title: Toxic response of HIPCO single-walled carbon nanotubes in mice and RAW264.7 macrophage cells.
abstract: In this study, we identified the toxic response of pristine single-walled carbon nanotubes (P-SWCNTs) synthesized by HIPCO method in mice and RAW264.7 cells, a murine peritoneal macrophage cell line. P-SWCNT contained a large amount of Fe ion (36 wt%). In the lungs of mice 24 h after intratracheal administration, P-SWCNTs increased the secretion of IL-6 and MCP-1, and the number of total cells, the portion of neutrophils, lymphocytes, and eosinophils, also significantly increased at a 100 μg/mL of concentration. In RAW264.7 cells, cell viability and ATP production decreased in a dose-dependent manner at 24 h after exposure, whereas the generations of ROS and NO were enhanced at all concentrations together with the activation of the MAP kinase pathway. Moreover, the levels of both apoptosis- and autophagy-related proteins and ER stress-related proteins clearly increased, and the concentrations of Fe, Cu, and Zn ions, but not of Mn ions, increased in a dose-dependent manner. TEM images also revealed that P-SWCNTs induced the formation of autophagosome-like vacuoles, the dilatation of the ER, the generation of mitochondrial flocculent densities, and the separation of organelle by disappearance of the cell membrane. Taken together, we suggest that P-SWCNTs cause acute inflammatory response in the lungs of mice, and induce autophagy accompanied with apoptosis through mitochondrial dysfunction and ER stress in RAW264.7 cells. Furthermore, further study is required to elucidate how the physicochemical properties of SWCNTs determine the cell death pathway and an immune response.
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea. Electronic address: pejtoxic@hanmail.net.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Nur Elida M
authors.initials: NE
authors.lastname: Zahari
authors.affiliation: Inhalation Toxicology Center, Korea Institute of Toxicology, Jeongeup 580-185, Republic of Korea.
authors.forename: Min-Sung
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Inhalation Toxicology Center, Korea Institute of Toxicology, Jeongeup 580-185, Republic of Korea.
authors.forename: Sang jin
authors.initials: Sj
authors.lastname: Lee
authors.affiliation: Inhalation Toxicology Center, Korea Institute of Toxicology, Jeongeup 580-185, Republic of Korea.
authors.forename: Kyuhong
authors.initials: K
authors.lastname: Lee
authors.affiliation: Toxicologic Pathology Center, Korea Institute of Toxicology, Daejeon, Republic of Korea.
authors.forename: Byoung-Seok
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Seoul Center, Korea Basic Science Institute, Seoul 126-16, Republic of Korea.
authors.forename: Cheolho
authors.initials: C
authors.lastname: Yoon
authors.affiliation: College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.affiliation: Department of Chemical Engineering, Kwangwoon University, Seoul 139-701, Republic of Korea.
authors.forename: Younghun
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea. Electronic address: jhkim@ajou.ac.kr.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016207:Cytokines; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase
keywords: Apoptosis; Autophagy; ER stress; Macrophages; Mitochondria; SWCNT