Skip to main content

Advertisement

Log in

Genotoxic and carcinogenic potential of engineered nanoparticles: an update

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

Abstract

Nanoscience and nanotechnology have seen an exponential growth over the past decade largely due to the unique properties of engineered nanoparticles (ENPs), advances in ENP synthesis, and imaging or analysis tools. The unique properties such as high surface area to volume ratio, abundant reactive sites on the surface, large fraction of atoms located on the exterior face have made these novel materials the most sought after for consumer and industrial applications. This significant increase in the ENP containing consumer products has also enhanced the chances of human and environmental exposure. Humans get exposed to ENPs at various steps of its synthesis (laboratory), manufacture (industry), use (consumer products, devices, medicines, etc.) and through the environment (contaminated water, aerosolized particles, and disposal). Such exposures to ENPs are known to induce genotoxicity, cytotoxicity, and carcinogenicity in biological system. This is attributed to several factors, such as direct interaction of ENPs with the genetic material, indirect damage due to reactive oxygen species generation, release of toxic ions from soluble ENPs, interaction with cytoplasmic/nuclear proteins, binding with mitotic spindle or its components, increased oxidative stress, disturbance of cell cycle checkpoint functions, inhibition of antioxidant defense, and many others. The present review describes an overview of in vitro and in vivo genotoxicity studies with ENPs, advantages and potential problems associated with the methods used in genotoxicity assessment, and the need for appropriate method and approach for risk assessment of ENPs.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ahamed M, Karns M, Goodson M, Rowe J, Hussain SM, Schlager JJ, Hong Y (2008) DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. Toxicol Appl Pharmacol 233:404–410

    CAS  PubMed  Google Scholar 

  • Aitken RJ, Koopman P, Lewis SE (2004) Seeds of concern. Nature 432:48–52

    CAS  PubMed  Google Scholar 

  • Aitken RJ, Hankin SM, Tran CL, Donaldson K, Stone V, Cumpson P, Johnstone J, Chaudhry Q, Cash S, Garrod J (2008) A multidisciplinary approach to the identification of reference materials for engineered nanoparticle toxicology. Nanotoxicology 2:71–78

    CAS  Google Scholar 

  • Ames BN, McCann J, Yamasaki E (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res 31:347–364

    CAS  PubMed  Google Scholar 

  • An H, Liu Q, Ji Q, Jin B (2010) DNA binding and aggregation by carbon nanoparticles. Biochem Biophys Res Commun 393:571–576

    CAS  PubMed  Google Scholar 

  • Asare N, Instanes C, Sandberg WJ, Refsnes M, Schwarze P, Kruszewski M, Brunborg G (2012) Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicology 291:65–72

    CAS  PubMed  Google Scholar 

  • Asha Rani PV, Mun GLK, Hande MP, Valiyaveettil S (2009) Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano 3:279–290

    CAS  Google Scholar 

  • Auffan M, Decome L, Rose J, Orsiere T, De Meo M, Briois V, Chaneac C, Olivi L, Berge-Lefranc JL, Botta A, Wiesner MR, Bottero JY (2006) In vitro interactions between DMSA-coated maghemite nanoparticles and human fibroblasts: a physicochemical and cyto-genotoxical study. Environ Sci Technol 40:4367–4373

    CAS  PubMed  Google Scholar 

  • Auffan M, Rose J, Wiesner MR, Bottero JY (2009) Chemical stability of metallic nanoparticles: a parameter controlling their potential cellular toxicity in vitro. Environ Pollut 157:1127–1133

    CAS  PubMed  Google Scholar 

  • Bajpayee M, Kumar A, Dhawan A (2013) The comet assay: assessment of in vitro and in vivo DNA damage. Methods Mol Biol 1044:325–345

    PubMed  Google Scholar 

  • Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Reiss Y, Shiloh Y, Ziv Y (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281:1674–1677

    CAS  PubMed  Google Scholar 

  • Barchowsky A, O’Hara KA (2003) Metal-induced cell signaling and gene activation in lung diseases. Free Radic Biol Med 34:1130–1135

    CAS  PubMed  Google Scholar 

  • Barnes CA, Elsaesser A, Arkusz J, Smok A, Palus J, Lesniak A, Salvati A, Hanrahan JP, Jong WH, Dziubaltowska E, Stepnik M, Rydzynski K, McKerr G, Lynch I, Dawson KA, Howard CV (2008) Reproducible comet assay of amorphous silica nanoparticles detects no genotoxicity. Nano Lett 8:3069–3074

    CAS  PubMed  Google Scholar 

  • Baweja L, Gurbani D, Shanker R, Pandey AK, Subramanian V, Dhawan A (2011) C60-fullerene binds with the ATP binding domain of human DNA topoiosmerase II alpha. J Biomed Nanotechnol 7:177–178

    CAS  PubMed  Google Scholar 

  • Bergamaschi E, Bussolati O, Magrini A, Bottini M, Migliore L, Bellucci S, Iavicoli I, Bergamaschi A (2006) Nanomaterials and lung toxicity: interactions with airways cells and relevance for occupational health risk assessment. Int J Immunopathol Pharmacol 19:3–10

    CAS  PubMed  Google Scholar 

  • Bhattacharya K, Davoren M, Boertz J, Schins RP, Hoffmann E, Dopp E (2009) Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells. Part Fibre Toxicol 6:17

    PubMed  Google Scholar 

  • Borm PJA, Berube D (2008) A tale of opportunities, uncertainties and risks. Nano Today 3:56–59

    CAS  Google Scholar 

  • Borm PJ, Kreyling W (2004) Toxicological hazards of inhaled nanoparticles-potential implications for drug delivery. J Nanosci Nanotechnol 4:521–531

    CAS  PubMed  Google Scholar 

  • Borm PJ, Robbins D, Haubold S, Kuhlbusch T, Fissan H, Donaldson K, Schins R, Stone V, Kreyling W, Lademann J, Krutmann J, Warheit D, Oberdorster E (2006) The potential risks of nanomaterials: a review carried out for ECETOC. Part Fibre Toxicol 3:11

    PubMed  Google Scholar 

  • Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230

    CAS  PubMed  Google Scholar 

  • Collins A, Dusinska M, Gedik C, Stetina R (1996) Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect 104:465–469

    CAS  PubMed  Google Scholar 

  • Comet Assay Forum (2013). http://www.cometassayindia.org/

  • Das S, Singh S, Dowding JM, Oommen S, Kumar A, Sayle TX, Saraf S, Patra CR, Vlahakis NE, Sayle DC, Self WT, Seal S (2012) The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments. Biomaterials 33:7746–7755

    CAS  PubMed  Google Scholar 

  • Dhawan A, Sharma V (2010) Toxicity assessment of nanomaterials: methods and challanges. Anal Bioanal Chem 398:589–605

    CAS  PubMed  Google Scholar 

  • Dhawan A, Taurozzi JS, Pandey AK, Shan W, Miller SM, Hashsham SA, Tarabara VV (2006) Stable colloidal dispersions of C60 fullerenes in water: evidence for genotoxicity. Environ Sci Technol 40:7394–7401

    CAS  PubMed  Google Scholar 

  • Dhawan A, Sharma V, Parmar D (2009) Nanomaterials: a challenge for toxicologists. Nanotoxicology 3:1–9

    CAS  Google Scholar 

  • Di Sotto A, Chiaretti M, Carru GA, Bellucci S, Mazzanti G (2009) Multi-walled carbon nanotubes: lack of mutagenic activity in the bacterial reverse mutation assay. Toxicol Lett 184:192–197

    PubMed  Google Scholar 

  • Di Virgilio AL, Reigosa M, Arnal PM, Fernandez Lorenzo de Mele M (2010) Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells. J Hazard Mater 177:711–718

    PubMed  Google Scholar 

  • Dufour EK, Kumaravel T, Nohynek GJ, Kirkland D, Toutain H (2006) Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells. Mutat Res Genetic Toxicol Environ Mutagen 607:215–224

    CAS  Google Scholar 

  • Dusinska M, Collins A (1996) Detection of oxidised purines and UV-induced photoproducts in DNA, by inclusion of lesion-specific enzymes in the comet assay (single cell gel electrophoresis). ATLA 24:405–411

    Google Scholar 

  • Dusinska M, Fjellsbo L, Magdolenova Z, Rinna A, Runden Pran E, Bartonova A, Heimstad E, Harju M, Tran L, Ross B, Juillerat L, Halamoda Kenzaui B, Marano F, Boland S, Guadaginini R, Saunders M, Cartwright L, Carreira S, Whelan M, Kelin C, Worth A, Palosaari T, Burello E, Housiadas C, Pilou M, Volkovova K, Tulinska J, Kazimirova A, Barancokova M, Sebekova K, Hurbankova M, Kovacikova Z, Knudsen L, Poulsen M, Mose T, Vila M, Gombau L, Fernandez B, Castell J, Marcomini A, Pojana G, Bilanicova D, Vallotto D (2009) Testing strategies for the safety of nanoparticles used in medical applications. Nanomedicine (London, England) 4:605–607

  • Elsaesser A, Howard CV (2011) Toxicology of nanoparticles. Adv Drug Deliv Rev 64:129–137

    PubMed  Google Scholar 

  • Eom HJ, Choi J (2010) p38 MAPK activation, DNA damage, cell cycle arrest and apoptosis as mechanisms of toxicity of silver nanoparticles in Jurkat T cells. Environ Sci Technol 44:8337–8342

    CAS  PubMed  Google Scholar 

  • Falck GC, Lindberg HK, Suhonen S, Vippola M, Vanhala E, Catalan J, Savolainen K, Norppa H (2009) Genotoxic effects of nanosized and fine TiO2. Hum Exp Toxicol 28:339–352

    CAS  PubMed  Google Scholar 

  • Feliu N, Fadeel B (2010) Nanotoxicology: no small matter. Nanoscale 2:2514–2520

    CAS  PubMed  Google Scholar 

  • Finette BA, Kendall H, Vacek PM (2002) Mutational spectral analysis at the HPRT locus in healthy children. Mutat Res 505:27–41

    CAS  PubMed  Google Scholar 

  • Flower NA, Brabu B, Revathy M, Gopalakrishnan C, Raja SV, Murugan SS, Kumaravel TS (2012) Characterization of synthesized silver nanoparticles and assessment of its genotoxicity potentials using the alkaline comet assay. Mutat Res 742:61–65

    CAS  PubMed  Google Scholar 

  • Foldbjerg R, Dang DA, Autrup H (2012) Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Arch Toxicol 85:743–750

    Google Scholar 

  • Folkmann JK, Risom L, Jacobsen NR, Wallin H, Loft S, Maller 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

    CAS  PubMed  Google Scholar 

  • Freitasa MLL, Silvaa LP, Azevedoa RB, Garciaa VAP, Lacavaa LM, Grisóliaa CK, Luccia CM, Moraisb PC, Silvab MFD, Buskec N, Curid R, Lacavaa ZGM (2002) A double-coated magnetite-based magnetic fluid evaluation by cytometry and genetic tests. J Magn Magn Mater 252:396–398

    Google Scholar 

  • Gerloff K, Albrecht C, Boots AW, Förster I, Schins RPF (2009) Cytotoxicity and oxidative DNA damage by nanoparticles in human intestinal Caco-2 cells. Nanotoxicology 3:355–364

    CAS  Google Scholar 

  • Gopalan R, Osman I, Amani A, Matas M, Anderson D (2009) The effect of zinc oxide and titanium dioxide nanoparticles in the Comet assay with UVA photoactivation of human sperm and lymphocytes. Nanotoxicology 3:33–39

    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

    CAS  PubMed  Google Scholar 

  • Gupta SK, Baweja L, Gurbani D, Pandey AK, Dhawan A (2011) Interaction of C60 fullerene with the proteins involved in DNA mismatch repair pathway. J Biomed Nanotechnol 7:179–180

    CAS  PubMed  Google Scholar 

  • Gurr JR, Wang ASS, Chen CH, Jan KY (2005) Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial cells. Toxicology 213:66–73

    CAS  PubMed  Google Scholar 

  • Hackenberg S, Friehs G, Kessler M, Froelich K, Ginzkey C, Koehler C, Scherzed A, Burghartz M, Kleinsasser N (2011a) Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ Mol Mutagen 52:264–268

    CAS  PubMed  Google Scholar 

  • Hackenberg S, Scherzed A, Kessler M, Hummel S, Technau A, Froelich K, Ginzkey C, Koehler C, Hagen R, Kleinsasser N (2011b) Silver nanoparticles: evaluation of DNA damage, toxicity and functional impairment in human mesenchymal stem cells. Toxicol Lett 201:27–33

    CAS  PubMed  Google Scholar 

  • Hackenberg S, Zimmermann FZ, Scherzed A, Friehs G, Froelich K, Ginzkey C, Koehler C, Burghartz M, Hagen R, Kleinsasser N (2011c) Repetitive exposure to zinc oxide nanoparticles induces DNA damage in human nasal mucosa mini organ cultures. Environ Mol Mutagen 52:582–589

    CAS  PubMed  Google Scholar 

  • Hardman R (2006) A toxicological review of quantum dots: toxicity depends on physicochemical and environmental factors. Environ Health Perspect 114:165–172

    PubMed  Google Scholar 

  • Heng BC, Zhao X, Tan EC, Khamis N, Assodani A, Xiong S, Ruedl C, Ng KW, Loo JS (2011a) Evaluation of the cytotoxic and inflammatory potential of differentially shaped zinc oxide nanoparticles. Arch Toxicol 85:1517–1528

    CAS  PubMed  Google Scholar 

  • Heng BC, Zhao X, Xiong S, Ng KW, Boey FY, Loo JS (2011b) Cytotoxicity of zinc oxide (ZnO) nanoparticles is influenced by cell density and culture format. Arch Toxicol 85:695–704

    CAS  PubMed  Google Scholar 

  • Howard AG (2009) On the challenge of quantifying man-made nanoparticles in the aquatic environment. J Environ Monit 12:135–142

    PubMed  Google Scholar 

  • Huang CC, Chen CT, Shiang YC, Lin ZH, Chang HT (2009) Synthesis of fluorescent carbohydrate-protected Au nanodots for detection of Concanavalin A and Escherichia coli. Anal Chem 81:875–882

    CAS  PubMed  Google Scholar 

  • Hudecova A, Kusznierewicz B, Runden-Pran E, Magdolenova Z, Hasplova K, Rinna A, Fjellsbo LM, Kruszewski M, Lankoff A, Sandberg WJ, Refsnes M, Skuland T, Schwarze P, Brunborg G, Bjoras M, Collins A, Miadokova E, Galova E, Dusinska M (2012) Silver nanoparticles induce premutagenic DNA oxidation that can be prevented by phytochemicals from Gentiana asclepiadea. Mutagenesis 27:759–769

    CAS  PubMed  Google Scholar 

  • Ismail IH, Wadhra TI, Hammarsten O (2007) An optimized method for detecting gamma-H2AX in blood cells reveals a significant interindividual variation in the gamma-H2AX response among humans. Nucleic Acids Res 35:e36

    PubMed  Google Scholar 

  • Jacobsen NR, Maller P, Jensen KA, Vogel U, Ladefoged O, Loft S, Wallin H (2009) Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/-mice. Part Fibre Toxicol 6:17

    Google Scholar 

  • Jin P, Chen Y, Zhang SB, Chen Z (2012) Interactions between Al(1)(2)X (X = Al, C, N and P) nanoparticles and DNA nucleobases/base pairs: implications for nanotoxicity. J Mol Model 18:559–568

    CAS  PubMed  Google Scholar 

  • Jugan ML, Barillet S, Simon-Deckers A, Herlin-Boime N, Sauvaigo S, Douki T, Carriere M (2012) Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells. Nanotoxicology 6:501–513

    CAS  PubMed  Google Scholar 

  • Kain J, Karlsson HL, Moller L (2012) DNA damage induced by micro- and nanoparticles-interaction with FPG influences the detection of DNA oxidation in the comet assay. Mutagenesis 27:491–500

    CAS  PubMed  Google Scholar 

  • Kang SJ, Kim BM, Lee YJ, Chung HW (2008) Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes. Environ Mol Mutagen 49:399–405

    CAS  PubMed  Google Scholar 

  • Karlsson HL (2010) The comet assay in nanotoxicology research. Anal Bioanal Chem 398:651–666

    CAS  PubMed  Google Scholar 

  • Karlsson HL, Nygren J, Moller L (2004) Genotoxicity of airborne particulate matter: the role of cell-particle interaction and of substances with adduct-forming and oxidizing capacity. Mutat Res 565:1–10

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Karlsson S, Modin J, Becker HC, Hammarstrom L, Grennberg H (2008b) How close can you get? Studies of ultrafast light-induced processes in ruthenium-[60] fullerene dyads with short pyrazolino and pyrrolidino links. Inorg Chem 47:7286–7294

    CAS  PubMed  Google Scholar 

  • Karlsson HL, Gustafsson J, Cronholm P, Moller L (2009) Size-dependent toxicity of metal oxide particles—a comparison between nano- and micrometer size. Toxicol Lett 188:112–118

    CAS  PubMed  Google Scholar 

  • Khalil WK, Girgis E, Emam AN, Mohamed MB, Rao KV (2011) Genotoxicity evaluation of nanomaterials: DNA damage, micronuclei, and 8-hydroxy-2-deoxyguanosine induced by magnetic doped CdSe quantum dots in male mice. Chem Res Toxicol 24:640–650

    CAS  PubMed  Google Scholar 

  • Khan MI, Mohammad A, Patil G, Naqvi SA, Chauhan LK, Ahmad I (2011) Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles. Biomaterials 33:1477–1488

    PubMed  Google Scholar 

  • Kim YS, Kim JS, Cho HS, Rha DS, Kim JM, Park JD, Choi BS, Lim R, Chang HK, Chung YH, Kwon IH, Jeong J, Han BS, Yu IJ (2008) Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague-Dawley rats. Inhalation Toxicol 20:575–583

    CAS  Google Scholar 

  • Kim IS, Baek M, Choi SJ (2010) Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells. J Nanosci Nanotechnol 10:3453–3458

    CAS  PubMed  Google Scholar 

  • Kim HR, Kim MJ, Lee SY, Oh SM, Chung KH (2011) Genotoxic effects of silver nanoparticles stimulated by oxidative stress in human normal bronchial epithelial (BEAS-2B) cells. Mutat Res 726:129–135

    CAS  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 70:2071–2079

    CAS  Google Scholar 

  • Konczol M, Ebeling S, Goldenberg E, Treude F, Gminski R, Giere R, Grobety B, Rothen-Rutishauser B, Merfort I, Mersch-Sundermann V (2011) Cytotoxicity and genotoxicity of size-fractionated iron oxide (magnetite) in A549 human lung epithelial cells: role of ROS, JNK, and NF-kappaB. Chem Res Toxicol 24:1460–1475

    CAS  PubMed  Google Scholar 

  • Kumar A, Pandey AK, Singh SS, Shanker R, Dhawan A (2011a) Cellular response to metal oxide nanoparticles in bacteria. J Biomed Nanotechnol 7:102–103

    PubMed  Google Scholar 

  • Kumar A, Pandey AK, Singh SS, Shanker R, Dhawan A (2011b) Cellular uptake and mutagenic potential of metal oxide nanoparticles in bacterial cells. Chemosphere 83:1124–1132

    CAS  PubMed  Google Scholar 

  • Kumar A, Pandey AK, Singh SS, Shanker R, Dhawan A (2011c) A flow cytometric method to assess nanoparticle uptake in bacteria. Cytometry A 79A:707–712

    CAS  Google Scholar 

  • Kumar A, Pandey AK, Singh SS, Shanker R, Dhawan A (2011d) Engineered ZnO and TiO2 nanoparticles induce oxidative stress and DNA damage leading to reduced viability of Escherichia coli. Free Radical Biol Med 51:1872–1881

    CAS  Google Scholar 

  • Kumar A, Shanker R, Dhawan A (2011e) The need for novel approaches in ecotoxicity of engineered nanomaterials. J Biomed Nanotechnol 7:79–80

    CAS  PubMed  Google Scholar 

  • Kumar A, Pandey AK, Shanker R, Dhawan A (2012) Microorganism: a versatile model for toxicity assessment of engineered nanomaterials. In: Cioffi N, Rai M (eds) Nano-antimicrobials: progress and prospects. Springer, Heidelberg, pp 497–524

    Google Scholar 

  • Kumar A, Sharma V, Dhawan A (2013) Methods for detection of oxidative stress and genotoxicity of engineered nanoparticles. Methods Mol Biol 1028:231–246

    PubMed  Google Scholar 

  • Kumari M, Khan SS, Pakrashi S, Mukherjee A, Chandrasekaran N (2011) Cytogenetic and genotoxic effects of zinc oxide nanoparticles on root cells of Allium cepa. J Hazard Mater 190:613–621

    CAS  PubMed  Google Scholar 

  • Landsiedel R, Fabian E, Ma-Hock L, van Ravenzwaay B, Wohlleben W, Wiench K, Oesch F (2012) Toxico-/biokinetics of nanomaterials. Arch Toxicol 86:1021–1060

    CAS  PubMed  Google Scholar 

  • Lee JC, Son YO, Pratheeshkumar P, Shi X (2012) Oxidative stress and metal carcinogenesis. Free Radical Biol Med 53:742–757

    CAS  Google Scholar 

  • Lewis DJ, Bruce C, Bohic S, Cloetens P, Hammond SP, Arbon D, Blair-Reid S, Pikramenou Z, Kysela B (2010) Intracellular synchrotron nanoimaging and DNA damage/genotoxicity screening of novel lanthanide-coated nanovectors. Nanomedicine (London, England) 5:1547–1557

    Google Scholar 

  • Li CH, Shen CC, Cheng YW, Huang SH, Wu CC, Kao CC, Liao JW, Kang JJ (2011) Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice. Nanotoxicology 6:746–756

    PubMed  Google Scholar 

  • Luo C, Urgard E, Vooder T, Metspalu A (2011) The role of COX-2 and Nrf2/ARE in anti-inflammation and antioxidative stress: aging and anti-aging. Med Hypotheses 77:174–178

    CAS  PubMed  Google Scholar 

  • Maenosono S, Suzuki T, Saita S (2007) Mutagenicity of water-soluble FePt nanoparticles in Ames test. J Toxicol Sci 32:575–579

    CAS  PubMed  Google Scholar 

  • Maenosono S, Yoshida R, Saita S (2009) Evaluation of genotoxicity of amine-terminated water-dispersible FePt nanoparticles in the Ames test and in vitro chromosomal aberration test. J Toxicol Sci 34:349–354

    CAS  PubMed  Google Scholar 

  • Magdolenova Z, Collins A, Kumar A, Dhawan A, Stone V, Dusinska M (2013) Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology. doi:10.3109/17435390.17432013.17773464

  • Mates JM, Segura JA, Alonso FJ, Marquez J (2012) Oxidative stress in apoptosis and cancer: an update. Arch Toxicol 86:1649–1665

    CAS  PubMed  Google Scholar 

  • Maynard AD (2007) Nanotechnology: the next big thing, or much ado about nothing? Ann Occup Hyg 51:1–12

    CAS  PubMed  Google Scholar 

  • Midander K, Cronholm P, Karlsson HL, Elihn K, Moller L, Leygraf C, Wallinder IO (2009) Surface characteristics, copper release, and toxicity of nano- and micrometer-sized copper and copper(II) oxide particles: a cross-disciplinary study. Small 5:389–399

    CAS  PubMed  Google Scholar 

  • Mortelmans K, Zeiger E (2000) The Ames Salmonella/microsome mutagenicity assay. Mutat Res 455:29–60

    CAS  PubMed  Google Scholar 

  • Mrdanović J, Solajić S, Bogdanović V, Stankov K, Bogdanović G, Djordjevic A (2009) Effects of fullerenol C60(OH)24 on the frequency of micronuclei and chromosome aberrations in CHO-K1 cells. Mutat Res 680:25–30

    PubMed  Google Scholar 

  • Muller J, Decordier I, Hoet PH, Lombaert N, Thomassen L, Huaux F, Lison D, Kirsch-Volders M (2008) Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells. Carcinogenesis 29:427–433

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Navarro E, Baun A, Behra R, Hartmann NB, Filser J, Miao AJ, Quigg A, Santschi PH, Sigg L (2008) Environmental behavior and ecotoxicity of engineered nanoparticles to algae, plants, and fungi. Ecotoxicology (London, England) 17:372–386

  • Ng CT, Li JJ, Bay BH, Yung LY (2010) Current studies into the genotoxic effects of nanomaterials. J Nucleic Acids 2010:1–12

  • Nowack B, Bucheli TD (2007) Occurrence, behavior and effects of nanoparticles in the environment. Environ Pollut 150:5–22

    CAS  PubMed  Google Scholar 

  • Oberdarster G, Oberdarster E, Oberdarster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839

    Google Scholar 

  • Oberley TD (2002) Oxidative damage and cancer. Am J Pathol 160:403–408

    CAS  PubMed  Google Scholar 

  • Osman IF, Baumgartner A, Cemeli E, Fletcher JN, Anderson D (2010) Genotoxicity and cytotoxicity of zinc oxide and titanium dioxide in HEp-2 cells. Nanomedicine 5:1193–1203

    CAS  PubMed  Google Scholar 

  • PEN (2013) Project of the emerging nanotechnologies (PEN). Available at PEN http://www.nanotechproject.org/inventories/consumer/browse/products/

  • Petkovic J, Zegura B, Stevanovic M, Drnovsek N, Uskokovic D, Novak S, Filipic M (2011) DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells. Nanotoxicology 5:341–353

    CAS  PubMed  Google Scholar 

  • Pierscionek BK, Li Y, Yasseen AA, Colhoun LM, Schachar RA, Chen W (2010) Nanoceria have no genotoxic effect on human lens epithelial cells. Nanotechnology 21:035102

    PubMed  Google Scholar 

  • Pulido MD, Parrish AR (2003) Metal-induced apoptosis: mechanisms. Mutat Res 533:227–241

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Rehn B, Seiler F, Rehn S, Bruch J, Maier M (2003) Investigations on the inflammatory and genotoxic lung effects of two types of titanium dioxide: untreated and surface treated. Toxicol Appl Pharmacol 189:84–95

    CAS  PubMed  Google Scholar 

  • Roco MC (2005) Environmentally responsible development of nanotechnology. Environ Sci Technol 39:106A–112A

    CAS  PubMed  Google Scholar 

  • Rothen-Rutishauser B, Grass RN, Blank F, Limbach LK, Muhlfeld C, Brandenberger C, Raemy DO, Gehr P, Stark WJ (2009) Direct combination of nanoparticle fabrication and exposure to lung cell cultures in a closed setup as a method to simulate accidental nanoparticle exposure of humans. Environ Sci Technol 43:2634–2640

    CAS  PubMed  Google Scholar 

  • Royal Society and the Royal Academy of Engineers: Nanoscience and nanotechnologies: opportunities and uncertainties (2004)

  • Sadeghiani N, Barbosa L, Silva L, Azevedo R, Morais P, Lacava Z (2005) Genotoxicity and inflammatory investigation in mice treated with magnetite nanoparticles surface coated with polyaspartic acid. J Magn Magn Mater 289:466–468

    CAS  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

    CAS  PubMed  Google Scholar 

  • Sayes CM, Reed KL, Glover KP, Swain KA, Ostraat ML, Donner EM, Warheit DB (2010) Changing the dose metric for inhalation toxicity studies: short-term study in rats with engineered aerosolized amorphous silica nanoparticles. Inhalation Toxicol 22:348–354

    CAS  Google Scholar 

  • Schulz M, Ma-Hock L, Brill S, Strauss V, Treumann S, Groters S, van Ravenzwaay B, Landsiedel R (2012) Investigation on the genotoxicity of different sizes of gold nanoparticles administered to the lungs of rats. Mutat Res 745:51–57

    CAS  PubMed  Google Scholar 

  • Science Daily (2013). http://www.sciencedaily.com/articles/n/nanoparticle.htm. 1 July 2013

  • Sera N, Tokiwa H, Miyata N (1996) Mutagenicity of the fullerene C60-generated singlet oxygen dependent formation of lipid peroxides. Carcinogenesis 17:2163–2169

    CAS  PubMed  Google Scholar 

  • Sharma V, Shukla RK, Saxena N, Parmar D, Das M, Dhawan A (2009) DNA damaging potential of zinc oxide nanoparticles in human epidermal cells. Toxicol Lett 185:211–218

    CAS  PubMed  Google Scholar 

  • Sharma V, Anderson D, Dhawan A (2011a) Zinc oxide nanoparticles induce oxidative stress and genotoxicity in human liver cells (HepG2). J Biomed Nanotechnol 7:98–99

    CAS  PubMed  Google Scholar 

  • Sharma V, Singh SK, Anderson D, Tobin DJ, Dhawan A (2011b) Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes. J Nanosci Nanotechnol 11:3782–3788

    CAS  PubMed  Google Scholar 

  • Sharma V, Anderson D, Dhawan A (2012a) Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis 17:852–870

    CAS  PubMed  Google Scholar 

  • Sharma V, Kumar A, Dhawan A (2012b) Nanomaterials: exposure, effects and toxicity assessment. Proc Natl Acad Sci India Sect B Biol Sci 82:3–11

    CAS  Google Scholar 

  • Sharma V, Singh P, Pandey AK, Dhawan A (2012c) Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutat Res 745:84–91

    CAS  PubMed  Google Scholar 

  • Shinohara N, Matsumoto K, Endoh S, Maru J, Nakanishi J (2009) In vitro and in vivo genotoxicity tests on fullerene C60 nanoparticles. Toxicol Lett 191:289–296

    CAS  PubMed  Google Scholar 

  • Shukla RK, Kumar A, Pandey AK, Singh SS, Dhawan A (2011a) Titanium dioxide nanoparticles induce oxidative stress-mediated apoptosis in human keratinocyte cells. J Biomed Nanotechnol 7:100–101

    CAS  PubMed  Google Scholar 

  • Shukla RK, Sharma V, Pandey AK, Singh S, Sultana S, Dhawan A (2011b) ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells. Toxicol In Vitro 25:231–241

    CAS  PubMed  Google Scholar 

  • Shukla RK, Kumar A, Gurbani D, Pandey AK, Singh S, Dhawan A (2013) TiO(2) nanoparticles induce oxidative DNA damage and apoptosis in human liver cells. Nanotoxicology 7:48–60

    CAS  PubMed  Google Scholar 

  • Singh S (2013) Nanomaterials as non-viral siRNA delivery agents for cancer therapy. Bioimpacts 3:53–65

    CAS  PubMed  Google Scholar 

  • Singh N, Manshian B, Jenkins GJS, Griffiths SM, Williams PM, Maffeis TGG, Wright CJ, Doak SH (2009) Nano-genotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 30:3891–3914

    CAS  PubMed  Google Scholar 

  • Srivastava RK, Rahman Q, Kashyap MP, Lohani M, Pant AB (2011) Ameliorative effects of dimetylthiourea and N-acetylcysteine on nanoparticles induced cyto-genotoxicity in human lung cancer cells-A549. PLoS ONE 6:e25767

    CAS  PubMed  Google Scholar 

  • Stone V, Donaldson K (2006) Nanotoxicology: signs of stress. Nat Nanotechnol 1:23–24

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Szendi K, Varga C (2008) Lack of genotoxicity of carbon nanotubes in a pilot study. Anticancer Res 28:349–352

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Theogaraj E, Riley S, Hughes L, Maier M, Kirkland D (2007) An investigation of the photo-clastogenic potential of ultrafine titanium dioxide particles. Mutat Res 634:205–219

    CAS  PubMed  Google Scholar 

  • Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH (2009) Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res 69:8784–8789

    CAS  PubMed  Google Scholar 

  • Tsaousi A, Jones E, Case CP (2010) The in vitro genotoxicity of orthopaedic ceramic (Al2O3) and metal (CoCr alloy) particles. Mutat Res 697:1–9

    CAS  PubMed  Google Scholar 

  • Turkez H, Geyikoglu F (2007) An in vitro blood culture for evaluating the genotoxicity of titanium dioxide: the responses of antioxidant enzymes. Toxicol Ind Health 23:19–23

    CAS  PubMed  Google Scholar 

  • USNTC (2004) USNTC (U.S. National Science and Technology Council). The National Nanotechnology Initiative: Strategic plan. Available at http://www.nano.gov/NNI_Strategic_Plan_2004.pdf (verified 4 Aug. 2010). Nanoscale Science, Engineering, and Technology Subcommittee, Nat. Technol. Coord. Office, Arlington, VA

  • Valko M, Morris H, Cronin MT (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–1208

    CAS  PubMed  Google Scholar 

  • Vallabani NV, Mittal S, Shukla RK, Pandey AK, Dhakate SR, Pasricha R, Dhawan A (2011) Toxicity of graphene in normal human lung cells (BEAS-2B). J Biomed Nanotechnol 7:106–107

    CAS  PubMed  Google Scholar 

  • Vevers WF, Jha AN (2008) Genotoxic and cytotoxic potential of titanium dioxide (TiO2) nanoparticles on fish cells in vitro. Ecotoxicology (London, England) 17:410–420

    Google Scholar 

  • Wang JJ, Sanderson BJ, Wang H (2007) Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells. Mutat Res 628:99–106

    CAS  PubMed  Google Scholar 

  • Wang D, Sun L, Liu W, Chang W, Gao X, Wang Z (2009) Photoinduced DNA cleavage by alpha-, beta-, and gamma-cyclodextrin-bicapped C60 supramolecular complexes. Environ Sci Technol 43:5825–5829

    CAS  PubMed  Google Scholar 

  • Wang S, Hunter L, Arslan Z, Wilkerson M, Wickliffe J (2011) Chronic exposure to nanosized anatase titanium dioxide is not cyto or genotoxic to Chinese hamster ovary cells. Environ Mol Mutagen 52:614–622

    CAS  PubMed  Google Scholar 

  • Warheit DB, Hoke RA, Finlay C, Donner EM, Reed KL, Sayes CM (2007) Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management. Toxicol Lett 171:99–110

    CAS  PubMed  Google Scholar 

  • Wirnitzer U, Herbold B, Voetz M, Ragot J (2009) Studies on the in vitro genotoxicity of baytubes, agglomerates of engineered multi-walled carbon-nanotubes (MWCNT). Toxicol Lett 186:160–165

    CAS  PubMed  Google Scholar 

  • Wise JP Sr, Goodale BC, Wise SS, Craig GA, Pongan AF, Walter RB, Thompson WD, Ng AK, Aboueissa AM, Mitani H, Spalding MJ, Mason MD (2010) Silver nanospheres are cytotoxic and genotoxic to fish cells. Aquat Toxicol 97:34–41

    CAS  PubMed  Google Scholar 

  • Xie G, Sun J, Zhong G, Shi L, Zhang D (2010) Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Arch Toxicol 84:183–190

    CAS  PubMed  Google Scholar 

  • Xu A, Chai Y, Nohmi T, Hei TK (2009) Genotoxic responses to titanium dioxide nanoparticles and fullerene in gpt delta transgenic MEF cells. Part Fibre Toxicol 6:13

    Google Scholar 

  • Yang H, Liu C, Yang D, Zhang H, Xi Z (2009) 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

    PubMed  Google Scholar 

  • Yoshida R, Kitamura D, Maenosono S (2009) Mutagenicity of water-soluble ZnO nanoparticles in Ames test. J Toxicol Sci 34:119–122

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Funding received from the Council of Scientific and Industrial Research, New Delhi (NanoSHE;BSC-0112); the UK India Education and Research Initiative (UKIERI) standard award to Institute of Life Sciences, Ahmedabad University, India (Grant No. IND/CONT/E/11-12/217) and from the Department of Biotechnology, Government of India under the NewINDIGO Scheme for NanoLINEN project is gratefully acknowledged. Funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 263147 (NanoValid—Development of reference methods for hazard identification, risk assessment and LCA of engineered nanomaterials) is also acknowledged. The financial assistance for the Centre for Nanotechnology Research and Applications (CENTRA) by The Gujarat Institute for Chemical Technology (GICT) is also acknowledged.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ashutosh Kumar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, A., Dhawan, A. Genotoxic and carcinogenic potential of engineered nanoparticles: an update. Arch Toxicol 87, 1883–1900 (2013). https://doi.org/10.1007/s00204-013-1128-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-013-1128-z

Keywords

Navigation