were normalized by surface area (also proxy for diameter and length). Significantly increased DNA damage was found for all MWCNT in THP-1a cells, and for short MWCNT in A549 cells. A concordance in genotoxicity of 83% was obtained between THP-1a cells and broncho-alveolar lavaged (BAL) cells.

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