Carbon nanotube exposure caused induction of oxidative stress, pulmonary injury and fibrosis.
Shvedova-A; Kisin-E; Murray-A; Schwegler-Berry-D; Castranova-V; Kagan-VE; Tyurina-Y
Free Radical Res 2006; 40(Suppl 1):S114
Single-walled carbon nanotubes (SWCNT) are new members of carbon allotropes with potentially broad range of revolutionary applications. Unprocessed SWCNT could become airborne and potentially reach lungs. Yet their pulmonary toxicity remains poorly characterized. Pharyngeal 'aspiration of SWCNT elicited unusual pulmonary effects in CS7BU6 mice that combined a robust but acute inflammation with early onset yet progressive fibrosis. A dose-dependent increase in the protein, lactate dehydrogenase (LDH), and g-glutamyl transferase (GGT) activities in BAL were found along with accumulation of 4-hydroxynonena! (oxidative biomarker); and depletion of glutathione in lungs. An early neutrophils accumulation (day 1), followed by lymphocyte (day 3) and macrophage (day 7) influx were accompanied by early elevation of proinflammatory cytokines (TNF-alpha, IL-1b, day 1) followed by fibrogenic TGF-b1 (peaked on day 7). A rapid progressive fibrosis found in mice exhibited two distinct morphologies: (1) SWCNT-induced granulomas mainly associated with hypertrophied epithelial cells surrounding SWCNT aggregates and (2) diffuse interstitial fibrosis and alveolar wall thickening likely associated with dispersed SWCNT. In vitro exposure of murine RAW264.7 macrophages to SWCNT triggered TGF-b1 production similarly to zymosan but generated less TNF-alpha and IL-1b. SWCNT did not cause superoxide or NO* production, active SWCNT engulfment, or apoptosis in RAW264.7 macrophages.
Air-quality-measurement; Air-quality-monitoring; Pulmonary-disorders; Pulmonary-function; Breathing; Stress; Fibrosis; Fibrogenesis; Respiratory-system-disorders; Pulmonary-system-disorders; Nanotechnology
NIOSH, Pathol & Physiol Res Branch, CDC, Morgantown, WV
Free Radical Research