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Direct Combination of Nanoparticle Fabrication and Exposure to Lung Cell Cultures in a Closed Setup as a Method To Simulate Accidental Nanoparticle Exposure of Humans

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Barbara Rothen-Rutishauser*^†, Robert N. Grass^‡, Fabian Blank^†, Ludwig K. Limbach^‡, Christian Mühlfeld^†, Christina Brandenberger^†, David O. Raemy^†, Peter Gehr^† and Wendelin J. Stark^‡

Institute of Anatomy, Division of Histology, University of Bern, Bern, Switzerland, and Institute for Chemical and Bioengineering, D-CHAB, ETH Zurich, Zurich, Switzerland

Environ. Sci. Technol., 2009, 43 (7), pp 2634–2640

DOI: 10.1021/es8029347

Publication Date (Web): March 2, 2009

* Corresponding author e-mail: barbara.rothen@ana.unibe.ch; phone: ++41-31-631-8441; fax: ++41-31-631-3807., †

University of Bern.

, ‡

ETH Zurich.

Section:

Toxicology

Abstract

The tremendous application potential of nanosized materials stays in sharp contrast to a growing number of critical reports of their potential toxicity. Applications of in vitro methods to assess nanoparticles are severely limited through difficulties in exposing cells of the respiratory tract directly to airborne engineered nanoparticles. We present a completely new approach to expose lung cells to particles generated in situ by flame spray synthesis. Cerium oxide nanoparticles from a single run were produced and simultaneously exposed to the surface of cultured lung cells inside a glovebox. Separately collected samples were used to measure hydrodynamic particle size distribution, shape, and agglomerate morphology. Cell viability was not impaired by the conditions of the glovebox exposure. The tightness of the lung cell monolayer, the mean total lamellar body volume, and the generation of oxidative DNA damage revealed a dose-dependent cellular response to the airborne engineered nanoparticles. The direct combination of production and exposure allows studying particle toxicity in a simple and reproducible way under environmental conditions.

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