Journal Article

Effect of Size Fractionation on the Toxicity of Amosite and Libby Amphibole Asbestos

Kelly E. Duncan, Andrew J. Ghio, Lisa A. Dailey, Amy M. Bern, Eugene A. Gibbs-Flournoy, Danielle J. Padilla-Carlin, Victor L. Roggli and Robert B. Devlin

in Toxicological Sciences

Volume 118, issue 2, pages 420-434
Published in print December 2010 | ISSN: 1096-6080
Published online September 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq281
Effect of Size Fractionation on the Toxicity of Amosite and Libby Amphibole Asbestos

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Abnormally high incidences of asbestos-related pulmonary disease have been reported in residents of Libby, Montana, because of occupational and environmental exposure to asbestos-contaminated vermiculite. The mechanism by which Libby amphibole (LA) causes pulmonary injury is not known. The purpose of this study is to compare the cellular stress responses induced in primary human airway epithelial cells (HAECs) exposed to a respirable size fraction (≤ 2.5 μm) of Libby amphibole (LA2.5) to a similar size fraction of a reference amphibole sample amosite (AM2.5). HAEC were exposed to 0, 2.64, 13.2, or 26.4 μg/cm2 AM2.5 or LA2.5 or to equivalent doses of unfractionated amosite (AM) or LA for 2 or 24 h. Comparable messenger RNA transcript levels were observed for interleukin-8, cyclooxygenase-2, and heme oxygenase-1 in HAEC following a 24-h exposure to AM or LA. Conversely, exposure to AM2.5 resulted in a 4- to 10-fold greater induction in these proinflammatory mediators compared with LA2.5 after 24 h. Evaluation of the expression of 84 additional genes involved in cellular stress and toxicity responses confirmed a more robust response for AM2.5 compared with LA2.5 on an equal mass basis. Differences in total surface area (TSA) by gas adsorption, total particle number, or oxidant generation by the size-fractionated particles did not account for the observed difference in response. In summary, AM2.5 and LA2.5 are at least as potent in stimulating production of proinflammatory cytokines as unfractionated AM and LA. Interestingly, AM2.5 was more potent at inducing a proinflammatory response than LA2.5. This difference could not be explained by differences in mineral contamination between the two samples, TSA, or oxidant generation by the samples.

Keywords: Libby amphibole; amosite; size fractionation; inflammation; oxidative stress; airway epithelium

Journal Article.  9973 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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