title: Size effects of single-walled carbon nanotubes on in vivo and in vitro pulmonary toxicity.
abstract: To elucidate the effect of size on the pulmonary toxicity of single-wall carbon nanotubes (SWCNTs), we prepared two types of dispersed SWCNTs, namely relatively thin bundles with short linear shapes (CNT-1) and thick bundles with long linear shapes (CNT-2), and conducted rat intratracheal instillation tests and in vitro cell-based assays using NR8383 rat alveolar macrophages. Total protein levels, MIP-1α expression, cell counts in BALF, and histopathological examinations revealed that CNT-1 caused pulmonary inflammation and slower recovery and that CNT-2 elicited acute lung inflammation shortly after their instillation. Comprehensive gene expression analysis confirmed that CNT-1-induced genes were strongly associated with inflammatory responses, cell proliferation, and immune system processes at 7 or 30 d post-instillation. Numerous genes were significantly upregulated or downregulated by CNT-2 at 1 d post-instillation. In vitro assays demonstrated that CNT-1 and CNT-2 SWCNTs were phagocytized by NR8383 cells. CNT-2 treatment induced cell growth inhibition, reactive oxygen species production, MIP-1α expression, and several genes involved in response to stimulus, whereas CNT-1 treatment did not exert a significant impact in these regards. These results suggest that SWCNTs formed as relatively thin bundles with short linear shapes elicited delayed pulmonary inflammation with slower recovery. In contrast, SWCNTs with a relatively thick bundle and long linear shapes sensitively induced cellular responses in alveolar macrophages and elicited acute lung inflammation shortly after inhalation. We conclude that the pulmonary toxicity of SWCNTs is closely associated with the size of the bundles. These physical parameters are useful for risk assessment and management of SWCNTs.
authors: Research Institute of Science for Safety and Sustainability (RISS), National Institute of Advanced Industrial Science and Technology (AIST) , Tsukuba, Ibaraki , Japan .
authors: Katsuhide
authors: K
authors: Fujita
authors: Makiko
authors: M
authors: Fukuda
authors: Shigehisa
authors: S
authors: Endoh
authors: Junko
authors: J
authors: Maru
authors: Haruhisa
authors: H
authors: Kato
authors: Ayako
authors: A
authors: Nakamura
authors: Naohide
authors: N
authors: Shinohara
authors: Kanako
authors: K
authors: Uchino
authors: Kazumasa
authors: K
authors: Honda
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D002460:Cell Line; D054405:Chemokine CCL3 / Q000276:immunology; D020869:Gene Expression Profiling; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D037742:Nanotubes, Carbon / Q000633:toxicity*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000276:immunology
chemical_list: D054405:Chemokine CCL3; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species
keywords: Alveolar macrophages; gene expression profiles; in vitro; in vivo; intratracheal instillation; single-wall carbon nanotubes