Skip to main content

Advertisement

Log in

Role of oxidative stress in carbon nanotube-generated health effects

  • Review Article
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

The development of products containing carbon nanotubes (CNTs) is a major achievement of nanotechnology, although concerns regarding risk of toxic effects linger if the hazards associated with these materials are not thoroughly investigated. Exposure to CNTs has been associated with depletion of antioxidants, increased intracellular production of reactive oxygen species and pro-inflammatory signaling in cultured cells with primary function in the immune system as well as epithelial, endothelial and stromal cells. Pre-treatment with antioxidants has been shown to attenuate these effects, indicating a dependency of oxidative stress on cellular responses to CNT exposure. CNT-mediated oxidative stress in cell cultures has been associated with elevated levels of lipid peroxidation products and oxidatively damaged DNA. Investigations of oxidative stress endpoints in animal studies have utilized pulmonary, gastrointestinal, intravenous and intraperitoneal exposure routes, documenting elevated levels of lipid peroxidation products and oxidatively damaged DNA nucleobases especially in the lungs and liver, which to some extent occur concomitantly with altered levels of components in the antioxidant defense system (glutathione, superoxide dismutase or catalase). CNTs are biopersistent high aspect ratio materials, and some are rigid with lengths that lead to frustrated phagocytosis and pleural accumulation. There is accumulating evidence showing that pulmonary exposure to CNTs is associated with fibrosis and neoplastic changes in the lungs, and cardiovascular disease. As oxidative stress and inflammation responses are implicated in the development of these diseases, converging lines of evidence indicate that exposure to CNTs is associated with increased risk of cardiopulmonary diseases through generation of a pro-inflammatory and pro-oxidant milieu in the lungs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aiso S, Yamazaki K, Umeda Y, Asakura M, Kasai T, Takaya M, Toya T, Koda S, Nagano K, Arito H, Fukushima S (2010) Pulmonary toxicity of intratracheally instilled multiwall carbon nanotubes in male Fischer 344 rats. Ind Health 48:783–795

    PubMed  CAS  Google Scholar 

  • Alarifi S, Ali D, Verma A, Almajhdi FN, and Al-Qahtani AA (2014) Single-walled carbon nanotubes induce cytotoxicity and DNA damage via reactive oxygen species in human hepatocarcinoma cells. In Vitro Cell Dev Biol Anim. doi:10.1007/s11626-014-9760-3

  • Aldieri E, Fenoglio I, Cesano F, Gazzano E, Gulino G, Scarano D, Attanasio A, Mazzucco G, Ghigo D, Fubini B (2013) The role of iron impurities in the toxic effects exerted by short multiwalled carbon nanotubes (MWCNT) in murine alveolar macrophages. J Toxicol Environ Health A 76:1056–1071

    PubMed  CAS  Google Scholar 

  • Aschberger K, Johnston HJ, Stone V, Aitken RJ, Hankin SM, Peters SA, Tran CL, Christensen FM (2010) Review of carbon nanotubes toxicity and exposure–appraisal of human health risk assessment based on open literature. Crit Rev Toxicol 40:759–790

    PubMed  CAS  Google Scholar 

  • Barillet S, Simon-Deckers A, Herlin-Boime N, Mayne-L’Hermite M, Reynaud C, Cassio D, Gouget B, Carriere M (2010) Toxicological consequences of TiO2, SiC nanoparticles and multi-walled carbon nanotubes exposure in several mammalian cell types: an in vitro study. J Nanopart Res 12:61–73

    CAS  Google Scholar 

  • Barregard L, Møller P, Henriksen T, Mistry V, Koppen G, Rossner P, Sram R, Weimann A, Poulsen H, Nataf R, Andreolli R, Manini P, Marczylo TH, Lam P, Evans MD, Kasai H, Kawai K, Li YS, Sakai K, Singh R, Teichert F, Farmer P, Rozalski R, Gackowski D, Siomek A, Saez G, Cerda C, Broberg K, Lund C, Hossain M, Haghdoost S, Hu CW, Chao MR, Wu KY, Senduran N, Orhan H, Smith RJ, Santella R, Su Y, Cortez C, Yeh S, Olinski R, Loft S, Cooke MS (2013) Human and methodological sources of variability in the measurement of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine. Antioxid Redox Signal 18:2377–2391

    PubMed  CAS  PubMed Central  Google Scholar 

  • Bernstein DM (2007) Synthetic vitreous fibers: a review toxicology, epidemiology and regulations. Crit Rev Toxicol 37:839–886

    PubMed  CAS  Google Scholar 

  • Bihari P, Holzer M, Praetner M, Fent J, Lerchenberger M, Reichel CA, Rehberg M, Lakatos S, Krombach F (2010) Single-walled carbon nanotubes activate platelets and accelerate thrombus formation in the microcirculation. Toxicology 269:148–154

    PubMed  CAS  Google Scholar 

  • Breusing N, Grune T, Andrisic L, Atalay M, Bartosz G, Biasi F, Borovic S, Bravo L, Casals I, Casillas R, Dinischiotu A, Drzewinska J, Faber H, Fauzi NM, Gajewska A, Gambini J, Gradinaru D, Kokkola T, Lojek A, Luczaj W, Margina D, Mascia C, Mateos R, Meinitzer A, Mitjavila MT, Mrakovcic L, Munteanu MC, Podborska M, Poli G, Sicinska P, Skrzydlewska E, Vina J, Wiswedel I, Zarkovic N, Zelzer S, Spickett CM (2010) An inter-laboratory validation of methods of lipid peroxidation measurement in UVA-treated human plasma samples. Free Radic. Res. 44:1203–1215

    PubMed  CAS  Google Scholar 

  • Brown DM, Kinloch IA, Bangert U, Windle AH, Walter DM, Walker GS, Scotchford CA, Donaldson K, Stone V (2007) An in vitro study of the potential of carbon nanotubes and nanofibres to induce inflammatory mediators and frustrated phagocytosis. Carbon 45:1743–1756

    CAS  Google Scholar 

  • Burke AR, Singh RN, Carroll DL, Owen JD, Kock ND, D’Agostino R Jr, Torti FM, Torti SV (2011) Determinants of the thrombogenic potential of multiwalled carbon nanotubes. Biomaterials 32:5970–5978

    PubMed  CAS  PubMed Central  Google Scholar 

  • Cadet J, Loft S, Olinski R, Evans MD, Bialkowski K, Richard WJ, Dedon PC, Møller P, Greenberg MM, Cooke MS (2012) Biologically relevant oxidants and terminology, classification and nomenclature of oxidatively generated damage to nucleobases and 2-deoxyribose in nucleic acids. Free Radic Res 46:367–381

    PubMed  CAS  Google Scholar 

  • Cao Y, Jacobsen NR, Danielsen PH, Lenz AG, Stoeger T, Loft S, Wallin H, Roursgaard M, Mikkelsen L, Møller P (2014) Vascular effects of multi-walled carbon nanotubes in dyslipidemic ApoE / mice and cultured endothelial cells. Toxicol Sci 138:104–116

    PubMed  CAS  Google Scholar 

  • Carden DL, Granger DN (2000) Pathophysiology of ischaemia-reperfusion injury. J Pathol 190:255–266

    PubMed  CAS  Google Scholar 

  • Casey A, Herzog E, Lyng FM, Byrne HJ, Chambers G, Davoren M (2008) Single walled carbon nanotubes induce indirect cytotoxicity by medium depletion in A549 lung cells. Toxicol Lett 179:78–84

    PubMed  CAS  Google Scholar 

  • Cavallo D, Fanizza C, Ursini CL, Casciardi S, Paba E, Ciervo A, Fresegna AM, Maiello R, Marcelloni AM, Buresti G, Tombolini F, Bellucci S, Iavicoli S (2012) Multi-walled carbon nanotubes induce cytotoxicity and genotoxicity in human lung epithelial cells. J Appl Toxicol 32:454–464

    PubMed  CAS  Google Scholar 

  • Chen YR, Zweier JL (2014) Cardiac mitochondria and reactive oxygen species generation. Circ Res 114:524–537

    PubMed  CAS  PubMed Central  Google Scholar 

  • Chen B, Liu Y, Song WM, Hayashi Y, Ding XC, Li WH (2011) In vitro evaluation of cytotoxicity and oxidative stress induced by multiwalled carbon nanotubes in murine RAW 264.7 macrophages and human A549 lung cells. Biomed Environ Sci 24:593–601

    PubMed  CAS  Google Scholar 

  • Cheng WW, Lin ZQ, Ceng Q, Wei BF, Fan XJ, Zhang HS, Zhang W, Yang HL, Liu HL, Yan J, Tian L, Lin BC, Ding SM, Xi ZG (2012) Single-wall carbon nanotubes induce oxidative stress in rat aortic endothelial cells. Toxicol Mech Methods 22:268–276

    PubMed  CAS  Google Scholar 

  • Chou CC, Hsiao HY, Hong QS, Chen CH, Peng YW, Chen HW, Yang PC (2008) Single-walled carbon nanotubes can induce pulmonary injury in mouse model. Nano Lett 8:437–445

    PubMed  CAS  Google Scholar 

  • Cicchetti R, Divizia M, Valentini F, Argentin G (2011) Effects of single-wall carbon nanotubes in human cells of the oral cavity: geno-cytotoxic risk. Toxicol In Vitro 25:1811–1819

    PubMed  CAS  Google Scholar 

  • Clift MJ, Endes C, Vanhecke D, Wick P, Gehr P, Schins RP, Petri-Fink A, Rothen-Rutishauser B (2014) A comparative study of different in vitro lung cell culture systems to assess the most beneficial tool for screening the potential adverse effects of carbon nanotubes. Toxicol Sci 137:55–64

    PubMed  CAS  Google Scholar 

  • Collins AR, Dobson VL, Dusinska M, Kennedy G, Stetina R (1997) The comet assay: what can it really tell us? Mutat Res 375:183–193

    PubMed  CAS  Google Scholar 

  • Conner SD, Schmid SL (2003) Regulated portals of entry into the cell. Nature 422:37–44

    PubMed  CAS  Google Scholar 

  • Cooke MS, Loft S, Olinski R, Evans MD, Bialkowski K, Wagner JR, Dedon PC, Møller P, Greenberg MM, Cadet J (2010) Recommendations for standardized description of and nomenclature concerning oxidatively damaged nucleobases in DNA. Chem Res Toxicol 23:705–707

    PubMed  CAS  PubMed Central  Google Scholar 

  • Crimi E, Ignarro LJ, Napoli C (2007) Microcirculation and oxidative stress. Free Radic Res 41:1364–1375

    PubMed  CAS  Google Scholar 

  • Crouzier D, Follot S, Gentilhomme E, Flahaut E, Arnaud R, Dabouis V, Castellarin C, Debouzy JC (2010) Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung. Toxicology 272:39–45

    PubMed  CAS  Google Scholar 

  • Davoren M, Herzog E, Casey A, Cottineau B, Chambers G, Byrne HJ, Lyng FM (2007) In vitro toxicity evaluation of single walled carbon nanotubes on human A549 lung cells. Toxicol In Vitro 21:438–448

    PubMed  CAS  Google Scholar 

  • Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ (2005) Endothelial function and dysfunction. Part I: methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens 23:7–17

    PubMed  CAS  Google Scholar 

  • Di Giorgio ML, Di BS, Ragnelli AM, Aimola P, Santucci S, Poma A (2011) Effects of single and multi walled carbon nanotubes on macrophages: cyto and genotoxicity and electron microscopy. Mutat Res 722:20–31

    PubMed  Google Scholar 

  • Donaldson K, Aitken R, Tran L, Stone V, Duffin R, Forrest G, Alexander A (2006) Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 92:5–22

    PubMed  CAS  Google Scholar 

  • Donaldson K, Murphy FA, Duffin R, Poland CA (2010) Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Part Fibre Toxicol 7:5

    PubMed  PubMed Central  Google Scholar 

  • Donaldson K, Poland CA, Murphy FA, MacFarlane M, Chernova T, Schinwald A (2013) Pulmonary toxicity of carbon nanotubes and asbestos—similarities and differences. Adv Drug Deliv Rev 65:2078–2086

    PubMed  CAS  Google Scholar 

  • Dörger M, Munzing S, Allmeling AM, Krombach F (2000) Comparison of the phagocytic response of rat and hamster alveolar macrophages to man-made vitreous fibers in vitro. Hum Exp Toxicol 19:635–640

    PubMed  Google Scholar 

  • Dörger M, Munzing S, Allmeling AM, Messmer K, Krombach F (2001) Differential responses of rat alveolar and peritoneal macrophages to man-made vitreous fibers in vitro. Environ Res 85:207–214

    PubMed  Google Scholar 

  • Elgrabli D, Abella-Gallart S, Robidel F, Rogerieux F, Boczkowski J, Lacroix G (2008) Induction of apoptosis and absence of inflammation in rat lung after intratracheal instillation of multiwalled carbon nanotubes. Toxicology 253:131–136

    PubMed  CAS  Google Scholar 

  • Ema M, Masumori S, Kobayashi N, Naya M, Endoh S, Maru J, Hosoi M, Uno F, Nakajima M, Hayashi M, Nakanishi J (2013) In vivo comet assay of multi-walled carbon nanotubes using lung cells of rats intratracheally instilled. J Appl Toxicol 33:1053–1060

    PubMed  CAS  Google Scholar 

  • Erdely A, Hulderman T, Salmen R, Liston A, Zeidler-Erdely PC, Schwegler-Berry D, Castranova V, Koyama S, Kim YA, Endo M, Simeonova PP (2009) Cross-talk between lung and systemic circulation during carbon nanotube respiratory exposure. Potential biomarkers. Nano Lett 9:36–43

    PubMed  CAS  Google Scholar 

  • Erdely A, Liston A, Salmen-Muniz R, Hulderman T, Young SH, Zeidler-Erdely PC, Castranova V, Simeonova PP (2011) Identification of systemic markers from a pulmonary carbon nanotube exposure. J Occup Environ Med 53:S80–S86

    PubMed  CAS  Google Scholar 

  • ESCODD (European Standards Committee on Oxidative DNA Damage) (2003a) Comparative analysis of baseline 8-oxo-7,8-dihydroguanine in mammalian cell DNA, by different methods in different laboratories: an approach to consensus. Carcinogenesis 23:2129–2133

    Google Scholar 

  • ESCODD (European Standards Committee on Oxidative DNA Damage) (2003b) Measurement of DNA oxidation in human cells by chromatographic and enzymic methods. Free Radic Biol Med 34:1089–1099

    Google Scholar 

  • Evans MD, Dizdaroglu M, Cooke MS (2004) Oxidative DNA damage and disease: induction, repair and significance. Mutat Res 567:1–61

    PubMed  CAS  Google Scholar 

  • Fenoglio I, Tomatis M, Lison D, Muller J, Fonseca A, Nagy JB, Fubini B (2006) Reactivity of carbon nanotubes: free radical generation or scavenging activity? Free Radic Biol Med 40:1227–1233

    PubMed  CAS  Google Scholar 

  • Fischer-Nielsen A, Poulsen HE, Loft S (1992) 8-Hydroxydeoxyguanosine in vitro: effects of glutathione, ascorbate, and 5-aminosalicylic acid. Free Radic Biol Med 13:121–126

    PubMed  CAS  Google Scholar 

  • Foldbjerg R, Irving ES, Wang J, Thorsen K, Sutherland DS, Autrup H, Beer C (2014) The toxic effects of single-walled carbon nanotubes are linked to the phagocytic ability of cells. Toxicol Res 38:228–241

  • Folkmann JK, Risom L, Jacobsen NR, Wallin H, Loft S, Møller P (2009) Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes. Environ Health Perspect 117:703–708

    PubMed  CAS  PubMed Central  Google Scholar 

  • Fubini B, Ghiazza M, Fenoglio I (2010) Physico-chemical features of engineered nanoparticles relevant to their toxicity. Nanotoxicology 4:347–363

    PubMed  CAS  Google Scholar 

  • Gasser M, Wick P, Clift MJ, Blank F, Diener L, Yan B, Gehr P, Krug HF, Rothen-Rutishauser B (2012) Pulmonary surfactant coating of multi-walled carbon nanotubes (MWCNTs) influences their oxidative and pro-inflammatory potential in vitro. Part Fibre Toxicol 9:17

  • Ge C, Meng L, Xu L, Bai R, Du J, Zhang L, Li Y, Chang Y, Zhao Y, Chen C (2012) Acute pulmonary and moderate cardiovascular responses of spontaneously hypertensive rats after exposure to single-wall carbon nanotubes. Nanotoxicology 6:526–542

    PubMed  CAS  Google Scholar 

  • Gehrke TH, Lischke U, Gasteiger KL, Schneider S, Arnold S, Muller HC, Stephenson DS, Zipse H, Carell T (2013) Unexpected non-Hoogsteen-based mutagenicity mechanism of FaPy-DNA lesions. Nat Chem Biol 9:455–461

    PubMed  CAS  Google Scholar 

  • Gonzalez L, Lison D, Kirsch-Volders M (2009) Genotoxicity of engineered nanomaterials: a critical review. Nanotoxicology 2:252–273

    Google Scholar 

  • Gozzelino R, Jeney V, Soares MP (2010) Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol 50:323–354

    PubMed  CAS  Google Scholar 

  • Guo YY, Zhang J, Zheng YF, Yang J, Zhu XQ (2011) Cytotoxic and genotoxic effects of multi-wall carbon nanotubes on human umbilical vein endothelial cells in vitro. Mutat Res 721:184–191

    PubMed  CAS  Google Scholar 

  • Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142:231–255

    PubMed  CAS  PubMed Central  Google Scholar 

  • Han SG, Andrews R, Gairola CG, Bhalla DK (2008) Acute pulmonary effects of combined exposure to carbon nanotubes and ozone in mice. Inhal Toxicol 20:391–398

    PubMed  CAS  Google Scholar 

  • Han SG, Andrews R, Gairola CG (2010) Acute pulmonary response of mice to multi-wall carbon nanotubes. Inhal Toxicol 22:340–347

    PubMed  CAS  Google Scholar 

  • Han YG, Xu J, Li ZG, Ren GG, Yang Z (2012) In vitro toxicity of multi-walled carbon nanotubes in C6 rat glioma cells. Neurotoxicology 33:1128–1134

    PubMed  CAS  Google Scholar 

  • Hansson GK, Libby P (2006) The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 6:508–519

    PubMed  CAS  Google Scholar 

  • He XQ, Young SH, Schwegler-Berry D, Chisholm WP, Fernback JE, Ma Q (2011) Multiwalled carbon nanotubes induce a fibrogenic response by stimulating reactive oxygen species production, activating NF-kappa B signaling, and promoting fibroblast-to-myofibroblast transformation. Chem Res Toxicol 24:2237–2248

    PubMed  CAS  Google Scholar 

  • Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T (2001) Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 104:2673–2678

    PubMed  CAS  Google Scholar 

  • Helland A, Wick P, Koehler A, Schmid K, Som C (2007) Reviewing the environmental and human health knowledge base of carbon nanotubes. Environ Health Perspect 115:1125–1131

    PubMed  CAS  PubMed Central  Google Scholar 

  • Herzog E, Byrne HJ, Davoren M, Casey A, Duschl A, Oostingh GJ (2009) Dispersion medium modulates oxidative stress response of human lung epithelial cells upon exposure to carbon nanomaterial samples. Toxicol Appl Pharmacol 236:276–281

    PubMed  CAS  Google Scholar 

  • Hesterberg TW, Hart GA (2001) Synthetic vitreous fibers: a review of toxicology research and its impact on hazard classification. Crit Rev Toxicol 31:1–53

    PubMed  CAS  Google Scholar 

  • Holzer M, Bihari P, Praetner M, Uhl B, Reichel C, Fent J, Vippola M, Lakatos S, Krombach F (2014) Carbon-based nanomaterials accelerate arteriolar thrombus formation in the murine microcirculation independently of their shape. J Appl Toxicol. doi:10.1002/jat.2996

  • Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, Fitzgerald KA, Latz E (2008) Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9:847–856

    PubMed  CAS  PubMed Central  Google Scholar 

  • Houghton AM (2013) Mechanistic links between COPD and lung cancer. Nat Rev Cancer 13:233–245

    PubMed  CAS  Google Scholar 

  • Hu X, Cook S, Wang P, Hwang HM, Liu X, Williams QL (2010) In vitro evaluation of cytotoxicity of engineered carbon nanotubes in selected human cell lines. Sci Total Environ 408:1812–1817

    PubMed  CAS  Google Scholar 

  • Inoue K, Yanagisawa R, Koike E, Nishikawa M, Takano H (2010) Repeated pulmonary exposure to single-walled carbon nanotubes exacerbates allergic inflammation of the airway: possible role of oxidative stress. Free Radic Biol Med 48:924–934

    PubMed  CAS  Google Scholar 

  • Jacobsen NR, Pojana G, White P, Møller P, Cohn CA, Korsholm KS, Vogel U, Marcomini A, Loft S, Wallin H (2008) Genotoxicity, cytotoxicity and reactive oxygen species induced by single-walled carbon nanotubes and C60 fullerenes in the FE1-Muta™Mouse lung epithelial cells. Environ Mol Mutagen 49:476–487

    PubMed  CAS  Google Scholar 

  • Jacobsen NR, Møller P, Jensen JA, Vogel U, Ladefoged O, Loft S, Wallin H (2009) Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE−/− mice. Part Fibre Toxicol 6:2

    PubMed  PubMed Central  Google Scholar 

  • Jantzen K, Roursgaard M, Madsen CD, Loft S, Rasmussen LJ, Møller P (2012) Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures f human lung epithelial cells and macrophages. Mutagenesis 27:693–701

    PubMed  CAS  Google Scholar 

  • Ji Z, Zhang D, Li L, Shen X, Deng X, Dong L, Wu M, Liu Y (2009) The hepatotoxicity of multi-walled carbon nanotubes in mice. Nanotechnology 20:445101

    PubMed  Google Scholar 

  • Johnston HJ, Hutchison GR, Christensen FM, Peters S, Hankin S, Aschberger K, Stone V (2010) A critical review of the biological mechanisms underlying the in vivo and in vitro toxicity of carbon nanotubes: the contribution of physico-chemical characteristics. Nanotoxicology 4:207–246

    PubMed  CAS  Google Scholar 

  • Ju L, Zhang G, Zhang X, Jia Z, Gao X, Jiang Y, Yan C, Duerksen-Hughes PJ, Chen FF, Li H, Zhu X, Yang J (2014) Proteomic analysis of cellular response induced by multi-walled carbon nanotubes exposure in a549 cells. PLoS One 9:e84974

  • Kadiiska MB, Gladen BC, Baird DD, Germolec D, Graham LB, Parker CE, Nyska A, Wachsman JT, Ames BN, Basu S, Brot N, FitzGerald GA, Floyd RA, George M, Heinecke JW, Hatch GE, Hensley K, Lawson JA, Marnett LJ, Morrow JD, Murray DM, Plastaras J, Roberts LJ, Rokach J, Shigenaga MK, Sohal RS, Sun J, Tice RR, Van Thiel DH, Wellner D, Walter PB, Tomer KB, Mason RP, Barrett JC (2005) Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free Radic Biol Med 38:698–710

    PubMed  CAS  Google Scholar 

  • Kagan VE, Tyurina YY, Tyurin VA, Konduru NV, Potapovich AI, Osipov AN, Kisin ER, Schwegler-Berry D, Mercer R, Castranova V, Shvedova AA (2006) Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron. Toxicol Lett 165:88–100

    PubMed  CAS  Google Scholar 

  • Kagan VE, Kapralov AA, St Croix CM, Watkins SC, Kisin ER, Kotchey GP, Balasubramanian K, Vlasova II, Yu J, Kim K, Seo W, Mallampalli RK, Star A, Shvedova AA (2014) Lung macrophages “digest” carbon nanotubes using a superoxide/peroxynitrite oxidative pathway. ACS Nano 8:5610–5621

    PubMed  CAS  Google Scholar 

  • Kamiya H, Miura K, Ishikawa H, Inoue H, Nishimura S, Ohtsuka E (1992) c-Ha-ras containing 8-hydroxyguanine at codon 12 induces point mutations at the modified and adjacent positions. Cancer Res 52:3483–3485

    PubMed  CAS  Google Scholar 

  • Kanno S, Hirano S, Chiba S, Takeshita H, Nagai T, Takada M, Sakamoto K, Mukai T (2014) The role of Rho-kinases in IL-1beta release through phagocytosis of fibrous particles in human monocytes. Arch Toxicol. doi:10.1007/s00204-014-1238-2

  • Karlsson HL, Cronholm P, Gustafsson J, Moller L (2008) Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol 21:1726–1732

    PubMed  CAS  Google Scholar 

  • Kato T, Totsuka Y, Ishino K, Matsumoto Y, Tada Y, Nakae D, Goto S, Masuda S, Ogo S, Kawanishi M, Yagi T, Matsuda T, Watanabe M, Wakabayashi K (2013) Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay systems. Nanotoxicology 7:452–461

    PubMed  CAS  Google Scholar 

  • Kermanizadeh A, Gaiser BK, Hutchison GR, Stone V (2012) An in vitro liver model-assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials. Part Fibre Toxicol 9:28

    PubMed  CAS  PubMed Central  Google Scholar 

  • Kermanizadeh A, Vranic S, Boland S, Moreau K, Baeza-Squiban A, Gaiser BK, Andrzejczuk LA, Stone V (2013) An in vitro assessment of panel of engineered nanomaterials using a human renal cell line: cytotoxicity, pro-inflammatory response, oxidative stress and genotoxicity. BMC Nephrol 14:96

  • Kim JS, Sung JH, Song KS, Lee JH, Kim SM, Lee GH, Ahn KH, Lee JS, Shin JH, Park JD, Yu IJ (2012) Persistent DNA damage measured by comet assay of Sprague Dawley rat lung cells after five days of inhalation exposure and 1 month post-exposure to dispersed multi-wall carbon nanotubes (MWCNTs) generated by new MWCNT aerosol generation system. Toxicol Sci 128:439–448

    PubMed  CAS  Google Scholar 

  • Kim JS, Sung JH, Choi BG, Ryu HY, Song KS, Shin JH, Lee JS, Hwang JH, Lee JH, Lee GH, Jeon K, Ahn KH, Yu IJ (2014) In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure. Inhal Toxicol 26:222–234

    PubMed  Google Scholar 

  • Kisin ER, Murray AR, Keane MJ, Shi XC, Schwegler-Berry D, Gorelik O, Arepalli S, Castranova V, Wallace WE, Kagan VE, Shvedova AA (2007) Single-walled carbon nanotubes: geno- and cytotoxic effects in lung fibroblast V79 cells. J Toxicol Environ Health A 70:2071–2079

    PubMed  CAS  Google Scholar 

  • Kisin ER, Murray AR, Sargent L, Lowry D, Chirila M, Siegrist KJ, Schwegler-Berry D, Leonard S, Castranova V, Fadeel B, Kagan VE, Shvedova AA (2011) Genotoxicity of carbon nanofibers: are they potentially more or less dangerous than carbon nanotubes or asbestos? Toxicol Appl Pharmacol 252:1–10

    PubMed  CAS  Google Scholar 

  • Kleikers PW, Wingler K, Hermans JJ, Diebold I, Altenhofer S, Radermacher KA, Janssen B, Gorlach A, Schmidt HH (2012) NADPH oxidases as a source of oxidative stress and molecular target in ischemia/reperfusion injury. J Mol Med 90:1391–1406

    PubMed  CAS  Google Scholar 

  • Købler C, Saber AT, Jacobsen NR, Wallin H, Vogel U, Qvortrup K, Mølhave K (2014) FIB-SEM imaging of carbon nanotubes in mouse lung tissue. Anal Bioanal Chem 406:3863–3873

    PubMed  PubMed Central  Google Scholar 

  • Konduru NV, Tyurina YY, Feng W, Basova LV, Belikova NA, Bayir H, Clark K, Rubin M, Stolz D, Vallhov H, Scheynius A, Witasp E, Fadeel B, Kichambare PD, Star A, Kisin ER, Murray AR, Shvedova AA, Kagan VE (2009) Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes in vitro and in vivo. PLoS ONE 4:e4398

    PubMed  PubMed Central  Google Scholar 

  • Kosuge H, Sherlock SP, Kitagawa T, Dash R, Robinson JT, Dai H, McConnell MV (2012) Near infrared imaging and photothermal ablation of vascular inflammation using single-walled carbon nanotubes. J Am Heart Assoc 1:e002568

  • Kotchey GP, Zhao Y, Kagan VE, Star A (2013) Peroxidase-mediated biodegradation of carbon nanotubes in vitro and in vivo. Adv Drug Deliv Rev 65:1921–1932

    PubMed  CAS  Google Scholar 

  • Kumar A, Dhawan A (2013) Genotoxic and carcinogenic potential of engineered nanoparticles: an update. Arch Toxicol 87:1883–1900

    PubMed  CAS  Google Scholar 

  • Lam CW, James JT, McCluskey R, Hunter RL (2004) Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 77:126–134

    PubMed  CAS  Google Scholar 

  • Lam CW, James JT, McCluskey R, Arepalli S, Hunter RL (2006) A review of carbon nanotube toxicity and assessment of potential occupational and environmental health risks. Crit Rev Toxicol 36:189–217

    PubMed  CAS  Google Scholar 

  • Langrish JP, Bosson J, Unosson J, Muala A, Newby DE, Mills NL, Blomberg A, Sandstrom T (2012) Cardiovascular effects of particulate air pollution exposure: time course and underlying mechanisms. J Intern Med 272:224–239

    PubMed  CAS  Google Scholar 

  • Laursen JB, Somers M, Kurz S, McCann L, Warnholtz A, Freeman BA, Tarpey M, Fukai T, Harrison DG (2001) Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation 103:1282–1288

    PubMed  CAS  Google Scholar 

  • Le Page F, Margot A, Grollman AP, Sarasin A, Gentil A (1995) Mutagenicity of a 8-oxoguanine in a human Ha-ras sequence in mammalian cells. Carcinogenesis 16:2779–2784

    PubMed  Google Scholar 

  • Lee JK, Sayers BC, Chun KS, Lao HC, Shipley-Phillips JK, Bonner JC, Langenbach R (2012) Multi-walled carbon nanotubes induce COX-2 and iNOS expression via MAP kinase-dependent and -independent mechanisms in mouse RAW264.7 macrophages. Part Fibre Toxicol 9:14

    PubMed  CAS  PubMed Central  Google Scholar 

  • Legramante JM, Valentini F, Magrini A, Palleschi G, Sacco S, Iavicoli I, Pallante M, Moscone D, Galante A, Bergamaschi E, Bergamaschi A, Pietroiusti A (2009) Cardiac autonomic regulation after lung exposure to carbon nanotubes. Hum Exp Toxicol 28:369–375

    PubMed  CAS  Google Scholar 

  • Li JG, Li WX, Xu JY, Cai XQ, Liu RL, Li YJ, Zhao QF, Li QN (2007a) Comparative study of pathological lesions induced by multiwalled carbon nanotubes in lungs of mice by intratracheal instillation and inhalation. Environ Toxicol 22:415–421

    PubMed  CAS  Google Scholar 

  • Li Z, Hulderman T, Salmen R, Chapman R, Leonard SS, Young SH, Shvedova A, Luster MI, Simeonova PP (2007b) Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes. Environ Health Perspect 115:377–382

    PubMed  CAS  PubMed Central  Google Scholar 

  • Libby P, Ridker PM, Hansson GK (2011) Progress and challenges in translating the biology of atherosclerosis. Nature 473:17–325

    Google Scholar 

  • Lindberg HK, Falck GC, Suhonen S, Vippola M, Vanhala E, Catalan J, Savolainen K, Norppa H (2009) Genotoxicity of nanomaterials: DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibres in human bronchial epithelial cells in vitro. Toxicol Lett 186:166–173

    PubMed  CAS  Google Scholar 

  • Lindberg HK, Falck GC, Singh R, Suhonen S, Jarventaus H, Vanhala E, Catalan J, Farmer PB, Savolainen KM, Norppa H (2013) Genotoxicity of short single-wall and multi-wall carbon nanotubes in human bronchial epithelial and mesothelial cells in vitro. Toxicology 313:24–37

    PubMed  CAS  Google Scholar 

  • Liu D, Wang LJ, Wang ZG, Cuschieri A (2012) Different cellular response mechanisms contribute to the length-dependent cytotoxicity of multi-walled carbon nanotubes. Nanoscale Res Lett 7:361

    PubMed  PubMed Central  Google Scholar 

  • Loft S, Danielsen PH, Mikkelsen L, Risom L, Forchhammer L, Møller P (2008) Biomarkers of oxidative damage to DNA and repair. Biochem Soc Trans 36:1071–1076

    PubMed  CAS  Google Scholar 

  • Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426

    PubMed  CAS  Google Scholar 

  • Madl AK, Pinkerton KE (2009) Health effects of inhaled engineered and incidental nanoparticles. Crit Rev Toxicol 39:629–658

    PubMed  CAS  Google Scholar 

  • Ma-Hock L, Treumann S, Strauss V, Brill S, Luizi F, Mertler M, Wiench K, Gamer AO, van Ravenzwaay B, Landsiedel R (2009) Inhalation toxicity of multiwall carbon nanotubes in rats exposed for 3 months. Toxicol Sci 112:468–481

    PubMed  CAS  Google Scholar 

  • Mangum JB, Turpin EA, Antao-Menezes A, Cesta MF, Bermudez E, Bonner JC (2006) Single-walled carbon nanotube (SWCNT)-induced interstitial fibrosis in the lungs of rats is associated with increased levels of PDGF mRNA and the formation of unique intercellular carbon structures that bridge alveolar macrophages in situ. Part Fibre Toxicol 3:15

    PubMed  PubMed Central  Google Scholar 

  • Mann EE, Thompson LC, Shannahan JH, Wingard CJ (2012) Changes in cardiopulmonary function induced by nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol 4:691–702

    PubMed  CAS  PubMed Central  Google Scholar 

  • Manna SK, Sarkar S, Barr J, Wise K, Barrera EV, Jejelowo O, Rice-Ficht AC, Ramesh GT (2005) Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-kappaB in human keratinocytes. Nano Lett 5:1676–1684

    PubMed  CAS  PubMed Central  Google Scholar 

  • Manshian BB, Jenkins GJS, Williams PM, Wright C, Barron AR, Brown AP, Hondow N, Dunstan PR, Rickman R, Brady K, Doak SH (2013) Single-walled carbon nanotubes: differential genotoxic potential associated with physico-chemical properties. Nanotoxicology 7:144–156

    PubMed  CAS  Google Scholar 

  • McShan D, Yu H (2012) DNA damage in human skin keratinocytes caused by multiwalled carbon nanotubes with carboxylate functionalization. Ind Health, Toxicol. doi:10.1177/0748233712459914

    Google Scholar 

  • Mercer RR, Scabilloni J, Wang L, Kisin E, Murray AR, Schwegler-Berry D, Shvedova AA, Castranova V (2008) Alteration of deposition pattern and pulmonary response as a result of improved dispersion of aspirated single-walled carbon nanotubes in a mouse model. Am J Physiol Lung Cell Mol Physiol 294:L87–L97

    PubMed  CAS  Google Scholar 

  • Mercer RR, Hubbs AF, Scabilloni JF, Wang L, Battelli LA, Schwegler-Berry D, Castranova V, Porter DW (2010) Distribution and persistence of pleural penetrations by multi-walled carbon nanotubes. Part Fibre Toxicol 7:28

    PubMed  PubMed Central  Google Scholar 

  • Mercer RR, Scabilloni JF, Hubbs AF, Battelli LA, McKinney W, Friend S, Wolfarth MG, Andrew M, Castranova V, Porter DW (2013a) Distribution and fibrotic response following inhalation exposure to multi-walled carbon nanotubes. Part Fibre Toxicol 10:33

    PubMed  CAS  PubMed Central  Google Scholar 

  • Mercer RR, Scabilloni JF, Hubbs AF, Wang L, Battelli LA, McKinney W, Castranova V, Porter DW (2013b) Extrapulmonary transport of MWCNT following inhalation exposure. Part Fibre Toxicol 10:38

    PubMed  CAS  PubMed Central  Google Scholar 

  • Migliore L, Saracino D, Bonelli A, Colognato R, D’Errico MR, Magrini A, Bergamaschi A, Bergamaschi E (2010) Carbon nanotubes induce oxidative DNA damage in RAW 264.7 cells. Environ Mol Mutagen 51:294–303

    PubMed  CAS  Google Scholar 

  • Mitchell LA, Gao J, Wal RV, Gigliotti A, Burchiel SW, McDonald JD (2007) Pulmonary and systemic immune response to inhaled multiwalled carbon nanotubes. Toxicol Sci 100:203–214

    PubMed  CAS  Google Scholar 

  • Mohiuddin KekaIS, Evans TJ, Hirota K, Shimizu H, Kono K, Takeda S, Hirano S (2014) A novel genotoxicity assay of carbon nanotubes using functional macrophage receptor with collagenous structure (MARCO)-expressing chicken B lymphocytes. Arch Toxicol 88:145–160

    PubMed  CAS  Google Scholar 

  • Møller P (2005) Genotoxicity of environmental agents assessed by the alkaline comet assay. Basic Clin Pharmacol Toxicol 96(supplement 1):1–42

    PubMed  Google Scholar 

  • Møller P, Loft S (2010) Oxidative damage to DNA and lipids as biomarkers of exposure to air pollution. Environ Health Perspect 118:1126–1136

    PubMed  PubMed Central  Google Scholar 

  • Møller P, Jacobsen NR, Folkmann JK, Danielsen PH, Mikkelsen L, Hemmingsen JG, Vesterdal LK, Forchhammer L, Wallin H, Loft S (2010) Role of oxidative damage in toxicity of particulates. Free Radic Res 44:1–46

    PubMed  Google Scholar 

  • Møller P, Mikkelsen L, Vesterdal LK, Folkmann JK, Forchhammer L, Roursgaard M, Danielsen PH, Loft S (2011) Hazard identification of particulate matter on vasomotor dysfunction and progression of atherosclerosis. Crit Rev Toxicol 41:339–368

    PubMed  Google Scholar 

  • Møller P, Cooke MS, Collins A, Olinski R, Rozalski R, Loft S (2012) Harmonising measurements of 8-oxo-7,8-dihydro-2′-deoxyguanosine in cellular DNA and urine. Free Radic Res 46:541–553

    PubMed  Google Scholar 

  • Monteiro-Riviere NA, Nemanich RJ, Inman AO, Wang YY, Riviere JE (2005) Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicol Lett 155:377–384

    PubMed  CAS  Google Scholar 

  • Morimoto Y, Hirohashi M, Kobayashi N, Ogami A, Horie M, Oyabu T, Myojo T, Hashiba M, Mizuguchi Y, Kambara T, Lee BW, Kuroda E, Shimada M, Wang WN, Mizuno K, Yamamoto K, Fujita K, Nakanishi J, Tanaka I (2012) Pulmonary toxicity of well-dispersed single-wall carbon nanotubes after inhalation. Nanotoxicology 6:766–775

    PubMed  CAS  Google Scholar 

  • Moriya M (1993) Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-oxoguanine in DNA induces targeted G:C–T:A transversions in simian kidney cells. Proc Natl Acad Sci USA 90:1122–1126

    PubMed  CAS  PubMed Central  Google Scholar 

  • Muller J, Huaux F, Moreau N, Misson P, Heilier JF, Delos M, Arras M, Fonseca A, Nagy JB, Lison D (2005) Respiratory toxicity of multi-wall carbon nanotubes. Toxicol Appl Pharmacol 207:221–231

    PubMed  CAS  Google Scholar 

  • Muller J, Delos M, Panin N, Rabolli V, Huaux F, Lison D (2009) Absence of carcinogenic response to multiwall carbon nanotubes in a 2-year bioassay in the peritoneal cavity of the rat. Toxicol Sci 110:442–448

    PubMed  CAS  Google Scholar 

  • Müller L, Riediker M, Wick P, Mohr M, Gehr P, Rothen-Rutishauser B (2010) Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways. J R Soc Interface 7(Suppl 1):S27–S40

  • Murphy FA, Schinwald A, Poland CA, Donaldson K (2012) The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells. Part Fibre Toxicol 9:8

    PubMed  CAS  PubMed Central  Google Scholar 

  • Murray AR, Kisin ER, Tkach AV, Yanamala N, Mercer RR, Young SH, Fadeel B, Kagan VE, Shvedova AA (2012) Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos. Part Fibre Toxicol 9:10

    PubMed  CAS  PubMed Central  Google Scholar 

  • Nagai H, Okazaki Y, Chew SH, Misawa N, Yamashita Y, Akatsuka S, Ishihara T, Yamashita K, Yoshikawa Y, Yasui H, Jiang L, Ohara H, Takahashi T, Ichihara G, Kostarelos K, Miyata Y, Shinohara H, Toyokuni S (2011) Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis. Proc Natl Acad Sci USA 108:E1330–E1338

    PubMed  PubMed Central  Google Scholar 

  • Nagai H, Okazaki Y, Chew SH, Misawa N, Miyata Y, Shinohara H, Toyokuni S (2013) Intraperitoneal administration of tangled multiwalled carbon nanotubes of 15 nm in diameter does not induce mesothelial carcinogenesis in rats. Pathol Int 63:457–462

    PubMed  CAS  Google Scholar 

  • Naya M, Kobayashi N, Endoh S, Maru J, Honda K, Ema M, Tanaka J, Fukumuro M, Hasegawa K, Nakajima M, Hayashi M, Nakanishi J (2012) In vivo genotoxicity study of single-wall carbon nanotubes using comet assay following intratracheal instillation in rats. Regul Toxicol Pharmacol 64:124–129

    PubMed  CAS  Google Scholar 

  • Nemmar A, Hoet PH, Vandervoort P, Dinsdale D, Nemery B, Hoylaerts MF (2007) Enhanced peripheral thrombogenicity after lung inflammation is mediated by platelet-leukocyte activation: role of P-selectin. J Thromb Haemost 5:1217–1226

  • Nordenfelt P, Tapper H (2011) Phagosome dynamics during phagocytosis by neutrophils. J Leukoc Biol 90:271–284

    PubMed  CAS  Google Scholar 

  • Nunes P, Demaurex N, Dinauer MC (2013) Regulation of the NADPH oxidase and associated ion fluxes during phagocytosis. Traffic 14:1118–1131

    PubMed  CAS  Google Scholar 

  • Nymark P, Jensen KA, Suhonen S, Kembouche Y, Vippola M, Kleinjans J, Catalan J, Norppa H, van Delft J, Briede JJ (2014) Free radical scavenging and formation by multi-walled carbon nanotubes in cell free conditions and in human bronchial epithelial cells. Part Fibre Toxicol 11:4

    PubMed  PubMed Central  Google Scholar 

  • Oberdörster G (2002) Toxicokinetics and effects of fibrous and nonfibrous particles. Inhal Toxicol 14:29–56

    PubMed  Google Scholar 

  • Ogasawara Y, Umezu N, Ishii K (2012) DNA damage in human pleural mesothelial cells induced by exposure to carbon nanotubes. Nihon Eiseigaku Zasshi 67:76–83

    PubMed  CAS  Google Scholar 

  • Pacurari M, Yin XJ, Zhao J, Ding M, Leonard SS, Schwegler-Berry D, Ducatman BS, Sbarra D, Hoover MD, Castranova V, Vallyathan V (2008) Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells. Environ Health Perspect 116:1211–1217

    PubMed  CAS  PubMed Central  Google Scholar 

  • Pacurari M, Qian Y, Fu W, Schwegler-Berry D, Ding M, Castranova V, Guo NL (2012) Cell permeability, migration, and reactive oxygen species induced by multiwalled carbon nanotubes in human microvascular endothelial cells. J Toxicol Environ Health A 75:112–128

    PubMed  CAS  PubMed Central  Google Scholar 

  • Palomaki J, Valimaki E, Sund J, Vippola M, Clausen PA, Jensen KA, Savolainen K, Matikainen S, Alenius H (2011) Long, needle-like carbon nanotubes and asbestos activate the NLRP3 inflammasome through a similar mechanism. ACS Nano 5:6861–6870

    PubMed  CAS  Google Scholar 

  • Patlolla AK, Hussain SM, Schlager JJ, Patlolla S, Tchounwou PB (2010) Comparative study of the clastogenicity of functionalized and nonfunctionalized multiwalled carbon nanotubes in bone marrow cells of Swiss-Webster mice. Environ Toxicol 25:608–621

    PubMed  CAS  PubMed Central  Google Scholar 

  • Patlolla AK, Berry A, Tchounwou PB (2011) Study of hepatotoxicity and oxidative stress in male Swiss-Webster mice exposed to functionalized multi-walled carbon nanotubes. Mol Cell Biochem 358:189–199

    PubMed  CAS  PubMed Central  Google Scholar 

  • Pauluhn J (2010) Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures. Toxicol Sci 113:226–242

    PubMed  CAS  Google Scholar 

  • Pauluhn J (2014) The metrics of MWCNT-induced pulmonary inflammation are dependent on the selected testing regimen. Regul Toxicol Pharmacol 68:343–352

    PubMed  Google Scholar 

  • Pelka J, Gehrke H, Rechel A, Kappes M, Hennrich F, Hartinger CG, Marko D (2013) DNA damaging properties of single walled carbon nanotubes in human colon carcinoma cells. Nanotoxicology 7:2–20

    PubMed  CAS  Google Scholar 

  • Pichardo S, Gutierrez-Praena D, Puerto M, Sanchez E, Grilo A, Camean AM, Jos A (2012) Oxidative stress responses to carboxylic acid functionalized single wall carbon nanotubes on the human intestinal cell line Caco-2. Toxicol In Vitro 26:672–677

    PubMed  CAS  Google Scholar 

  • Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WAH, Seaton A, Stone V, Brown S, MacNee W, Donaldson K (2008) Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotechnol 3:423–428

    PubMed  CAS  Google Scholar 

  • Porter DW, Hubbs AF, Chen BT, McKinney W, Mercer RR, Wolfarth MG, Battelli L, Wu N, Sriram K, Leonard S, Andrew M, Willard P, Tsuruoka S, Endo M, Tsukada T, Munekane F, Frazer DG, Castranova V (2013) Acute pulmonary dose-responses to inhaled multi-walled carbon nanotubes. Nanotoxicology 7:1179–1194

    PubMed  CAS  Google Scholar 

  • Pulskamp K, Diabate S, Krug HF (2007) Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants. Toxicol Lett 168:58–74

    PubMed  CAS  Google Scholar 

  • Radomski A, Jurasz P, Alonso-Escolano D, Drews M, Morandi M, Malinski T, Radomski MW (2005) Nanoparticle-induced platelet aggregation and vascular thrombosis. Br J Pharmacol 146:882–893

    PubMed  CAS  PubMed Central  Google Scholar 

  • Ravichandran P, Baluchamy S, Sadanandan B, Gopikrishnan R, Biradar S, Ramesh V, Hall JC, Ramesh GT (2010) Multiwalled carbon nanotubes activate NF-kappaB and AP-1 signaling pathways to induce apoptosis in rat lung epithelial cells. Apoptosis 15:1507–1516

    PubMed  CAS  Google Scholar 

  • Reddy AR, Reddy YN, Krishna DR, Himabindu V (2010) Multi wall carbon nanotubes induce oxidative stress and cytotoxicity in human embryonic kidney (HEK293) cells. Toxicology 272:11–16

    PubMed  CAS  Google Scholar 

  • Reddy ARN, Reddy YN, Himabindu V, Krishna DR (2011) Induction of oxidative stress and cytotoxicity by carbon nanomaterials is dependent on physical properties. Toxicol Ind Health 27:3–10

    CAS  Google Scholar 

  • Risom L, Møller P, Vogel U, Kristjansen PEG, Loft S (2003) X-ray-induced oxidative stress: DNA damage and gene expression of HO-1, ERCC1 and OGG1 in mouse lung. Free Rad Res 37:957–966

    CAS  Google Scholar 

  • Ronzani C, Spiegelhalter C, Vonesch JL, Lebeau L, Pons F (2012) Lung deposition and toxicological responses evoked by multi-walled carbon nanotubes dispersed in a synthetic lung surfactant in the mouse. Arch Toxicol 86:137–149

    PubMed  CAS  Google Scholar 

  • Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126

    PubMed  CAS  Google Scholar 

  • Ryman-Rasmussen JP, Cesta MF, Brody AR, Shipley-Phillips JK, Everitt JI, Tewksbury EW, Moss OR, Wong BA, Dodd DE, Andersen ME, Bonner JC (2009a) Inhaled carbon nanotubes reach the subpleural tissue in mice. Nat Nanotechnol 4:747–751

    PubMed  CAS  PubMed Central  Google Scholar 

  • Ryman-Rasmussen JP, Tewksbury EW, Moss OR, Cesta MF, Wong BA, Bonner JC (2009b) Inhaled multiwalled carbon nanotubes potentiate airway fibrosis in murine allergic asthma. Am J Respir Cell Mol Biol 40:349–358

    PubMed  CAS  PubMed Central  Google Scholar 

  • Sakamoto Y, Nakae D, Fukumori N, Tayama K, Maekawa A, Imai K, Hirose A, Nishimura T, Ohashi N, Ogata A (2009) Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats. J Toxicol Sci 34:65–76

    PubMed  CAS  Google Scholar 

  • Sargent LM, Porter DW, Staska LM, Hubbs AF, Lowry DT, Battelli L, Siegrist KJ, Kashon ML, Mercer RR, Bauer AK, Chen BT, Salisbury JL, Frazer D, McKinney W, Andrew M, Tsuruoka S, Endo M, Fluharty KL, Castranova V, Reynolds SH (2014) Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes. Part Fibre Toxicol 11:3

    PubMed  PubMed Central  Google Scholar 

  • Sarkar S, Sharma C, Yog R, Periakaruppan A, Jejelowo O, Thomas R, Barrera EV, Rice-Ficht AC, Wilson BL, Ramesh GT (2007) Analysis of stress responsive genes induced by single-walled carbon nanotubes in BJ Foreskin cells. J Nanosci Nanotechnol 7:584–592

    PubMed  CAS  PubMed Central  Google Scholar 

  • Sauer UG, Vogel S, Aumann A, Hess A, Kolle SN, Ma-Hock L, Wohlleben W, Dammann M, Strauss V, Treumann S, Groters S, Wiench K, van Ravenzwaay B, Landsiedel R (2014) Applicability of rat precision-cut lung slices in evaluating nanomaterial cytotoxicity, apoptosis, oxidative stress, and inflammation. Toxicol Appl Pharmacol 276:1–20

    PubMed  CAS  Google Scholar 

  • Schinwald A, Donaldson K (2012) Use of back-scatter electron signals to visualise cell/nanowires interactions in vitro and in vivo; frustrated phagocytosis of long fibres in macrophages and compartmentalisation in mesothelial cells in vivo. Part Fibre Toxicol 9:34

    PubMed  CAS  PubMed Central  Google Scholar 

  • Schinwald A, Murphy FA, Prina-Mello A, Poland CA, Byrne F, Movia D, Glass JR, Dickerson JC, Schultz DA, Jeffree CE, MacNee W, Donaldson K (2012) The threshold length for fiber-induced acute pleural inflammation: shedding light on the early events in asbestos-induced mesothelioma. Toxicol Sci 128:461–470

    PubMed  CAS  Google Scholar 

  • Schrand AM, Dai L, Schlager JJ, Hussain SM, Osawa E (2007) Differential biocompatibility of carbon nanotubes and nanodiamonds. Diam Relat Mater 16:2118–2123

    CAS  Google Scholar 

  • Semberova J, De Paoli Lacerda SH, Simakova O, Holada K, Gelderman MP, Simak J (2009) Carbon nanotubes activate blood platelets by inducing extracellular Ca2+ influx sensitive to calcium entry inhibitors. Nano Lett 9:3312–3317

    PubMed  CAS  Google Scholar 

  • Shvedova AA, Castranova V, Kisin ER, Schwegler-Berry D, Murray AR, Gandelsman VZ, Maynard A, Baron P (2003) Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocyte cells. J Toxicol Environ Health A 66:1909–1926

    PubMed  CAS  Google Scholar 

  • Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P (2005) Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 289:L698–L708

    PubMed  CAS  Google Scholar 

  • Shvedova AA, Kisin ER, Murray AR, Gorelik O, Arepalli S, Castranova V, Young SH, Gao F, Tyurina YY, Oury TD, Kagan VE (2007) Vitamin E deficiency enhances pulmonary inflammatory response and oxidative stress induced by single-walled carbon nanotubes in C57BL/6 mice. Toxicol Appl Pharmacol 221:339–348

    PubMed  CAS  PubMed Central  Google Scholar 

  • Shvedova AA, Kisin E, Murray AR, Johnson VJ, Gorelik O, Arepalli S, Hubbs AF, Mercer RR, Keohavong P, Sussman N, Jin J, Yin J, Stone S, Chen BT, Deye G, Maynard A, Castranova V, Baron PA, Kagan VE (2008a) Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. Am J Physiol Lung Cell Mol Physiol 295:L552–L565

    PubMed  CAS  PubMed Central  Google Scholar 

  • Shvedova AA, Kisin ER, Murray AR, Kommineni C, Castranova V, Fadeel B, Kagan VE (2008b) Increased accumulation of neutrophils and decreased fibrosis in the lung of NADPH oxidase-deficient C57BL/6 mice exposed to carbon nanotubes. Toxicol Appl Pharmacol 231:235–240

    PubMed  CAS  Google Scholar 

  • Shvedova AA, Pietroiusti A, Fadeel B, Kagan VE (2012) Mechanisms of carbon nanotube-induced toxicity: focus on oxidative stress. Toxicol Appl Pharmacol 261:121–133

    PubMed  CAS  Google Scholar 

  • Simon-Deckers A, Gouget B, Mayne-L’Hermite M, Herlin-Boime N, Reynaud C, Carriere M (2008) In vitro investigation of oxide nanoparticle and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes. Toxicology 253:137–146

    PubMed  CAS  Google Scholar 

  • Singh NP, Tice RR, Stephens RE, Schneider EL (1991) A microgel electroforesis technique for the quantitation of DNA damage and repair in individual fibroblasts cultured on microscope slides. Mutat Res 252:289–296

    PubMed  CAS  Google Scholar 

  • Snyder-Talkington BN, Schwegler-Berry D, Castranova V, Qian Y, Guo NL (2013) Multi-walled carbon nanotubes induce human microvascular endothelial cellular effects in an alveolar-capillary co-culture with small airway epithelial cells. Part Fibre Toxicol 10:35

    PubMed  CAS  PubMed Central  Google Scholar 

  • Spickett CM, Wiswedel I, Siems W, Zarkovic K, Zarkovic N (2010) Advances in methods for the determination of biologically relevant lipid peroxidation products. Free Radic Res 44:1172–1202

    PubMed  CAS  Google Scholar 

  • Srivastava RK, Pant AB, Kashyap MP, Kumar V, Lohani M, Jonas L, Rahman Q (2011) Multi-walled carbon nanotubes induce oxidative stress and apoptosis in human lung cancer cell line-A549. Nanotoxicology 5:195–207

    PubMed  CAS  Google Scholar 

  • Stapleton PA, Minarchick VC, Cumpston AM, McKinney W, Chen BT, Sager TM, Frazer DG, Mercer RR, Scabilloni J, Andrew ME, Castranova V, Nurkiewicz TR (2012) Impairment of coronary arteriolar endothelium-dependent dilation after multi-walled carbon nanotube inhalation: a time-course study. Int J Mol Sci 13:13781–13803

    PubMed  CAS  PubMed Central  Google Scholar 

  • Stone V, Johnston H, Schins RP (2009) Development of in vitro systems for nanotoxicology: methodological considerations. Crit Rev Toxicol 39:613–626

    PubMed  CAS  Google Scholar 

  • Tabet L, Bussy C, Amara N, Setyan A, Grodet A, Rossi MJ, Pairon JC, Boczkowski J, Lanone S (2009) Adverse effects of industrial multiwalled carbon nanotubes on human pulmonary cells. J Toxicol Environ Health A 72:60–73

    PubMed  CAS  PubMed Central  Google Scholar 

  • Takagi A, Hirose A, Nishimura T, Fukumori N, Ogata A, Ohashi N, Kitajima S, Kanno J (2008) Induction of mesothelioma in p53 ± mouse by intraperitoneal application of multi-wall carbon nanotube. J Toxicol Sci 33:105–116

    PubMed  CAS  Google Scholar 

  • Takagi A, Hirose A, Futakuchi M, Tsuda H, Kanno J (2012) Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice. Cancer Sci 103:1440–1444

    PubMed  CAS  PubMed Central  Google Scholar 

  • Tan X, Grollman AP, Shibutani S (1999) Comparison of the mutagenic properties of 8-oxo-7,8-dihydro-2′-deoxyadenosine and 8-oxo-7,8-dihydro-2′-deoxyguanosine DNA lesions in mammalian cells. Carcinogenesis 20:2287–2292

    PubMed  CAS  Google Scholar 

  • Thompson LC, Frasier CR, Sloan RC, Mann EE, Harrison BS, Brown JM, Brown DA, Wingard CJ (2014) Pulmonary instillation of multi-walled carbon nanotubes promotes coronary vasoconstriction and exacerbates injury in isolated hearts. Nanotoxicology 8:38–49

    PubMed  CAS  Google Scholar 

  • Thurnherr T, Su DS, Diener L, Weinberg G, Manser P, Pfander N, Arrigo R, Schuster ME, Wick P, Krug HF (2009) Comprehensive evaluation of in vitro toxicity of three large-scale produced carbon nanotubes on human Jurkat T cells and a comparison to crocidolite asbestos. Nanotoxicology 3:319–338

    CAS  Google Scholar 

  • Thurnherr T, Brandenberger C, Fischer K, Diener L, Manser P, Maeder-Althaus X, Kaiser JP, Krug HF, Rothen-Rutishauser B, Wick P (2011) A comparison of acute and long-term effects of industrial multiwalled carbon nanotubes on human lung and immune cells in vitro. Toxicol Lett 200:176–186

    PubMed  CAS  Google Scholar 

  • Tong H, McGee JK, Saxena RK, Kodavanti UP, Devlin RB, Gilmour MI (2009) Influence of acid functionalization on the cardiopulmonary toxicity of carbon nanotubes and carbon black particles in mice. Toxicol Appl Pharmacol 239:224–232

    PubMed  CAS  Google Scholar 

  • Tsukahara T, Matsuda Y, Usui Y, Haniu H (2013) Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in human lung cells. Biochem Biophys Res Commun 440:348–353

    PubMed  CAS  Google Scholar 

  • Urankar RN, Lust RM, Mann E, Katwa P, Wang X, Podila R, Hilderbrand SC, Harrison BS, Chen P, Ke PC, Rao AM, Brown JM, Wingard CJ (2012) Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes. Part Fibre Toxicol 9:38

    PubMed  CAS  PubMed Central  Google Scholar 

  • van Berlo D, Clift MJ, Albrecht C, Schins RP (2012) Carbon nanotubes: an insight into the mechanisms of their potential genotoxicity. Swiss Med Wkly 142:w13698

    PubMed  Google Scholar 

  • van Berlo D, Wilhelmi V, Boots AW, Hullmann M, Kuhlbusch TA, Bast A, Schins RP, Albrecht C (2014) Apoptotic, inflammatory, and fibrogenic effects of two different types of multi-walled carbon nanotubes in mouse lung. Arch Toxicol 88:1725–1737

  • Vanhoutte PM (2009) Endothelial dysfunction: the first step toward coronary arteriosclerosis. Circ J 73:595–601

    PubMed  CAS  Google Scholar 

  • Varga C, Szendi K (2010) Carbon nanotubes induce granulomas but not mesotheliomas. In Vivo 24:153–156

    PubMed  Google Scholar 

  • Vesterdal LK, Danielsen PH, Folkmann JK, Jespersen LF, Aguilar-Pelaez K, Roursgaard M, Loft S, Møller P (2014a) Accumulation of lipids and oxidatively damaged DNA in hepatocytes exposed to particles. Toxicol Appl Pharmacol 274:350–360

    PubMed  CAS  Google Scholar 

  • Vesterdal LK, Jantzen K, Sheykhzade M, Roursgaard M, Folkmann JK, Loft S, Møller P (2014b) Pulmonary exposure to particles from diesel exhaust, urban dust or single-walled carbon nanotubes and oxidatively damaged DNA and vascular function in apoE(−/−)mice. Nanotoxicology 8:61–71

    PubMed  CAS  Google Scholar 

  • Vidanapathirana AK, Lai X, Hilderbrand SC, Pitzer JE, Podila R, Sumner SJ, Fennell TR, Wingard CJ, Witzmann FA, Brown JM (2012) Multi-walled carbon nanotube directed gene and protein expression in cultured human aortic endothelial cells is influenced by suspension medium. Toxicology 302:114–122

    PubMed  CAS  PubMed Central  Google Scholar 

  • Violi F, Pignatelli P (2012) Platelet oxidative stress and thrombosis. Thromb Res 129:378–381

    PubMed  CAS  Google Scholar 

  • Vittorio O, Raffa V, Cuschieri A (2009) Influence of purity and surface oxidation on cytotoxicity of multiwalled carbon nanotubes with human neuroblastoma cells. Nanomedicine 5:424–431

    PubMed  CAS  Google Scholar 

  • Wang QE, Han CH, Yang YP, Wang HB, Wu WD, Liu SJ, Kohyama N (1999) Biological effects of man-made mineral fibers (II)—their genetic damages examined by in vitro assay. Ind Health 37:342–347

    PubMed  CAS  Google Scholar 

  • Wang X, Katwa P, Podila R, Chen P, Ke PC, Rao AM, Walters DM, Wingard CJ, Brown JM (2011) Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6 mice. Part Fibre Toxicol 8:24

    PubMed  PubMed Central  Google Scholar 

  • Warheit DB, Laurence BR, Reed KL, Roach DH, Reynolds GA, Webb TR (2004) Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol Sci 77:117–125

    PubMed  CAS  Google Scholar 

  • Widlansky ME, Gokce N, Keaney JF Jr, Vita JA (2003) The clinical implications of endothelial dysfunction. J Am Coll Cardiol 42:1149–1160

    PubMed  CAS  Google Scholar 

  • Winczura A, Zdzalik D, Tudek B (2012) Damage of DNA and proteins by major lipid peroxidation products in genome stability. Free Radic Res 46:442–459

    PubMed  CAS  Google Scholar 

  • Xu H, Bai J, Meng J, Hao W, Xu H, Cao JM (2009) Multi-walled carbon nanotubes suppress potassium channel activities in PC12 cells. Nanotechnology 20:285102

  • Xu YY, Yang J, Shen T, Zhou F, Xia Y, Fu JY, Meng J, Zhang J, Zheng YF, Yang J, Xu LH, Zhu XQ (2012) Intravenous administration of multi-walled carbon nanotubes affects the formation of atherosclerosis in Sprague–Dawley rats. J Occup Health. doi:10.1539/joh.12-0019-OA

  • Xu J, Alexander DB, Futakuchi M, Numano T, Fukamachi K, Suzui M, Omori T, Kanno J, Hirose A, Tsuda H (2014) Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes. Cancer Sci 105:763–769

  • Yamashita K, Yoshioka Y, Higashisaka K, Morishita Y, Yoshida T, Fujimura M, Kayamuro H, Nabeshi H, Yamashita T, Nagano K, Abe Y, Kamada H, Kawai Y, Mayumi T, Yoshikawa T, Itoh N, Tsunoda S, Tsutsumi Y (2010) Carbon nanotubes elicit DNA damage and inflammatory response relative to their size and shape. Inflammation 33:276–280

    PubMed  CAS  Google Scholar 

  • Yang H, Liu C, Yang D, Zhang H, Xi Z (2008a) Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition. J Appl Toxicol 29:69–78

    Google Scholar 

  • Yang ST, Wang X, Jia G, Gu Y, Wang T, Nie H, Ge C, Wang H, Liu Y (2008b) Long-term accumulation and low toxicity of single-walled carbon nanotubes in intravenously exposed mice. Toxicol Lett 181:182–189

    PubMed  CAS  Google Scholar 

  • Ye SF, Wu YH, Hou ZQ, Zhang QQ (2009) ROS and NF-kappaB are involved in upregulation of IL-8 in A549 cells exposed to multi-walled carbon nanotubes. Biochem Biophys Res Commun 379:643–648

    PubMed  CAS  Google Scholar 

  • Zeni O, Palumbo R, Bernini R, Zeni L, Sarti M, Scarfi MR (2008) Cytotoxicity investigation on cultured human blood cells treated with single-wall carbon nanotubes. Sensors 8:488–499

    CAS  PubMed Central  Google Scholar 

Download references

Acknowledgments

This publication was supported by the EU 7th Framework Programme under Grant Agreements No. 263147 (NanoValid) and the Danish Centre for Nanosafety (20110092173/3) from the Danish Working Research Fund.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Møller.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 59 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Møller, P., Christophersen, D.V., Jensen, D.M. et al. Role of oxidative stress in carbon nanotube-generated health effects. Arch Toxicol 88, 1939–1964 (2014). https://doi.org/10.1007/s00204-014-1356-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-014-1356-x

Keywords

Navigation