In vivo genotoxicity study of single-wall carbon nanotubes using comet assay following intratracheal instillation in rats

Naya, Masato; Kobayashi, Norihiro; Endoh, Shigehisa; Maru, Junko; Honda, Kazumasa; Ema, Makoto; Tanaka, Jin; Fukumuro, Masahito; Hasegawa, Kazushige; Nakajima, Masahiro; Hayashi, Makoto; Nakanishi, Junko

doi:10.1016/j.yrtph.2012.05.020

Cited by 23 publications

(17 citation statements)

References 28 publications

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“…In the present study, S-SWCNTs induced a more severe pulmonary toxicity despite having a slightly lower iron content than the L-SWCNTs did. In our previous studies, the pulmonary toxicity of short-tube N-SWCNTs, which contained a high amount iron as an impurity (13700 ppm), was studied in rats (Naya et al, 2012;Fujita et al, 2015b). We observed that the pulmonary inflammation induced by N-SWCNTs in the previous studies is not markedly different from that induced by S-SWCNTs in the present study.…”

Section: Discussioncontrasting

confidence: 46%

“…The N-SWCNTs, whether singly instilled (at 0.2 or 1.0 mg/kg) or repeatedly instilled (once a week for 5 weeks at 0.04 or 0.2 mg/kg), induced acute pulmonary inflammation. However, no DNA damage in lung tissues was observed in comet assays at any of the doses studied (Naya et al, 2012). In another study, following a single intratracheal instillation of N-SWCNTs at 0.66 or 1.32 mg/kg, persistent (6 months) pulmonary inflammation was observed at both doses.…”

Section: Discussionmentioning

confidence: 86%

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Length effects of single-walled carbon nanotubes on pulmonary toxicity after intratracheal instillation in rats

Ema

Takehara²,

Naya

et al. 2017

J. Toxicol. Sci.

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-We aimed to evaluate the effects of the length of single-walled carbon nanotubes (SWCNTs) on pulmonary toxicity in rats. Each rat received a single intratracheal instillation of short (S-) (average length of 0.40 μm) or long (L-) (average length of 2.77 μm) SWCNTs at a dose of 1 mg/kg and was observed for the next 6 months. Neither S-nor L-SWCNTs affected clinical signs, body weight, or autopsy findings. An increase in lung weight was observed after instillation of S-or L-SWCNTs; however, lung weights were slightly higher in the rats that were administered the S-SWCNTs. Distinct differences in bronchoalveolar lavage fluid (BALF) composition were observed between the S-and L-SWCNTtreated rats as early as 7 days after the intratracheal instillations of the SWCNTs. The S-SWCNTs caused persistent lung injury and inflammation during the 6-month observational period. However, the L-SWCNTs induced minimal lung injury and inflammation. Although the S-and L-SWCNTs changed BALF parameters and histopathological features of the lung, the magnitudes of the changes observed after the S-SWCNT treatment were greater than the respective changes observed after the L-SWCNT treatment. These findings indicate that the severity of the pulmonary toxicity caused after intratracheal instillation of SWCNT depends on the length of the SWCNTs. It appears that shorter SWCNTs induce greater pulmonary toxicity than longer SWCNTs do.

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Section: Discussioncontrasting

confidence: 46%

Section: Discussionmentioning

confidence: 86%

Length effects of single-walled carbon nanotubes on pulmonary toxicity after intratracheal instillation in rats

Ema

Takehara²,

Naya

et al. 2017

J. Toxicol. Sci.

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“…Furthermore, intratracheal instillation of SWCNTs did not induce DNA damage in a comet assay using lung tissues of rats singly instilled at 0.3 or 1.0 mg/kg or repeatedly (once a week for 5 weeks) at 0.04 or 0.2mg/(kgÁd) (Naya et al, 2012). These negative results were observed even at doses that elicited pulmonary inflammation.…”

Section: Test Substance Findingsmentioning

confidence: 92%

A 104-week pulmonary toxicity assessment of long and short single-wall carbon nanotubes after a single intratracheal instillation in rats

Honda

Naya

Takehara

et al. 2017

Inhalation Toxicology

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We compared long-term pulmonary toxicities after a single intratracheal instillation of two types of dispersed single-wall carbon nanotubes (SWCNTs), namely, those with relatively long or short linear shapes with average lengths of 8.6 and 0.55 mm, respectively. Both types of SWCNTs were instilled intratracheally in male F344 rats at 0.2 or 1.0 mg/kg (long SWCNTs) or 1.0 mg/kg (short SWCNTs). Pulmonary responses were characterized at 26, 52 and 104 weeks after a single instillation. Inflammatory changes, test substance deposition, test substance engulfment by macrophages, and alveolar wall fibrosis were observed in the lungs of almost all test rats at 52 and 104 weeks after short nanotube instillation. The incidences of these changes were much lower in the long nanotube-treated groups. In almost all rats of the long nanotube-treated groups, fibrosis and epithelium loss in the terminal bronchiole with test substance deposition were observed. These bronchiolar changes were not observed after administering short nanotubes. Both bronchiolo-alveolar adenoma and carcinoma were found in the negative-control group, the high-dose long-nanotube group, and the short-nanotube group at 104 weeks post-instillation, although the incidences were not statistically different. The genotoxicity of the SWCNTs was also evaluated by performing in vivo comet assays with lung cells obtained 26 weeks post-instillation. No significant changes in the percent tail deoxyribonucleic acid were found in any group. These findings suggested that most long SWCNTs were deposited at the terminal bronchioles and that a considerable amount of short SWCNTs reached the alveolus, resulting in chronic inflammatory responses, but no genotoxicity in the lungs. ARTICLE HISTORY

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“…However, other researches showed no genotoxic effects of TiO 2 NPs in vivo when intravenously administrated [16,35,36] or inhaled [14,15] for short exposure times. These disparities may be due to differences in the test conditions, such as exposure time, concentrations, animal model, the dispersal of the particles, and the physicochemical characteristics of TiO 2 used by the investigators.…”

Section: Discussionmentioning

confidence: 95%

“…Additionally, if NPs are able to accumulate within a cell but not necessarily gain access to the nucleus, they may still come into direct contact with DNA during mitosis, when the nuclear membrane breaks down, providing an opportunity for DNA aberrations to arise [5]. The genotoxicity of TiO 2 NPs has been intensively studied in vitro [6][7][8][9][10][11] and in vivo [12][13][14][15][16] , but few studies have evaluated the genotoxic potential of TiO 2 NPs exposed by oral administration [17][18][19]. Overall, these studies evaluated short-term and/or high-dose oral exposure of TiO 2 NPs to animals.…”

Section: Introductionmentioning

confidence: 99%

Anemia and genotoxicity induced by sub-chronic intragastric treatment of rats with titanium dioxide nanoparticles

Grissa

Elghoul

Ezzi

et al. 2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

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In vivo genotoxicity study of single-wall carbon nanotubes using comet assay following intratracheal instillation in rats

Cited by 23 publications

References 28 publications

Length effects of single-walled carbon nanotubes on pulmonary toxicity after intratracheal instillation in rats

Length effects of single-walled carbon nanotubes on pulmonary toxicity after intratracheal instillation in rats

A 104-week pulmonary toxicity assessment of long and short single-wall carbon nanotubes after a single intratracheal instillation in rats

Anemia and genotoxicity induced by sub-chronic intragastric treatment of rats with titanium dioxide nanoparticles

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