Evaluation of genotoxicity of multi-walled carbon nanotubes in a battery of in vitro and in vivo assays

Ema, Makoto; Imamura, Tadashi; Suzuki, Hiroshi; Kobayashi, Norihiro; Naya, Masato; Nakanishi, Junko

doi:10.1016/j.yrtph.2012.03.014

Cited by 58 publications

(38 citation statements)

References 28 publications

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“…Thus, the presence of high levels of cytochrome P450 found in descendants of the HB cross is not important in inducing mutant spots in Drosophila, when larvae were exposed to carbon nanotubes. Our results were supported by Ema et al (2012) that found neither type exerted mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, and TA1537, or in Escherichia coli WP2uvrA, in the absence or presence of metabolic activation.…”

Section: Discussionsupporting

confidence: 85%

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Lack of mutagenic effect by multi-walled functionalized carbon nanotubes in the somatic cells of Drosophila melanogaster

Machado

Lopes

Saturnino

et al. 2013

Food and Chemical Toxicology

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Carbon nanotubes (CNTs) are formed by rolling up a single graphite sheet into a tube. Among the different types of CNTs, the multi-walled carbon nanotubes (MWCNTs) comprise a set of concentric nanotubes with perfect structures. Several uses for MWCNTs have been suggested to be included in biological applications such as manufacturing of biosensors, carriers of drugs. However, before these materials can be put on the market, it is necessary to know their genotoxic effects. Thus, this study aims to evaluate the mutagenicity of multi-walled carbon nanotubes (MWCNTs) functionalized in somatic cells of Drosophila melanogaster, using the somatic mutation and recombination test (SMART). This assay detects the loss of heterozygosity of marker genes expressed phenotypically on the wings of the fly. Larvae of three days were used, resulting from ST cross, with basal levels of the cytochrome P450 and larvae of high metabolic bioactivity capacity (HB cross). They were treated with different concentrations of MWCNTs functionalized. The MH descendants, analyzed in both ST and HB crosses, had no significant effects on the frequency of mutant. Based on the results and on the experimental conditions mentioned in this study, it was concluded that MWCNTs were not mutagenic in D. melanogaster.

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Section: Discussionsupporting

confidence: 85%

“…On the other hand, Petersen et al (2013) suggest that SWCNTs can help protect DNA molecules from oxidative damage. According to Ema et al (2012) MWCNTs had no genotoxic activity in the in vivo micronucleus test, by the lack of micronuclei or chromosomal damage in mouse bone marrow erythrocytes at the maximum dosing limit.…”

Section: Introductionmentioning

confidence: 99%

Lack of mutagenic effect by multi-walled functionalized carbon nanotubes in the somatic cells of Drosophila melanogaster

Machado

Lopes

Saturnino

et al. 2013

Food and Chemical Toxicology

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“…We previously reported that SWCNTs were not genotoxic under the conditions tested with an in vitro bacterial reverse-mutation assay, a chromosomal-aberration assay, or an in vivo bone marrow-micronucleus test (Ema et al, 2013b;Naya et al, 2011). 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).…”

Section: Test Substance Findingsmentioning

confidence: 99%

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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“…There are several reports on the in vivo genotoxicity of MWCNTs, but they provide conflicting data [12–15]. In vivo comet assay revealed that a single intratracheal or pharyngeal instillation of MWCNTs to mice both induced DNA damage in the lungs in a dose-dependent manner [13, 15].…”

Section: Introductionmentioning

confidence: 99%

Absence of in vivo mutagenicity of multi-walled carbon nanotubes in single intratracheal instillation study using F344 gpt delta rats

et al. 2017

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IntroductionIt is known that fibrous particles of micrometer length, such as carbon nanotubes, which have same dimensions as asbestos, are carcinogenic. Carcinogenicity of nanomaterials is strongly related to inflammatory reactions; however, the genotoxicity mechanism(s) is unclear. Indeed, inconsistent results on genotoxicity of multi-walled carbon nanotubes (MWCNTs) have been shown in several reports. Therefore, we analyzed the in vivo genotoxicity induced by an intratracheal instillation of straight MWCNTs in rats using a different test system—the Pig-a gene mutation assay—that can reflect the genotoxicity occurring in the bone marrow. Since lungs were directly exposed to MWCNTs upon intratracheal instillation, we also performed the gpt assay using the lungs.FindingsWe detected no significant differences in Pig-a mutant frequencies (MFs) between the MWCNT-treated and control rats. Additionally, we detected no significant differences in gpt MFs in the lung between the MWCNT-treated and control rats.ConclusionsOur findings indicated that a single intratracheal instillation of MWCNTs was non-mutagenic to both the bone marrow and lung of rats.

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Evaluation of genotoxicity of multi-walled carbon nanotubes in a battery of in vitro and in vivo assays

Cited by 58 publications

References 28 publications

Lack of mutagenic effect by multi-walled functionalized carbon nanotubes in the somatic cells of Drosophila melanogaster

Lack of mutagenic effect by multi-walled functionalized carbon nanotubes in the somatic cells of Drosophila melanogaster

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

Absence of in vivo mutagenicity of multi-walled carbon nanotubes in single intratracheal instillation study using F344 gpt delta rats

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