US EPA

3085390 

Journal Article 

Abstract 

Inflammatory and oxidative stress response associated with in vitro exposure of cultured human bronchial epithelial cells to different size fractions of Libby-type Amphibole and amosite asbestos 

Duncan, KE; Dailey, LA; Ghio, AJ; Bern, AM; Lowers, HA; Meeker, GP; Padilla-Carlin, DJ; Devlin, RB 

2010 

Yes 

American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 

181 

A1148 

English 

10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A1148 

WOS:000208771000149 

is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans

RATIONALE: Recent studies have shown an increase in asbestos-related mortality and pulmonary disease in residents of Libby, Montana exposed to asbestos-contaminated vermiculite. This study compares the mechanisms by which Libby-type Amphibole (LA) stimulates production of mediators involved in pulmonary disease to a well-characterized asbestos (amosite). Insight into the mode of action of these two amphibole samples was obtained by measuring changes in toxicity pathways of cultured human bronchial epithelial cells (HBECs) exposed to the asbestos materials.

METHODS: Water elutriation was used to prepare size-fractionated samples of amosite and LA in order to compare the toxicity and modes of action of each size fraction. This abstract focuses on comparison of the smallest size fraction (MMAD ≤ 2.5 µm) with unfractionated asbestos. Primary HBECs were exposed to different doses (2.64, 13.2, 26.4 µg/cm^2) of amosite or LA asbestos for 2 or 24 hrs and changes in mRNA transcript levels coding for inflammatory and oxidative stress markers were evaluated by Real Time (RT)-PCR.

RESULTS: A dose-response for IL-8 was observed for both amosite and LA after 24 hr for all size fractions. Unfractionated amosite and LA stimulated equivalent increases in IL-8 mRNA (50- and 46-fold, respectively compared to control), at a dose of 26.4 µg/cm^2. However, at the same mass dose, size-fractionated amosite was ~4x as potent as LA (123- and 33-fold increases in IL-8 mRNA, respectively). Similar changes were observed for COX-2 mRNAs. Expression of the RT-PCR data in terms of total surface area measured by gas adsorption cannot account for the observed difference in response (9.0 versus 12.9 m^2/g for amosite and LA, respectively). All fractions of amosite and LA induced an equal, yet small increase in HO-1 mRNA after 24 hr (~3-4-fold). Generation of oxidants by the size-fractionated samples measured by thiobarbituric acid-reactive products of deoxyribose showed a ~2-fold increase in oxidant production for amosite compared with LA. This oxidant generation was inhibited by the addition of a free radical scavenger or iron chelator.

CONCLUSIONS: The unfractionated amosite and LA are equally potent at inducing inflammation in HBECs, however the smaller size fraction of amosite is ~4x more potent than LA on a mass basis. Surface area and oxidant generation do not appear to account for these observed differences. Efforts are being directed at elucidating the mechanism of toxicity for the smaller size fractions. This proposed abstract does not necessarily reflect EPA policy. 

American Thoracic Society 2010 International Conference 

New Orleans, LA 

May 14-19, 2010