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In vitro determinants of asbestos fiber toxicity: Effect on the relative toxicity of Libby Amphibole in pirmary human airway epithelial cells
Citation:
Duncan, K., Philip M. Cook, S. Gavett, L. Dailey, R. Mahoney, Andy Ghio, V. Roggli, AND R. Devlin. In vitro determinants of asbestos fiber toxicity: Effect on the relative toxicity of Libby Amphibole in pirmary human airway epithelial cells. Particle and Fibre Toxicology. BioMed Central Ltd, London, Uk, 11:2, (2014).
Impact/Purpose:
The composition of Libby amphibole (LA) is complex and minimal toxicity data are available. In this study, we conduct a comparative toxicity analysis of LA compared with standard reference amphibole samples.
Description:
Background An abnormally high incidence of lung disease has been observed in the residents of Libby, Montana, which has been attributed to occupational and environmental exposure to fibrous amphiboles originating from a nearby contaminated vermiculite mine. The composition of Libby amphibole (LA) is complex and minimal toxicity data are available. In this study, we conduct a comparative toxicity analysis of LA compared with standard reference amphibole samples. Methods Primary human airway epithelial cells (HAEC) were exposed for 24 h to increasing doses of two different LA samples, one collected in the year 2000 (LA2000) and one in 2007 (LA2007) as well as standard reference samples of RTI amosite and UICC amosite. Interleukin-8 (IL8) gene expression was quantified by qRT-PCR as a measure of the relative pro-inflammatory response induced in HAEC in response to amphibole particle exposure. We further evaluated the relative contribution of key physicochemical determinants on the observed pro-inflammatory response. Results The RTI amosite sample, which was found to contain the longest fibers, demonstrated the greatest potency at inducing IL8 gene expression in HAEC when evaluated on an equal mass basis. Comparatively, the two LA samples and the UICC amosite sample were found to consist of similar particle numbers per milligram as well as similar particle size distributions and were subsequently found to induce comparable levels of IL8 gene expression. A strong correlation was observed between the alternative dose metrics of ∑ (particle length) and surface area for elongated mineral particles with aspect ratio ≥3:1. Expression of the IL8 data with respect to either of these metrics eliminated the differential response between the RTI amosite sample and the other samples that was observed when HAEC were exposed on an equal mass basis. Conclusions LA is as potent as the UICC amosite reference sample at inducing a pro-inflammatory response in HAEC but is less potent than the RTI amosite sample. The results of this study show that the ∑ (particle length) and surface area are related metrics that contribute significantly to the toxicological potential of these amphibole samples with respect to the inflammogenic response induced in airway epithelial cells.