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Intratracheal instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression.

Fujita K, Fukuda M, Fukui H, Horie M, Endoh S, Uchida K, Shichiri M, Morimoto Y, Ogami A, Iwahashi H - Nanotoxicology (2014)

Bottom Line: In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12 and Rnase9 were significantly upregulated until 754 days post-instillation.We propose that these persistently upregulated genes in the chronic-phase response following the acute-phase response act as potential biomarkers in lung tissue after SWCNT instillation.This study provides further insight into the time-dependent changes in genomic expression associated with the pulmonary toxicity of SWCNTs.

View Article: PubMed Central - PubMed

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

ABSTRACT
The use of carbon nanotubes in the industry has grown; however, little is known about their toxicological mechanism of action. Single-wall carbon nanotube (SWCNT) suspensions were administered by single intratracheal instillation in rats. Persistence of alveolar macrophage-containing granuloma was observed around the sites of SWCNT aggregation at 90 days post-instillation in 0.2-mg- or 0.4-mg-injected doses per rat. Meanwhile, gene expression profiling revealed that a large number of genes involved in the inflammatory response were markedly upregulated until 90 days or 180 days post-instillation. Subsequently, gene expression patterns were dramatically altered at 365 days post-instillation, and the number of upregulated genes involved in the inflammatory response was reduced. These results suggested that alveolar macrophage-containing granuloma reflected a characteristic of the histopathological transition period from the acute-phase to the subchronic-phase of inflammation, as well as pulmonary acute phase response persistence up to 90 or 180 days after intratracheal instillation in this experimental setting. The expression levels of the genes Ctsk, Gcgr, Gpnmb, Lilrb4, Marco, Mreg, Mt3, Padi1, Slc26a4, Spp1, Tnfsf4 and Trem2 were persistently upregulated in a dose-dependent manner until 365 days post-instillation. In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12 and Rnase9 were significantly upregulated until 754 days post-instillation. We propose that these persistently upregulated genes in the chronic-phase response following the acute-phase response act as potential biomarkers in lung tissue after SWCNT instillation. This study provides further insight into the time-dependent changes in genomic expression associated with the pulmonary toxicity of SWCNTs.

No MeSH data available.


Related in: MedlinePlus

Body weight of rats after intratracheal instillation of SWCNTs: the vehicle control (0.1% Triton X-100 per rat; vehicle control) and the SWCNTs in the low-dose (0.2 mg SWCNTs per rat; L-SWCNT) or high-dose (0.4 mg SWCNTs per rat; H-SWCNT) groups. Values are mean ± SD. *p < 0.05, **p < 0.01 (vs. each vehicle control group).
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Figure 0001: Body weight of rats after intratracheal instillation of SWCNTs: the vehicle control (0.1% Triton X-100 per rat; vehicle control) and the SWCNTs in the low-dose (0.2 mg SWCNTs per rat; L-SWCNT) or high-dose (0.4 mg SWCNTs per rat; H-SWCNT) groups. Values are mean ± SD. *p < 0.05, **p < 0.01 (vs. each vehicle control group).

Mentions: Statistically significant differences in the body weights of experimental animals were observed between the H-SWCNT group and the vehicle control group at 3 days (p < 0.05), 180 days (p < 0.05) and 365 days (p < 0.01) post-instillation (Figure 1). By contrast, statistically significant differences in lung weight were not observed between any of the experimental groups and the vehicle control group (data not shown). No clinical signs, such as abnormal behavior and irregular respiration, were observed during the observation period in any of the groups. The total number of deaths observed was the following: one in the control vehicle group, two in the L-SWCNT group and three in the H-SWCNT group. In the control vehicle group, a rat that experienced a reduction in body weight was slaughtered at 704 days post-instillation. In the L-SWCNT group, a rat that experienced a reduction in body weight and a rat with swelling in the nasal region were slaughtered at 506 days and 704 days post-instillation, respectively. In the H-SWCNT group, three rats that experienced a reduction in body weight were slaughtered at 459, 569 and 587 days post-instillation, respectively.Figure 1.


Intratracheal instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression.

Fujita K, Fukuda M, Fukui H, Horie M, Endoh S, Uchida K, Shichiri M, Morimoto Y, Ogami A, Iwahashi H - Nanotoxicology (2014)

Body weight of rats after intratracheal instillation of SWCNTs: the vehicle control (0.1% Triton X-100 per rat; vehicle control) and the SWCNTs in the low-dose (0.2 mg SWCNTs per rat; L-SWCNT) or high-dose (0.4 mg SWCNTs per rat; H-SWCNT) groups. Values are mean ± SD. *p < 0.05, **p < 0.01 (vs. each vehicle control group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487535&req=5

Figure 0001: Body weight of rats after intratracheal instillation of SWCNTs: the vehicle control (0.1% Triton X-100 per rat; vehicle control) and the SWCNTs in the low-dose (0.2 mg SWCNTs per rat; L-SWCNT) or high-dose (0.4 mg SWCNTs per rat; H-SWCNT) groups. Values are mean ± SD. *p < 0.05, **p < 0.01 (vs. each vehicle control group).
Mentions: Statistically significant differences in the body weights of experimental animals were observed between the H-SWCNT group and the vehicle control group at 3 days (p < 0.05), 180 days (p < 0.05) and 365 days (p < 0.01) post-instillation (Figure 1). By contrast, statistically significant differences in lung weight were not observed between any of the experimental groups and the vehicle control group (data not shown). No clinical signs, such as abnormal behavior and irregular respiration, were observed during the observation period in any of the groups. The total number of deaths observed was the following: one in the control vehicle group, two in the L-SWCNT group and three in the H-SWCNT group. In the control vehicle group, a rat that experienced a reduction in body weight was slaughtered at 704 days post-instillation. In the L-SWCNT group, a rat that experienced a reduction in body weight and a rat with swelling in the nasal region were slaughtered at 506 days and 704 days post-instillation, respectively. In the H-SWCNT group, three rats that experienced a reduction in body weight were slaughtered at 459, 569 and 587 days post-instillation, respectively.Figure 1.

Bottom Line: In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12 and Rnase9 were significantly upregulated until 754 days post-instillation.We propose that these persistently upregulated genes in the chronic-phase response following the acute-phase response act as potential biomarkers in lung tissue after SWCNT instillation.This study provides further insight into the time-dependent changes in genomic expression associated with the pulmonary toxicity of SWCNTs.

View Article: PubMed Central - PubMed

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

ABSTRACT
The use of carbon nanotubes in the industry has grown; however, little is known about their toxicological mechanism of action. Single-wall carbon nanotube (SWCNT) suspensions were administered by single intratracheal instillation in rats. Persistence of alveolar macrophage-containing granuloma was observed around the sites of SWCNT aggregation at 90 days post-instillation in 0.2-mg- or 0.4-mg-injected doses per rat. Meanwhile, gene expression profiling revealed that a large number of genes involved in the inflammatory response were markedly upregulated until 90 days or 180 days post-instillation. Subsequently, gene expression patterns were dramatically altered at 365 days post-instillation, and the number of upregulated genes involved in the inflammatory response was reduced. These results suggested that alveolar macrophage-containing granuloma reflected a characteristic of the histopathological transition period from the acute-phase to the subchronic-phase of inflammation, as well as pulmonary acute phase response persistence up to 90 or 180 days after intratracheal instillation in this experimental setting. The expression levels of the genes Ctsk, Gcgr, Gpnmb, Lilrb4, Marco, Mreg, Mt3, Padi1, Slc26a4, Spp1, Tnfsf4 and Trem2 were persistently upregulated in a dose-dependent manner until 365 days post-instillation. In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12 and Rnase9 were significantly upregulated until 754 days post-instillation. We propose that these persistently upregulated genes in the chronic-phase response following the acute-phase response act as potential biomarkers in lung tissue after SWCNT instillation. This study provides further insight into the time-dependent changes in genomic expression associated with the pulmonary toxicity of SWCNTs.

No MeSH data available.


Related in: MedlinePlus