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J Toxicol Environ Health A. 2011;74(14):887-902. doi: 10.1080/15287394.2011.573719.

Interactive effect of cigarette smoke extract and world trade center dust particles on airway cell cytotoxicity.

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  • 1Columbia University, New York, New York, USA.

Abstract

Rescue workers and residents exposed to the environment surrounding the collapse of the World Trade Center (WTC) on September 11, 2001, have suffered a disproportionate incidence of chronic lung disease attributed to the inhalation of airborne dust. To date, the pathophysiology of this lung disease is poorly understood. The aim of this study was to examine whether airborne dust contaminants recovered from the surrounding area 24-48 h after the collapse of the WTC demonstrate direct cytotoxicity to two airway cell types that were most directly exposed to inhaled dust, airway epithelial and smooth muscle cells. It was also of interest to determine whether the presence of these dusts could modulate the effects of cigarette smoke on these cell types in that some of the individuals who responded to the collapse site were also smokers. Human cultured airway epithelial (BEAS-2B) cells were exposed to 10% cigarette smoke extract (CSE), WTC dust particles (10-53 μm; 0.01-0.5 μg/μl), or a combination of the two for 2-24 h. Cell viability was measured by determining mitochondrial integrity (MTT assays) and apoptosis (poly-ADP-ribose polymerase [PARP] immunoblotting). Conditioned cell culture media recovered from the CSE- and/or WTC dust-exposed BEAS-2B cells were then applied to cultured human airway smooth muscle cells that were subsequently assayed for mitochondrial integrity and their ability to synthesize cyclic AMP (a regulator of airway smooth muscle constriction). BEAS-2B cells underwent necrotic cell death following exposure to WTC dust or CSE for 2-24 h without evidence of apoptosis. Smooth muscle cells demonstrated cellular toxicity and enhanced cyclic AMP synthesis following exposure to conditioned media from WTC- or CSE-exposed epithelial cells. These acute toxicity assays of WTC dust and CSE offer insights into lung cell toxicity that may contribute to the pathophysiology of chronic lung disease in workers and residents exposed to WTC dust. These studies clearly showed that WTC dust (at least the supercoarse particle fraction) or CSE alone exerted direct adverse effects on airway epithelial and smooth muscle cells, and altered the signaling properties of airway smooth muscle cells. In addition the combination of CSE and WTC exerted an interactive effect on cell toxicity. It remains to be determined whether these initial cell death events might account, in part, for the chronic lung effects associated with WTC dust exposure among First Responders and others.

PMID:
21623534
[PubMed - indexed for MEDLINE]
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