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Biomarkers of asbestos-induced lung injury: the influence of fiber characteristics and exposure methodology
Citation:
Kodavanti, U., D. Andrews, M. Schladweiler, J. Cyphert, D. Dodd, AND S. Gavett. Biomarkers of asbestos-induced lung injury: the influence of fiber characteristics and exposure methodology. Presented at American Thoracic Society, May 17 - 22, 2013.
Impact/Purpose:
This study provides information on novel biomarkers of asbestos induced lung injury and the influence of fiber characteristics.
Description:
ATS 2013 Biomarkers of asbestos-induced lung injury: the influence of fiber characteristics and exposure methodology Urmila P Kodavanti, Debora Andrews, Mette C Schaldweiler, Jaime M Cyphert, Darol E Dodd, and Stephen H Gavett NHEERL, U.S. EPA, Research Triangle Park, NC; NIEHS, Research Triangle Park, NC; The Hamner Institutes for Health Sciences, Research Triangle Park, NC We recently showed that intratracheal (IT) instillation of Libby amphibole (LA) increases circulating acute phase proteins and inflammatory biomarkers in rats. This study was designed 1) to compare changes in the biomarkers in rats after IT instillation of different naturally occurring asbestos samples including LA, Sumas Mountain chrysotile (SM), El Dorado Hills tremolite (ED) and Ontario actinolite/ferroactinolite cleavage fragments (ON), and 2) to examine biomarkers after subchronic LA or amosite inhalation exposure. Rat-respirable fractions (aerodynamic diameter approximately 2.5 μm) prepared by water elutriation were delivered via a single IT instillation at doses of 0.0, 0.5 and 1.5 mg/rat in F344 rats. LA nose-only inhalation exposure was performed at 0.0, 1.0, 3.3 and 10.0 mg/m3 (aerodynamic diameter approximately 1 μm), and amosite at 3.3 mg/m3, 6h/dayx5d/weekx13 weeks in F344 rats. Inflammation, metabolic syndrome and cancer biomarkers were analyzed in the serum 1 day, 3 months and 15 months post-IT and 1 day, 1 month, and 3 months post subchronic inhalation. IT instillation of all asbestos materials markedly increased serum levels of acute phase proteins (-2 macroglobulin and acid glycoprotein) but to a varying degree based on the degree of acute lung injury induced by each fiber sample (SM=LA>ON=ED). Immediately after (1 day) subchronic inhalation exposure, -2 macroglobulin did not increase but acid glycoprotein increased with the high concentration of LA. Circulating IL-6 levels did not increase with any fiber exposure. However, TNF- levels were slightly, but variably, increased at 3 months and 15 months after IT instillation of asbestos materials (SM>LA=ON=ED). Osteopontin inly slightly increased in rats instilled with SM. Leptin appeared to decrease with IT instillation of all asbestos materials at 3 months, but adiponectin levels did not change. Neither adiponectin nor leptin levels changed after subchronic LA inhalation. Age-related increases in leptin and decreases in adiponectin were noted in control rats instilled with vehicle at 15 months. IT exposure to SM, ON or ED samples was associated with increased circulating insulin at 15 months. This increase was not noted post LA inhalation for up to 3 months. In general, acute changes in the biomarkers after a single bolus IT instillation of LA were more pronounced than those occur after subchronic inhalation exposure. These data suggest that the lung injury induced by various types of asbestos materials may be associated with acute systemic metabolic responses, and potentially increase the risk of developing chronic systemic inflammation and related metabolic syndrome later in life. (This abstract does not represent U.S. EPA policy).