Genotoxicity evaluation of nanosized titanium dioxide, synthetic amorphous silica and multi-walled carbon nanotubes in human lymphocytes

Toxicology in Vitro

Volumn 28, Issue 1, 2014, Pages 60-69

  Tavares, Ana M ^a   Louro, Henriqueta ^a   Antunes, Susana ^a   Quarré, Stephanie ^b   Simar, Sophie ^b   De Temmerman, Pieter Jan ^c   Verleysen, Eveline ^c   Mast, Jan ^c   Jensen, Keld A ^d   Norppa, Hannu ^e   Nesslany, Fabrice ^b   Silva, Maria João ^a  

^a NATIONAL INSTITUTE OF HEALTH DR RICARDO JORGE   (Portugal)

^b INSTITUT PASTEUR DE LILLE   (France)

^c VETERINARY AND AGROCHEMICAL RESEARCH CENTRE   (Belgium)

^d NATIONAL RESEARCH CENTRE FOR THE WORKING ENVIRONMENT   (Denmark)

^e FINNISH INSTITUTE OF OCCUPATIONAL HEALTH   (Finland)

Author keywords

Micronucleus assay; Morphology and size; Multiwalled carbon nanotubes; Primary human lymphocytes; Synthetic amorphous silica nanomaterials; Titanium dioxide nanomaterials

Indexed keywords

MULTI WALLED NANOTUBE; NANOPARTICLE; SILICON DIOXIDE; TITANIUM DIOXIDE;

ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DYNAMIC LIGHT SCATTERING; GENOTOXICITY; HUMAN; HUMAN CELL; HYDRODYNAMICS; LIGHT SCATTERING; LYMPHOCYTE; MICRONUCLEUS; PARTICLE SIZE; SAFETY; TRANSMISSION ELECTRON MICROSCOPY;

MICRONUCLEUS ASSAY; MORPHOLOGY AND SIZE; MULTIWALLED CARBON NANOTUBES; PRIMARY HUMAN LYMPHOCYTES; SYNTHETIC AMORPHOUS SILICA NANOMATERIALS; TITANIUM DIOXIDE NANOMATERIALS;

ADULT; FEMALE; HUMANS; LIGHT; LYMPHOCYTES; MALE; MICRONUCLEUS TESTS; MICROSCOPY, ELECTRON, TRANSMISSION; MUTAGENICITY TESTS; NANOSTRUCTURES; NANOTUBES, CARBON; PARTICLE SIZE; SCATTERING, RADIATION; SILICON DIOXIDE; TITANIUM;

EID: 84888287360     PISSN: 08872333     EISSN: 18793177     Source Type: Journal    
DOI: 10.1016/j.tiv.2013.06.009     Document Type: Article

References (64)

1. Asakura M., Sasaki T., Sugiyama T., Takaya M., Koda S., Nagano K., Arito H., Fukushima S. Genotoxicity and cytotoxicity of multi-wall carbon nanotubes in cultured Chinese hamster lung cells in comparison with chrysotile A fibers. J Occup. Health 2010, 52:155-166.
2. Catalán J., Järventaus H., Vippola M., Savolainen K., Norppa H. Induction of chromosomal aberrations by carbon nanotubes and titanium dioxide nanoparticles in human lymphocytes in vitro. Nanotoxicology 2012, 6:825-836.
3. Corradi S., Gonzalez L., Thomassen L.C., Bilaničová D., Birkedal R.K., Pojana G., Marcomini A., Jensen K.A., Leyns L., Kirsch-Volders M. Influence of serum on in situ proliferation and genotoxicity in A549 human lung cells exposed to nanomaterials. Mutat. Res. 2012, 745:21-27.
4. Cveticanin J., Joksic G., Leskovac A., Petrovic S., Sobot A.V., Neskovic O. Using carbon nanotubes to induce micronuclei and double strand breaks of the DNA in human cells. Nanotechnology 2010, 21:015102.
5. De Temmerman P.-J., Van Doren E., Verleysen E., Van der Stede Y., Francisco M.A.D., Mast J. Quantitative characterization of agglomerates and aggregates of pyrogenic and precipitated amorphous silica nanomaterials by transmission electron microscopy. J. Nanobiotechnology 2012, 10(24).
6. Di Giorgio M.L., Di Bucchianico S., Ragnelli A.M., Aimola P., Santucci S., Poma A. Effects of single and multiwalled carbon nanotubes on macrophages: cyto and genotoxicity and electron microscopy. Mutat. Res. 2011, 722:20-31.
7. Downs T.R., Crosby M.E., Hu T., Kumar S., Sullivan A., Sarlo K., Reeder B., Lynch M., Wagner M., Mills T., Pfuhler S. Silica nanoparticles administered at the maximum tolerated dose induce genotoxic effects through an inflammatory reaction while gold nanoparticles do not. Mutat. Res. 2012, 745(1-2):38-50.
8. EC-European Commission, 2012. COMMISSION RECOMMENDATION of 18 October 2011 on the definition of nanomaterial. <>. http://www.eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:275:0038:0040:EN:PDF.
9. Ema M., Imamura T., Suzuki H., Kobayashi N., Naya M., Nakanishi J. Evaluation of genotoxicity of multi-walled carbon nanotubes in a battery of in vitro and in vivo assays. Regul. Toxicol. Pharmacol. 2012, 63:188-195.
10. 2. Hum. Exp. Toxicol. 2009, 28:339-352.
11. Ghosh M., Bandyopadhyay M., Mukherjee A. Genotoxicity of titanium dioxide (TiO2) nanoparticles at two trophic levels: Plant and human lymphocytes. Chemosphere 2010, 81:1253-1262.
12. Ghosh M., Chakraborty A., Bandyopadhyay M., Mukherjee A. Multi-walled carbon nanotubes (MWCNT): Induction of DNA damage in plant and mammalian cells. J. Hazard. Mater. 2011, 197:327-336.
13. Gonzalez L., Thomassen L.C.J., Plas G., Rabolli V., Napierska D., Decordier I., Roelants M., Hoet P.H., Kirschhock C.E.A., Martens J.A., Lison D., Kirsch-Volders M. Exploring the aneugenic and clastogenic potential in the nanosize range: A549 human lung carcinoma cells and amorphous monodisperse silica nanoparticles as models. Nanotoxicology 2010, 4:382-395.
14. Gonzalez L., Sanderson B.J.S., Kirsch-Volders M. Adaptations of the in vitro MN assay for the genotoxicity assessment of nanomaterials. Mutagenesis 2011, 26:185-191.
15. Gopalan R., Osman I., Amani A., De Matas M., Anderson A. The effect of zinc oxide and titanium dioxide nanoparticles in the Comet assay with UVA photoactivation of human sperm and lymphocytes. Nanotoxicology 2009, 3:33-39.
16. Guidi P., Nigro M., Bernardeschi M., Scarcelli V., Lucchesi P., Onida B., Mortera R., Frenzilli G. Genotoxicity of amorphous silica particles with different structure and dimension in human and murine cell lines. Mutagenesis 2013, 28:171-180.
17. Guo Y.Y., Zhang J., Zheng Y.F., Yang J., Zhu X.Q. Cytotoxic and genotoxic effects of multi-wall carbon nanotubes on human umbilical vein endothelial cells in vitro. Mutat. Res. 2011, 721:184-191.
18. Gurr J.R., Wang A.S., Chen C.H., Jan K.Y. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology 2005, 213:66-73.
19. Hackenberg S., Friehs G., Kessler M., Froelich K., Ginzkey C., Koehler C., Scherzed A., Burghartz M., Kleinsasser N. Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ. Mol. Mutagen. 2011, 52:264-268.
20. Hackenberg S., Scherzed A., Technau A., Kessler M., Froelich K., Ginzkey C., Koehler C., Burghartz M., Hagen R., Kleinsasser N. Cytotoxic, genotoxic and pro-inflammatory effects of zinc oxide nanoparticles in human nasal mucosa cells in vitro. Toxicol. in Vitro. 2011, 25:657-663.
21. Haniu H., Saito N., Matsuda Y., Kim Y.-A., Park K.-C., Tsukahara T., Usui Y., Aoki K., Shimizu M., Ogihara N., Hara K., Takanashi S., Okamoto M., Ishigaki N., Nakamura K., Kato H. Effect of dispersants of multi-walled carbon nanotubes on cellular uptake and biological responses. Int. J. Nanomed. 2011, 6:3295-3307.
22. ISO Particle size analysis - Image analysis methods - Part 1: Static image analysis methods, in ISO 13322-1:2004 2004, International Organization for Standardization, Geneva.
23. ISO Representation of results of particle size analysis - Part 6: Descriptive and quantitative representation of particle shape and morphology, in ISO 9276-6:2008 2008, International Organization for Standardization, Geneva.
24. Jensen, K.A., Kembouche, Y., Christiansen, E., Jacobsen, N.R., Wallin, H., Guiot, C., Spalla, O., Witschger, O., 2011. The generic NANOGENOTOX dispersion protocol - Standard Operation Procedure (SOP). NANOGENOTOX Deliverable Report No. 3: June 2011. <>. http://www.nanogenotox.eu.
25. Jin Y., Kannan S., Wu M., Zhao J.X. Toxicity of luminescent silica nanoparticles to living cells. Chem. Res. Toxicol. 2007, 20:1126-1133.
26. Joint Research Center (JCR), 2011. Impact of Engineered Nanomaterials on Health: Considerations for Benefit-Risk Assessment - EASAC Policy Report - Joint Research Centre Reference Report. Brussels: European Union. <>. http://www.publications.jrc.ec.europa.eu/repository/bitstream/111111111/22610/1/impact%20of%20engineered%20nanomaterials%20on%20health.pdf.
27. Kang S.J., Kim B.M., Lee Y.J., Chung H.W. Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes. Environ. Mol. Mutagen. 2008, 49:399-405.
28. 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. Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay systems. Nanotoxicology 2012, 7(4):452-461.
29. Kim J.S., Lee K., Lee Y.H., Cho H.S., Kim K.H., Choi K.H., Lee S.H., Song K.S., Kang C.S., Yu I.J. Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes. Arch. Toxicol. 2011, 85:775-786.
30. Krumbein W.C., Sloss L.L. Stratigraphy and Sedimentation 1963, W.H, Freeman and Company, San Francisco.
31. Lankoff A., Wegierek-Ciuk A., Kruszewski M., Lisowska H., Banasik-Nowak A., Rozga-Wijas K., Wojewodzka M., Slomkowski S. Effect of surface modification of silica nanoparticles on toxicity and cellular uptake by human peripheral blood lymphocytes in vitro. Nanotoxicology 2012, 10.3109/17435390.2011.649796.
32. Lindberg H.K., Falck G.C., Suhonen S., Vippola M., Vanhala E., Catalán J., Savolainen K., Norppa H. Genotoxicity of nanomaterials: DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibres in human bronchial epithelial cells in vitro. Toxicol. Lett. 2009, 186:166-173.
33. 2 in mice. Mutat. Res. 2012, 745:58-64.
34. Lindberg H.K., Falck G.C.-M., Järventaus H., Suhonen S., Vanhala E., Catalán J., Vippola M., Savolainen K.M., Norppa H. Genotoxicity of single-wall and multi-wall carbon nanotubes in human epithelial and mesothelial cells in vitro. Toxicology 2013, 10.1016/j.tox.2012.12.008.
35. Malhi, G.S., 2012. The Chronic Toxicity of Titanium Dioxide Nanoparticles to the Freshwater Amphipod Hyalella azteca. Department of Biology. Waterloo, Ontario, Wilfrid Laurier University. Master of Science in Integrative Biology.
36. Mast J., Demeestere L. Electron tomography of negatively stained complex viruses: application in their diagnosis. Diag. Pathol. 2009, 4:5.
37. Migliore L., Saracino D., Bonelli A., Colognato R., D'Errico M.R., Magrini A., Bergamaschi A., Bergamaschi E. Carbon nanotubes induce oxidative DNA damage in RAW 264.7 cells. Environ. Mol. Mutagen. 2010, 51:294-303.
38. Muller J., Decordier I., Hoet P.H., Lombaert N., Thomassen L., Huaux F., Lison D., Kirsch-Volders M. Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells. Carcinogenesis 2008, 29:427-433.
39. Mu Q., Hondow N.S., Krzemiński L., Brown A.P., Jeuken L.J., Routledge M.N. Mechanism of cellular uptake of genotoxic silica nanoparticles. Part. Fibre Toxicol. 2012, 23:9-29.
40. Nagai H., Toyokuni S. Differences and similarities between carbon nanotubes and asbestos fibers during mesothelial carcinogenesis: shedding light on fiber entry mechanism. Cancer Sci. 2012, 103:1378-1390.
41. Nagai H., Okazaki Y., Chew S.H., 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. Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis. Proc. Natl Acad. Sci. USA 2011, 108:E1330-1338.
42. Oberdörster G. Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology. J. Int. Med. 2010, 267:89-105.
43. OECD - Organisation for Economic Co-operation and Development, 2010. OECD guideline for the testing of chemicals. In Vitro Mammalian Cell Micronucleus Test. Guideline 487.
44. Oesch F., Landsiedel R. Genotoxicity investigations on nanomaterials. Arch. Toxicol. 2012, 86:985-994.
45. Osman I.F., Baumgartner A., Cemeli E., Fletcher J.N., Anderson D. Genotoxicity and cytotoxicity of zinc oxide and titanium dioxide in HEp-2 cells. Nanomedicine 2010, 5:1193-1203.
46. Park M.V., Verharen H.W., Zwart E., Hernandez L.G., van Benthem J., Elsaesser A., Barnes C., McKerr G., Howard C.V., Salvati A., Lynch I., Dawson K.A., de Jong W.H. Genotoxicity evaluation of amorphous silica nanoparticles of different sizes using the micronucleus and the plasmid lacZ gene mutation assay. Nanotoxicology 2011, 5:168-181.
47. Patlolla A.K., Hussain S.M., Schlager J.J., Patlolla S., Tchounwou P.B. Comparative study of the clastogenicity of functionalized and nonfunctionalized multiwalled carbon nanotubes in bone marrow cells of Swiss-Webster mice. Environ. Toxicol. 2010, 25:608-621.
48. Rahman Q., Lohani M., Dopp E., Pemsel H., Jonas L., Weiss D.G., Schiffmann D. Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. Environ. Health Perspect. 2002, 110:797-800.
49. Sakamoto Y., Nakae D., Fukumori N., Tayama K., Maekawa A., Imai K., Hirose A., Nishimura T., Ohashi N., Ogata A. Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats. J. Toxicol. Sci. 2009, 34:65-76.
50. Shukla R.K., Sharma V., Pandey A.K., Singh S., Sultana S., Dhawan A. ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells. Toxicol. in Vitro 2011, 25:231-241.
51. Silva M.J., Carothers A., Dias A., Luis J.H., Piper J., Boavida M.G. Dose-dependence of radiation-induced micronuclei in cytokinesis-blocked human lymphocytes. Mutat. Res. 1994, 322:117-128.
52. Singh N., Manshian B., Jenkins G.J., Griffiths S.M., Williams P.M., Maffeis T.G., Wright C.J., Doak S.H. NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 2009, 30:3891-3914.
53. Singh, C., Friedrichs, S., Levin, M., Birkedal, R., Jensen, K.A., Pojana, G., Wohlleben, W., Schulte, S., Wiench, K., Turney, T., Koulaeva, O., Marshall, D., Hund-Rinke, K., Kördel, W., Van Doren, E., De Temmerman, P-J., Francisco, M., Mast, J., Gibson, J., Koeber, N.R., Linsinger, T., Klein, C.L., 2011. NM-Series of Representative Manufactured Nanomaterials: Zinc Oxide NM-110, NM-111, NM-112, NM-113 Characterisation and Test Item Preparation. EUR 25066 EN - 2011.
54. Sycheva L.P., Zhurkov V.S., Iurchenko V.V., Daugel-Dauge N.O., Kovalenko M.A., Krivtsova E.K., Durnev A.D. Investigation of genotoxic and cytotoxic effects of micro- and nanosized titanium dioxide in six organs of mice in vivo. Mutat. Res. 2011, 726:8-14.
55. Szendi K., Varga C. Lack of Genotoxicity of Carbon Nanotubes in a Pilot Study. Anticancer Res. 2008, 28:349-352.
56. Takagi A., Hirose A., Nishimura T., Fukumori N., Ogata A., Ohashi N., Kitajima S., Kanno J. Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube. J. Toxicol. Sci. 2008, 33:105-116.
57. Takagi A., Hirose A., Futakuchi M., Tsuda H., Kanno J. Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice. Cancer Sci. 2012, 103:1001-1004.
58. Trouiller B., Reliene R., Westbrook A., Solaimani P., Schiestl R.H. Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer. Res. 2009, 69:8784-8789.
59. Türkez H., Geyikoǧlu F. An in vitro blood culture for evaluating the genotoxicity of titanium dioxide: the responses of antioxidant enzymes. 2007, 23:19-23.
60. Uboldi C., Giudetti G., Broggi F., Gilliland D., Ponti J., Rossi F. Amorphous silica nanoparticles do not induce cytotoxicity, cell transformation or genotoxicity in Balb/3T3 mouse fibroblasts. Mutat. Res. 2012, 745:11-20.
61. Wahab R., Kaushik N.K., Verma A.K., Mishra A., Hwang I.H., Yang Y.B., Shin H.S., Kim Y.S. Fabrication and growth mechanism of ZnO nanostructures and their cytotoxic effect on human brain tumor U87, cervical cancer HeLa, and normal HEK cells. J. Biol. Inorg. Chem. 2011, 16:431-442.
62. 2 particles in cultured human lymphoblastoid cells. Mutat. Res. 2007, 628:99-106.
63. Wijnhoven, S.W.P., Dekkers, S., Hagens, W.I., de Jong, W.H., 2009. Exposure to nanomaterials in consumer products. RIVM Letter, Report 340370001/2009.
64. Zhu L., Chang D.W., Dai L., Hong Y. DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. Nano Lett. 2007, 7:3592-3597.