Genotoxicity of nanomaterials: DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibres in human bronchial epithelial cells in vitro

Lindberg, Hanna; Falck, Ghita C.-M.; Suhonen, Satu; Vippola, Minnamari; Vanhala, Esa; Catalán, Julia; Savolainen, Kai; Norppa, Hannu

doi:10.1016/j.toxlet.2008.11.019

Cited by 268 publications

(141 citation statements)

References 34 publications

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“…59 The increase in oxidative stress could modify proteins, lipids and nucleic acids, which, in the long-term stimulate the antioxidant defense response or even induce cellular death. 53,60 Some studies suggest that cytotoxicity induced by CNTs may be the result of ROS generated from the iron catalyzer, probably as a result of the Fenton reaction; 61 however, in our study, we did not find changes in the production of ROS (Figures 10 and 11). Also, studies in leukemia cells did not find significant differences in the ROS levels between treated and untreated cells, 62 suggesting To determine whether MWCNTs treatment induces toxic effects in healthy rats, we injected 50 µg/10 µL of MWCNTs/ PBS.…”

Section: Discussioncontrasting

confidence: 63%

“…Lindberg et al have suggested that MWCNTs efficiently interact with biomolecules by stimulating the formation of non-covalent conjugates (protein-MWCNT); such conjugates may be transported inside mammalian cells via endocytosis. 53 Once these conjugates have been freed by the lysosomes, they are internalized into cytoplasm interfering with biological functions, which becomes evident by the induction of apoptosis and the expression of the BCL-2 protein family; in turn, when Bcl-2 is expressed, it causes the release of cytochrome C from the mitochondria to the cytosol. 54,55 To evaluate how MWCNTs could induce cellular damage, we analyzed cell cycle progression.…”

Section: Discussionmentioning

confidence: 99%

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Cytotoxicity induced by carbon nanotubes in experimental malignant glioma

Romano-Feinholz¹,

Salazar-Ramiro

Muñoz‐Sandoval³

et al. 2017

IJN

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Despite multiple advances in the diagnosis of brain tumors, there is no effective treatment for glioblastoma. Multiwalled carbon nanotubes (MWCNTs), which were previously used as a diagnostic and drug delivery tool, have now been explored as a possible therapy against neoplasms. However, although the toxicity profile of nanotubes is dependent on the physicochemical characteristics of specific particles, there are no studies exploring how the effectivity of the carbon nanotubes (CNTs) is affected by different methods of production. In this study, we characterize the structure and biocompatibility of four different types of MWCNTs in rat astrocytes and in RG2 glioma cells as well as the induction of cell lysis and possible additive effect of the combination of MWCNTs with temozolomide. We used undoped MWCNTs (labeled simply as MWCNTs) and nitrogen-doped MWCNTs (labeled as N-MWCNTs). The average diameter of both pristine MWCNTs and pristine N-MWCNTs was ~22 and ~35 nm, respectively. In vitro and in vivo results suggested that these CNTs can be used as adjuvant therapy along with the standard treatment to increase the survival of rats implanted with malignant glioma.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Cytotoxicity induced by carbon nanotubes in experimental malignant glioma

Romano-Feinholz¹,

Salazar-Ramiro

Muñoz‐Sandoval³

et al. 2017

IJN

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“…Destabilization of the DNA structure can induce chromosome breakage. In vitro investigations have shown SWCNT-induced DNA damage in established cancer cell lines, immortalized bronchial epithelial cells as well as primary mouse embryo fibroblasts and human mesothelial cells [18][19][20]. Micronuclei have been observed in significant numbers following in vitro treatment with SWCNT or MWCNT indicating disruption of the mitotic spindle apparatus [19,21].…”

Section: Introductionmentioning

confidence: 99%

Single-walled carbon nanotube-induced mitotic disruption

Sargent

Hubbs

Young

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

148

123

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Carbon nanotubes were among the earliest products of nanotechnology and have many potential applications in medicine, electronics, and manufacturing. The low density, small size, and biological persistence of carbon nanotubes create challenges for exposure control and monitoring and make respiratory exposures to workers likely. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to 24, 48 and 96 μg/cm 2 single-walled carbon nanotubes (SWCNT). To investigate mitotic spindle aberrations at concentrations anticipated in exposed workers, primary and immortalized human airway epithelial cells were exposed to SWCNT for 24-72 h at doses equivalent to 20 weeks of exposure at the Permissible Exposure Limit for particulates not otherwise regulated. We have now demonstrated fragmented centrosomes, disrupted mitotic spindles and aneuploid chromosome number at those doses. The data further demonstrated multipolar mitotic spindles comprised 95% of the disrupted mitoses. The increased multipolar mitotic spindles were associated with an increased number of cells in the G2 phase of mitosis, indicating a mitotic checkpoint response. Nanotubes were observed in association with mitotic spindle microtubules, the centrosomes and condensed chromatin in cells exposed to 0.024, 0.24, 2.4 and 24 μg/cm 2 SWCNT. Three- Conflict of interest statementThe authors declare that there are no conflicts of interest. Appendix A. Supplementary dataSupplementary data associated with this article can be found, in the online version, at doi:10.1016/j.mrgentox.2011.11.017. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript dimensional reconstructions showed carbon nanotubes within the centrosome structure. The lower doses did not cause cytotoxicity or reduction in colony formation after 24 h; however, after three days, significant cytotoxicity was observed in the SWCNT-exposed cells. Colony formation assays showed an increased proliferation seven days after exposure. Our results show significant disruption of the mitotic spindle by SWCNT at occupationally relevant doses. The increased proliferation that was observed in carbon nanotube-exposed cells indicates a greater potential to pass the genetic damage to daughter cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is an early event in the progression of many cancers, suggesting that it may play a role in both tumorigenesis and tumor progression. These results suggest caution should be used in the handling and processing of carbon nanotubes.

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“…Whilst there is good reason to be concerned about the potential similarities to asbestos fibres, there is evidence to suggest that industrially produced MWCNTs in high doses do not result in cell death in lung epithelial (tissue) in the way that asbestos fibres do. Additionally, long term exposure to pristine MWCNTs at low concentrations did not cause any major adverse effects (Lindberg et al, 2009).…”

Section: Toxicity Of Carbon Nanotubesmentioning

confidence: 90%

Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

Kushwaha¹,

Ghoshal²,

Kumar³

et al. 2013

Braz. J. Pharm. Sci.

115

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Carbon nanotubes (CNTs) were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field.Uniterms: Carbon nanotubes/properties. Carbon nanotubes/use/drugs delivery. Single-Walled Carbon Nanotube. Multiwalled Carbon Nanotube. Anticancer drugs/delivery. Cancer/therapy. Drugs/delivery.Os nanotubos de carbono foram descobertos em 1991 e suas propriedades físico-químicas únicas demonstradas, despertando interesse em sua aplicação em vários campos, incluindo a entrega liberação de fármacos. As propriedades únicas dos nanotubos de carbono, tais como a facilidade de captação pela célula, carga alta de fármaco, ablação térmica, entre outras, tornaram-nos úteis para terapia de câncer, uma das doenças mais difíceis dos tempos modernos, pois sua terapia envolve a distinção entre as células normais saudáveis e as afetadas pela doença. Os nanotubos de carbono têm um papel importante nessa área porque fenômenos como EPR permitem que estes possam distinguir as células normais das afetadas, que é o Santo Graal na terapia do câncer. Trabalho considerável tem sido feito ao longo das duas últimas década com nanotubos de carbono, como sistemas de liberação de fármacos. No entanto, preocupações sobre algumas questões, como biocompatibilidade e toxicidade, surgiram ao longo do tempo, demandando extensas pesquisa nesse campo. Unitermos: Nanotubos de carbono/propriedades. Nanotubos de carbono/uso/liberação de fármacos. Nanotubo de carbono de parede única. Nanotubo de parede múltipla. Fármacos anticancer/liberação. Cancer/tratamento. Fármacos/liberação.

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Genotoxicity of nanomaterials: DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibres in human bronchial epithelial cells in vitro

Cited by 268 publications

References 34 publications

Cytotoxicity induced by carbon nanotubes in experimental malignant glioma

Cytotoxicity induced by carbon nanotubes in experimental malignant glioma

Single-walled carbon nanotube-induced mitotic disruption

Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

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