The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats

Rittinghausen, Susanne; Hackbarth, Anja; Creutzenberg, Otto; Ernst, Heinrich; Heinrich, Uwe; Leonhardt, A.; Schaudien, Dirk

doi:10.1186/s12989-014-0059-z

Cited by 157 publications

(137 citation statements)

References 55 publications

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“…It has been hypothesized that larger MWCNT, with a high length/diameter-aspect ratio, may resemble asbestos and be more carcinogenic and fibrogenic (Donaldson et al, 2010;Grosse et al, 2014). For example, intraperitoneal instillation of MWCNT of different lengths resulted in length-dependent infiltration of inflammatory cells in the peritoneal cavity of mice (Poland et al, 2008;Yamashita et al, 2010;Rittinghausen et al, 2014). Elevated inflammation, protein concentration, and fibrotic lesions along the parietal pleura and in the mesothelial layer were observed in mice exposed to long MWCNT via direct injection into the pleural cavity compared to mice exposed to short MWCNT.…”

Section: Introductionmentioning

confidence: 99%

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

Poulsen

Saber

Williams

et al. 2015

Toxicology and Applied Pharmacology

159

196

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Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of a small, curled (CNT(Small), 0.8 ± 0.1 μm in length) or large, thick MWCNT (CNT(Large), 4 ± 0.4 μm in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer-Emmett-Teller surface area analysis. Lung tissues were harvested 24h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bronchoalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNT(Small) or CNT(Large) were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNT(Large) elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNT(Small). The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNT(Large), which may eventually lead to the different responses observed at day 28.

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Section: Introductionmentioning

confidence: 99%

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

Poulsen

Saber

Williams

et al. 2015

Toxicology and Applied Pharmacology

159

196

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“…60 The nanometer scale and needle shape of CNTs recall that of crocidolite asbestos fibers, 54 and CNT administration has been associated with inflammation, fibrosis, and mesothelioma. 19,54,[61][62][63][64][65][66] Interestingly, previous studies documented the formation of granuloma and fibrosis upon pulmonary CNT exposure. 12,14,21,24,25 We did not observe Figure 5 Association between amyloid fibril deposits and macrophage recruitment.…”

Section: Discussionmentioning

confidence: 99%

“…CNT toxicity has been reported in rodent models by different routes of administration, such as intratracheal instillation, 8,[10][11][12][13] inhalation, 14 or intravenous, 15,16 subcutaneous 17 and intraperitoneal injection. 18,19 However, exposure to CNTs is likely to occur simultaneously by multiple routes of entry, as CNTs for their characteristics are able to diffuse in various environmental matrices. 20 For these reasons, we investigated whether and how these NPs are able to enter into the organism and interact with biological systems following external exposure and trigger possible pathological processes resulting from long-term exposure to MWCNTs.…”

Section: Introductionmentioning

confidence: 99%

Environmental impact of multi-wall carbon nanotubes in a novel model of exposure: systemic distribution, macrophage accumulation, and amyloid deposition

Albini¹,

Pagani²,

Pulze³

et al. 2015

IJN

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Carbon nanotubes (CNTs) have been extensively investigated and employed for industrial use because of their peculiar physical properties, which make them ideal for many industrial applications. However, rapid growth of CNT employment raises concerns about the potential risks and toxicities for public health, environment, and workers associated with the manufacture and use of these new materials. Here we investigate the main routes of entry following environmental exposure to multi-wall CNTs (MWCNTs; currently the most widely used in industry). We developed a novel murine model that could represent a surrogate of a workplace exposure to MWCNTs. We traced the localization of MWCNTs and their possible role in inducing an innate immune response, inflammation, macrophage recruitment, and inflammatory conditions. Following environmental exposure of CD1 mice, we observed that MWCNTs rapidly enter and disseminate in the organism, initially accumulating in lungs and brain and later reaching the liver and kidney via the bloodstream. Since recent experimental studies show that CNTs are associated with the aggregation process of proteins associated with neurodegenerative diseases, we investigated whether MWCNTs are able to induce amyloid fibril production and accumulation. Amyloid deposits in spatial association with macrophages and MWCNT aggregates were found in the brain, liver, lungs, and kidneys of exposed animals. Our data suggest that accumulation of MWCNTs in different organs is associated with inflammation and amyloid accumulation. In the brain, where we observed rapid accumulation and amyloid fibril deposition, exposure to MWCNTs might enhance progression of neurodegenerative and other amyloid-related diseases. Our data highlight the conclusion that, in a novel rodent model of exposure, MWCNTs may induce macrophage recruitment, activation, and amyloid deposition, causing potential damage to several organs.

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“…Zudem tritt eine zunehmende Verdickung der Alveolarsepten und Lä sionen entlang der parietalen Pleura auf. Nach i. p.Applikation bei der Ratte wird berichtet, dass verschiedene geradlinige CNT auch im Vergleich zu Krokydolith eine starke Mesotheliominduzierende Wirkung zeigen (Rittinghausen et al 2014 …”

Section: Wechselwirkungen Mit Endogenen Biomolekülen Und Nichtphagozyunclassified

Faserstäube, anorganisch [MAK Value Documentation in German language, 2018]

Hartwig

Arand²

2018

The MAK‐Collection for Occupational Health and Safety

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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has reevaluated the general aspects of the toxicity of inorganic fibrous dusts. As a first step a documentation on the effects caused by inhalation of inorganic fibrous dusts and the mode of action for their toxicity was set up. For the elucidation of the mechanism of the toxicity and carcinogenicity of fibers, data derived from studies with asbestos fibers were also considered, in order to obtain some knowledge with regard to the biological effects of the other inorganic fibrous dusts. The formation of tumors in the lungs and on serous membranes is mainly the result of inflammatory processes. Chronic inflammation and cell proliferation are caused by the impairment of fiber clearance, whereby inflammation‐promoting cytokines, growth factors, reactive oxygen (ROS) and nitrogen species (RNS) and chlorine radicals are released from the macrophages, inflammatory cells, alveolar cells and mesothelial cells. The generation of these radicals leads to genotoxic effects. In addition intracellular formation of ROS and RNS can be caused by the fibers themselves, as a result of their own surface reactivity. Fibers can stimulate cell receptors and inflammasomes. Each fiber dust group will be evaluated individually and, depending on the data available, may be classified in one of the categories for carcinogens. The Commission has already begun this procedure.

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The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats

Cited by 157 publications

References 55 publications

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

Environmental impact of multi-wall carbon nanotubes in a novel model of exposure: systemic distribution, macrophage accumulation, and amyloid deposition

Faserstäube, anorganisch [MAK Value Documentation in German language, 2018]

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