Biological Toxicity and Inflammatory Response of Semi-Single-Walled Carbon Nanotubes
et al. (2011) Biological Toxicity and Inflammatory Response of Semi-Single-Walled Carbon Nanotubes. PLoS
ONE 6(10): e25892. doi:10.1371/journal.pone.0025892
Biological Toxicity and Inflammatory Response of Semi- Single-Walled Carbon Nanotubes
Eun-Jung Park 0
Jinkyu Roh 0
Soo Nam Kim 0
Min-Sung Kang 0
Byoung-Seok Lee 0
Younghun Kim 0
Sangdun Choi 0
Vipul Bansal, RMIT University, Australia
0 1 Department of Molecular Science and Technology, Ajou University , Suwon , Korea , 2 Department of Chemical Engineering, Kwangwoon University , Seoul , Korea , 3 Inhalation Toxicology Center, Korea Institute of Toxicology , Jeongeup , Korea
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)-b, 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-b 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.
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Funding: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of
Education, Science and Technology (2010-0016256). This work was also partly supported by a grant from the Korea Food and Drug Administration
(10182KFDA992-2302) and the Priority Research Centers Program (NRF 2010-0028294). The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Because of advances in scientific research and technology,
nanomaterials, including carbon nanotubes (CNTs), are now used
in biomedical, cosmetic, aeronautics, electronics, and other
industries. Further, their effects on human health are also gaining
enormous attention from the public.
Single-walled carbon nanotubes (SWCNTs) have been included
in the priority list of OECD (Organization for Economic
Cooperation and Development) and have been introduced in many
new technologies for various industrial applications. Many
epidemiological and toxicological studies have reported on the
adverse health effects of SWCNTs [1,2,3,4]. According to these
reports, CNTs cause adverse health effects such as pulmonary
inflammation, granulomatous lesions, fibrosis, and mesothelioma
by inducing oxidative stress and free radical generation after
inflow of SWCNTs into the lung [2,5,6,7,8]. When experimental
animals were treated with SWCNTs, crocidolite asbestos, and
ultrafine carbon black of the same concentration, SWCNTs
caused the greatest histopathological changes, and lung tissue
proteins affected by SWCNT exposure largely represent cellular
processes affected by asbestos as well [9]. Nitric oxide (NO)
production increased and mitochondrial activity decreased after
an engineered human lung was exposed to SWCNTs [10], and
treatment with SWCNTs and ovalbumin (OVA) strongly
promoted an OVA-specific allergic response [11]. The results of
microarray analysis following intratracheal instillation of
SWCNTs suggest that an immunotoxicological mechanism may
explain the chronic pulmonary inflammation and granuloma
formation caused by SWCNTs in vivo [1]. Pharyngeal aspiration of
SWCNTs also elicited unusual pulmonary effects in mice,
combining a robust but acute inflammation with early onset yet
progressive fibrosis and granulomas [6]. In addition, a single
intrapharyngeal instillation of SWCNTs induced activation of
heme oxygenase-1 (HO-1) in HO-1 reporter transgenic mice and
aort (...truncated)