Effect of size fractionation on the toxicity of amosite and Libby amphibole asbestos.
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 (LA(2.5)) to a similar size fraction of a reference amphibole sample amosite (AM(2.5)). HAEC were exposed to 0, 2.64, 13.2, or 26.4 μg/cm(2) AM(2.5) or LA(2.5) 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 AM(2.5) resulted in a 4- to 10-fold greater induction in these proinflammatory mediators compared with LA(2.5) after 24 h. Evaluation of the expression of 84 additional genes involved in cellular stress and toxicity responses confirmed a more robust response for AM(2.5) compared with LA(2.5) 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, AM(2.5) and LA(2.5) are at least as potent in stimulating production of proinflammatory cytokines as unfractionated AM and LA. Interestingly, AM(2.5) was more potent at inducing a proinflammatory response than LA(2.5). This difference could not be explained by differences in mineral contamination between the two samples, TSA, or oxidant generation by the samples.
Duncan
Kelly E
KE
Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. keduncan@email.unc.edu
Ghio
Andrew J
AJ
Dailey
Lisa A
LA
Bern
Amy M
AM
Gibbs-Flournoy
Eugene A
EA
Padilla-Carlin
Danielle J
DJ
Roggli
Victor L
VL
Devlin
Robert B
RB
D017639:Asbestos, Amosite / Q000633:toxicity*; D017636:Asbestos, Amphibole / Q000633:toxicity*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism
D017636:Asbestos, Amphibole; D004785:Environmental Pollutants; D018836:Inflammation Mediators; D016209:Interleukin-8; D017639:Asbestos, Amosite; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human