Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice

Shvedova, Anna A.; Kisin, Elena R.; Mercer, Robert R.; Murray, Ashley R.; Johnson, Victor J.; Potapovich, Alla I.; Tyurina, Yulia Y.; Gorelik, Olga; Arepalli, Sivaram; Schwegler‐Berry, Diane; Hubbs, Ann F.; Antonini, James M.; Evans, Douglas E.; Ku, Bon Ki; Ramsey, Dawn; Maynard, Andrew; Kagan, Valerian E.; Castranova, Vincent; Baron, Paul A.

doi:10.1152/ajplung.00084.2005

Cited by 1,193 publications

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“…It has been described that nanotubes exhibit various effects on biomolecules, such as stimulation as well as inhibition of the polymerase chain reaction. 49 Moreover, studies with living organisms indicate adverse effects for CNTs in mice and rats, 21,23,24 and a comparable cell agglomeration in vitro has been shown here ( Figure 2B). The lung granuloma as well as the accumulation of cells in culture in close proximity of larger CNT bundles suggest an attractive role of CNT surfaces without acute toxicity.…”

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confidence: 80%

Oops They Did It Again! Carbon Nanotubes Hoax Scientists in Viability Assays

2006

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New materials of emerging technological importance are single-walled carbon nanotubes (SWCNTs). Because SWCNTs will be used in commercial products in huge amounts, their effects on human health and the environment have been addressed in several studies. Inhalation studies in vivo and submerse applications in vitro have been described with diverging results. Why some indicate a strong cytotoxicity and some do not is what we report on here. Data from A549 cells incubated with carbon nanotubes fake a strong cytotoxic effect within the MTT assay after 24 h that reaches roughly 50%, whereas the same treatment with SWCNTs, but detection with WST-1, reveals no cytotoxicity. LDH, FACSassisted mitochondrial membrane potential determination, and Annexin-V/PI staining also reveal no cytotocicity. SWCNTs appear to interact with some tetrazolium salts such as MTT but not with others (such as WST-1, INT, XTT). This interference does not seem to affect the enzymatic reaction but lies rather in the insoluble nature of MTT−formazan. Our findings strongly suggest verifying cytotoxicity data with at least two or more independent test systems for this new class of materials (nanomaterials). Moreover, we intensely recommend standardizing nanotoxicological assays with regard to the material used: there is a clear need for reference materials. MTT−formazan crystals formed in the MTT reaction are lumped with nanotubes and offer a potential mechanism to guide bioremediation and clearance for SWCNTs from "contaminated" tissue. SWCNTs are good supporting materials for tissue growth, as attachment of focal adhesions and connections to the cytoskeleton suggest.

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confidence: 80%

Oops They Did It Again! Carbon Nanotubes Hoax Scientists in Viability Assays

2006

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“…1,11,12 For example, pharyngeal aspiration of purified SWCNTs (10-40 μg/ mouse) resulted in (1) a dose-dependent and rapid but transient inflammatory and injury response, (2) a rapid and persistent granulomatous response, and (3) alveolar interstitial fibrosis of rapid onset and progressive nature. 13 Short-term (4 days) inhalation exposure to SWCNTs induced a similar spectrum of pulmonary reactions. 14 On an equal mass lung burden basis, the fibrotic response following inhalation was 4-fold greater than after aspiration of SWCNTs.…”

Section: A Pulmonary Responsesmentioning

confidence: 98%

“…14 On an equal mass lung burden basis, the fibrotic response following inhalation was 4-fold greater than after aspiration of SWCNTs. 13,14 This was because SWCNTs were more dispersed in the dry aerosol (inhalation exposure) than in an aqueous suspension (pharyngeal aspiration). Aspiration of a well-dispersed suspension of SWCNTs resulted in a less severe granulomatous response and a 4-fold greater interstitial fibrotic response than a poorly dispersed SWCNT suspension.…”

Section: A Pulmonary Responsesmentioning

confidence: 99%

“…These inflammatory and fibrotic pulmonary responses to CNTs have also been associated with measurable alterations of pulmonary function, that is, an increase in expiratory time with SWCNTs and decreased compliance with increased resistance with aspiration of MWCNTs. 13,20 Evidence also indicates that SWCNT exposure also decreases the ability of the lung to resist infection. 21 Recent studies indicate that functionalization of MWCNTs with −COOH groups significantly decreases the inflammatory and fibrotic response after aspiration in a mouse model.…”

Section: A Pulmonary Responsesmentioning

confidence: 99%

“…Similarly, the inflammatory response to aspiration of raw (17.7% iron) vs purified (0.23% iron) SWCNTs was not significantly different. 13,14 …”

Section: A Contaminating Metalsmentioning

confidence: 99%

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Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

2012

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CONSPECTUSCarbon nanotubes (CNTs) are carbon atoms arranged in a crystalline graphene lattice with a tubular morphology. CNTs exhibit high tensile strength, possess unique electrical properties, are durable, and can be functionalized. These properties allow applications as structural materials, in electronics, as heating elements, in batteries, in the production of stain-resistant fabric, for bone grafting and dental implants, and for targeted drug delivery. Carbon nanofibers (CNFs) are strong, flexible fibers that are currently used to produce composite materials.Agitation can lead to aerosolized CNTs and CNFs, and peak airborne particulate concentrations are associated with workplace activities such as weighing, transferring, mixing, blending, or sonication. Most airborne CNTs or CNFs found in workplaces are loose agglomerates of micrometer diameter. However, due to their low density, they linger in workplace air for a considerable time, and a large fraction of these structures are respirable.In rat and mouse models, pulmonary exposure to single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), or CNFs causes the following pulmonary reactions: acute pulmonary inflammation and injury, rapid and persistent formation of granulomatous lesions at deposition sites of large CNT agglomerates, and rapid and progressive alveolar interstitial fibrosis at deposition sites of more dispersed CNT or CNF structures.Pulmonary exposure to SWCNTs can induce oxidant stress in aortic tissue and increases plaque formation in an atherosclerotic mouse model. Pulmonary exposure to MWCNTs depresses the ability of coronary arterioles to respond to dilators. These cardiovascular effects may result from neurogenic signals from sensory irritant receptors in the lung. Pulmonary exposure to MWCNTs also upregulates mRNA for inflammatory mediators in selected brain regions, and pulmonary exposure to SWCNTs upregulates the baroreceptor reflex. In addition, pulmonary exposure to MWCNTs may induce levels of inflammatory mediators in the blood, which may affect the cardiovascular system.

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Engineered Nanomaterials

Peters¹,

Grassian²

2010

Patty's Industrial Hygiene

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and Catalysis. He has been working in the environmental protection, multifunctional materials development, and analytical chemistry fields for 15 years and has a background of leading and managing large multidisciplinary, multi-partner research projects. He has been the author/co-author of more than 30 articles indexed in the Web of Science, Scopus, and other databases, 3 book chapters, and more than 60 participations in national and international scientific conferences. He has also filed 4 patents regarding materials development for ecofriendly processes.

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Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice

Cited by 1,193 publications

References 23 publications

Oops They Did It Again! Carbon Nanotubes Hoax Scientists in Viability Assays

Oops They Did It Again! Carbon Nanotubes Hoax Scientists in Viability Assays

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

Engineered Nanomaterials

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