Biological toxicity and inflammatory response of semi-single-walled carbon nanotubes.
The toxicological studies on carbon nanotubes (CNTs) have been urgently needed from the emerging diverse applications of CNTs. Physicochemical properties such as shape, diameter, conductance, surface charge and surface chemistry of CNTs gained during manufacturing processes play a key role in the toxicity. In this study, we separated the semi-conductive components of SWCNTs (semi-SWCNTs) and evaluated the toxicity on days 1, 7, 14 and 28 after intratracheal instillation in order to determine the role of conductance. Exposure to semi-SWCNTs significantly increased the growth of mice and significantly decreased the relative ratio of brain weight to body weight. Recruitment of monocytes into the bloodstream increased in a time-dependent manner, and significant hematological changes were observed 28 days after exposure. In the bronchoalveolar lavage (BAL) fluid, secretion of Th2-type cytokines, particularly IL-10, was more predominant than Th1-type cytokines, and expression of regulated on activation normal T cell expressed and secreted (RANTES), p53, transforming growth factor (TGF)-β, and inducible nitric oxide synthase (iNOS) increased in a time-dependent manner. Fibrotic histopathological changes peaked on day 7 and decreased 14 days after exposure. Expression of cyclooxygenase-2 (COX-2), mesothelin, and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) also peaked on day 7, while that of TGF-β peaked on days 7 and 14. Secretion of histamine in BAL fluid decreased in a time-dependent manner. Consequently, we suggest that the brain is the target organ of semi-SWCNTs brought into the lung, and conductance as well as length may be critical factors affecting the intensity and duration of the inflammatory response following SWCNT exposure.
Department of Molecular Science and Technology, Ajou University, Suwon, Korea.
Eun-Jung
EJ
Park
Jinkyu
J
Roh
Soo Nam
SN
Kim
Min-Sung
MS
Kang
Byoung-Seok
BS
Lee
Younghun
Y
Kim
Sangdun
S
Choi
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D055598:Chemical Phenomena; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005786:Gene Expression Regulation / Q000187:drug effects; D006403:Hematologic Tests; D006632:Histamine / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000090204:Mesothelin; D051379:Mice; D008813:Mice, Inbred ICR; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D023382:Toxicity Tests, Acute / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016207:Cytokines; C000715528:Msln protein, mouse; D037742:Nanotubes, Carbon; D016212:Transforming Growth Factor beta; D006632:Histamine; D000090204:Mesothelin