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Size effects of single-walled carbon nanotubes on in vivo and in vitro pulmonary toxicity.

Fujita K, Fukuda M, Endoh S, Maru J, Kato H, Nakamura A, Shinohara N, Uchino K, Honda K - Inhal Toxicol (2015)

Bottom Line: 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.We conclude that the pulmonary toxicity of SWCNTs is closely associated with the size of the bundles.

View Article: PubMed Central - PubMed

Affiliation: Research Institute of Science for Safety and Sustainability (RISS), National Institute of Advanced Industrial Science and Technology (AIST) , Tsukuba, Ibaraki , Japan .

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.

No MeSH data available.


Related in: MedlinePlus

TEM images of mediastinal lymph nodes from rats exposed to CNT-1 or CNT-2 at a high dose at 90 d post-instillation. The mediastinal lymph nodes in the rats were fixed using 2.5% (v/v) glutaraldehyde for 2 h at 4 °C and 1% osmium oxide solution for 2 h at 4 °C, dehydrated in ethanol, and embedded in a commercially available epoxy resin. Samples were transferred to fresh resin in capsules and polymerized at 60 °C for 48 h. The TEM system was used to observe morphologic changes in the mediastinal lymph nodes of the rats.
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Figure 0005: TEM images of mediastinal lymph nodes from rats exposed to CNT-1 or CNT-2 at a high dose at 90 d post-instillation. The mediastinal lymph nodes in the rats were fixed using 2.5% (v/v) glutaraldehyde for 2 h at 4 °C and 1% osmium oxide solution for 2 h at 4 °C, dehydrated in ethanol, and embedded in a commercially available epoxy resin. Samples were transferred to fresh resin in capsules and polymerized at 60 °C for 48 h. The TEM system was used to observe morphologic changes in the mediastinal lymph nodes of the rats.

Mentions: TEM analysis showed that SWCNT bundles were present in mediastinal lymph nodes in the high-dose CNT-1 and CNT-2 groups at 90 d post-instillation (Figure 5). Some SWCNT bundles similar to those shown in Figure 1 were observed. No fiber tangle formation was identified.Figure 5.


Size effects of single-walled carbon nanotubes on in vivo and in vitro pulmonary toxicity.

Fujita K, Fukuda M, Endoh S, Maru J, Kato H, Nakamura A, Shinohara N, Uchino K, Honda K - Inhal Toxicol (2015)

TEM images of mediastinal lymph nodes from rats exposed to CNT-1 or CNT-2 at a high dose at 90 d post-instillation. The mediastinal lymph nodes in the rats were fixed using 2.5% (v/v) glutaraldehyde for 2 h at 4 °C and 1% osmium oxide solution for 2 h at 4 °C, dehydrated in ethanol, and embedded in a commercially available epoxy resin. Samples were transferred to fresh resin in capsules and polymerized at 60 °C for 48 h. The TEM system was used to observe morphologic changes in the mediastinal lymph nodes of the rats.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487552&req=5

Figure 0005: TEM images of mediastinal lymph nodes from rats exposed to CNT-1 or CNT-2 at a high dose at 90 d post-instillation. The mediastinal lymph nodes in the rats were fixed using 2.5% (v/v) glutaraldehyde for 2 h at 4 °C and 1% osmium oxide solution for 2 h at 4 °C, dehydrated in ethanol, and embedded in a commercially available epoxy resin. Samples were transferred to fresh resin in capsules and polymerized at 60 °C for 48 h. The TEM system was used to observe morphologic changes in the mediastinal lymph nodes of the rats.
Mentions: TEM analysis showed that SWCNT bundles were present in mediastinal lymph nodes in the high-dose CNT-1 and CNT-2 groups at 90 d post-instillation (Figure 5). Some SWCNT bundles similar to those shown in Figure 1 were observed. No fiber tangle formation was identified.Figure 5.

Bottom Line: 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.We conclude that the pulmonary toxicity of SWCNTs is closely associated with the size of the bundles.

View Article: PubMed Central - PubMed

Affiliation: Research Institute of Science for Safety and Sustainability (RISS), National Institute of Advanced Industrial Science and Technology (AIST) , Tsukuba, Ibaraki , Japan .

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.

No MeSH data available.


Related in: MedlinePlus