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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

Total protein content and MIP-1α in BALFs following exposure of rats to CNT-1, CNT-2, or vehicle controls at the indicated time points. Total protein content (A) and the levels of MIP-1α (B) in the BALF following exposure of rats to CNT-1, CNT-2, or vehicle controls at each time point. Values are represented as the mean ± SD. The asterisk indicates a statistically significant difference compared to the vehicle control group (multiple permutation-based Welch test, *p < 0.05, **p < 0.01).
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Figure 0002: Total protein content and MIP-1α in BALFs following exposure of rats to CNT-1, CNT-2, or vehicle controls at the indicated time points. Total protein content (A) and the levels of MIP-1α (B) in the BALF following exposure of rats to CNT-1, CNT-2, or vehicle controls at each time point. Values are represented as the mean ± SD. The asterisk indicates a statistically significant difference compared to the vehicle control group (multiple permutation-based Welch test, *p < 0.05, **p < 0.01).

Mentions: Lungs of anesthetized rats were excised and subjected to BALF analysis at 1, 3, 7, 30, and 90 d post-instillation. Total protein levels in the group exposed to a high dose of CNT-1 were significantly increased at 1 d post-instillation (p < 0.05) and further increased over time. In contrast, the high levels of total protein observed at 1 d post-instillation (p < 0.01) decreased over time in the group exposed to a high dose of CNT-2 (Figure 2A). MIP-1α levels were elevated during the observation period in groups exposed to a high dose of CNT-1 or CNT-2 (Figure 2B). Notably, significantly high MIP-1α levels in the group exposed to a high dose of CNT-1 were observed at 30 and 90 d post-instillation (p < 0.01).Figure 2.


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)

Total protein content and MIP-1α in BALFs following exposure of rats to CNT-1, CNT-2, or vehicle controls at the indicated time points. Total protein content (A) and the levels of MIP-1α (B) in the BALF following exposure of rats to CNT-1, CNT-2, or vehicle controls at each time point. Values are represented as the mean ± SD. The asterisk indicates a statistically significant difference compared to the vehicle control group (multiple permutation-based Welch test, *p < 0.05, **p < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 0002: Total protein content and MIP-1α in BALFs following exposure of rats to CNT-1, CNT-2, or vehicle controls at the indicated time points. Total protein content (A) and the levels of MIP-1α (B) in the BALF following exposure of rats to CNT-1, CNT-2, or vehicle controls at each time point. Values are represented as the mean ± SD. The asterisk indicates a statistically significant difference compared to the vehicle control group (multiple permutation-based Welch test, *p < 0.05, **p < 0.01).
Mentions: Lungs of anesthetized rats were excised and subjected to BALF analysis at 1, 3, 7, 30, and 90 d post-instillation. Total protein levels in the group exposed to a high dose of CNT-1 were significantly increased at 1 d post-instillation (p < 0.05) and further increased over time. In contrast, the high levels of total protein observed at 1 d post-instillation (p < 0.01) decreased over time in the group exposed to a high dose of CNT-2 (Figure 2A). MIP-1α levels were elevated during the observation period in groups exposed to a high dose of CNT-1 or CNT-2 (Figure 2B). Notably, significantly high MIP-1α levels in the group exposed to a high dose of CNT-1 were observed at 30 and 90 d post-instillation (p < 0.01).Figure 2.

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