PNNL

Abstract

Reflecting their exceptional potential to advance a range of biomedical, aeronautic, and other industrial products, carbon nanotube (CNT) production, and the potential for human exposure to aerosolized CNT’s, is increasing. CNT’s have toxicologically significant structural and chemical similarities to asbestos, and have repeatedly been shown to cause pulmonary inflammation, granuloma formation and fibrosis after inhalation/instillation/aspiration exposure in rodents, a pattern of effects similar to those observed following exposure to asbestos. To determine the degree to which responses to SWCNT and asbestos are similar or different, the pulmonary response of C57BL/6 mice to repeated exposure to SWCNT, crocidolite asbestos and ultrafine carbon black (UFCB) were compared using high-throughput global HPLC-FTICR-MS proteomics, histopathology and BAL cytokine analyses. Mice were exposed to material suspensions (40 µg/mouse) twice a week, for 3 weeks by pharyngeal aspiration. Histologically, the incidence and severity of inflammatory and fibrotic responses were greatest in mice treated with SWCNT. SWCNT treatment affected the greatest changes in abundance of identified lung tissue proteins. The trend in number of proteins affected (SWCNT (376)>asbestos (231)>UFCB (184)) followed the potency of these materials in 3 biochemical assays of inflammation (cytokines). SWCNT treatment uniquely affected the abundance of 109 proteins, but these proteins largely represent cellular processes affected by asbestos treatment as well, further evidence of broad similarity in the tissue-level response to asbestos and SWCNT. Two high sensitivity markers of inflammation, one (S100a9) observed in humans exposed to asbestos, were found and may be promising biomarkers of human response to SWCNT exposure.