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Orginal Articles

Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles

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Pages 233-278 | Received 23 Dec 2011, Accepted 31 Jan 2013, Published online: 20 Mar 2013

References

  • Ahamed M, Karns M, Goodson M, Rowe J, Hussain SM, Schlager JJ, 2008. DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. Toxicol Appl Pharmacol 233:404–410.
  • An H, Liu Q, Ji Q, Jin B. 2010. DNA binding and aggregation by carbon nanoparticles. Biochem Biophys Res Commun 393:571–576.
  • Aoshima H, Yamana S, Nakamura S, Mashino T. 2010. Biological safety of water-soluble fullerenes evaluated using tests for genotoxicity, phototoxicity, and pro-oxidant activity. J Toxicol Sci 35:401–409.
  • Arora S, Rajwade JM, Paknikar KM. 2012. Nanotoxicology and in vitro studies: the need of the hour. Toxicol Appl Pharmacol 258:151–165.
  • Asare N, Instanes C, Sandberg WJ, Refsnes M, Schwarze P, Kruszewski M, 2012. Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicology 291:65–72.
  • Asharani PV, Low Kah Mun G, Hande MP, Valiyaveettil S. 2009. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano 3:279–290.
  • Asharani PV, Xinyi N, Hande MP, Valiyaveettil S. 2010. DNA damage and p53-mediated growth arrest in human cells treated with platinum nanoparticles. Nanomedicine (Lond) 5:51–64.
  • Auffan M, Decome L, Rose J, Orsiere T, De Meo M, Briois V, 2006. In vitro interactions between DMSA-coated maghemite nanoparticles and human fibroblasts: a physicochemical and cyto-genotoxical study. Environ Sci Technol 40:4367–4373.
  • Balasubramanyam A, Sailaja N, Mahboob M, Rahman MF, Hussain SM, Grover P. 2010. In vitro mutagenicity assessment of aluminium oxide nanomaterials using the Salmonella/microsome assay. Toxicol In Vitro 24:1871–1876.
  • Barillet S, Jugan ML, Laye M, Leconte Y, Herlin-Boime N, Reynaud C, 2010. In vitro evaluation of SiC nanoparticles impact on A549 pulmonary cells: cyto-, genotoxicity and oxidative stress. Toxicol Lett 198:324–330.
  • Barnes CA, Elsaesser A, Arkusz J, Smok A, Palus J, Leśniak A, 2008. Reproducible comet assay of amorphous silica nanoparticles detects no genotoxicity. Nano Lett 8:3069–3074.
  • 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.
  • Bernardeschi M, Guidi P, Scarcelli V, Frenzilli G, Nigro M. 2010. Genotoxic potential of TiO2 on bottlenose dolphin leukocytes. Anal Bioanal Chem 396:619–623.
  • 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.
  • Bonassi S, Norppa H, Ceppi M, Strömberg U, Vermeulen R, Znaor A, 2008. Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries. Carcinogenesis 29:1178–1183.
  • Bourdon JA, Saber AT, Jacobsen NR, Jensen KA, Madsen AM, Lamson JS, 2012. Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver. Part Fibre Toxicol 9:5.
  • Brunner TJ, Wick P, Manser P, Spohn P, Grass RN, Limbach LK. 2006. In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. Environ Sci Technol 40:4374–4381.
  • Calzolai L, Franchini F, Gilliland D, Rossi F. 2010. Protein-nanoparticle interaction: identification of the ubiquitin-gold nanoparticle interaction site. Nano Lett 10:3101–3105.
  • Chan VS. 2006. Nanomedicine: an unresolved regulatory issue. Regul Toxicol Pharmacol 46:218–224.
  • Chi Z, Liu R, Zhao L, Qin P, Pan X, Sun F, 2009. A new strategy to probe the genotoxicity of silver nanoparticles combined with cetylpyridine bromide. Spectrochim Acta A Mol Biomol Spectrosc 72:577–581.
  • Choi JY, Lee SH, Na HB, An K, Hyeon T, Seo TS. 2010. In vitro cytotoxicity screening of water-dispersible metal oxide nanoparticles in human cell lines. Bioprocess Biosyst Eng 33:21–30.
  • Chompoosor A, Saha K, Ghosh PS, Macarthy DJ, Miranda OR, Zhu ZJ, 2010. The role of surface functionality on acute cytotoxicity, ROS generation and DNA damage by cationic gold nanoparticles. Small 6:2246–2249.
  • Collins AR, Dusinska M, Gedik CM, Stetina R. 1996. Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect 104:465–469.
  • Colognato R, Bonelli A, Ponti J, Farina M, Bergamaschi E, Sabbioni E, 2008. Comparative genotoxicity of cobalt nanoparticles and ions on human peripheral leukocytes in vitro. Mutagenesis 23:377–382.
  • Cooke MS, Evans MD, Dizdaroglu M, Lunec J. 2003. Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17:1195–1214.
  • Dandekar P, Dhumal R, Jain R, Tiwari D, Vanage G, Patravale V. 2010. Toxicological evaluation of pH-sensitive nanoparticles of curcumin: acute, sub-acute and genotoxicity studies. Food Chem Toxicol 48:2073–2089.
  • Dhawan A, Taurozzi JS, Pandey AK, Shan W, Miller SM, Hashsham SA, 2006. Stable colloidal dispersions of C60 fullerenes in water: evidence for genotoxicity. Environ Sci Technol 40:7394–7401.
  • Dhawan A, Sharma V, Parmar D. 2009. Nanomaterials: a challenge for toxicologists. Nanotoxicology 3:1–9.
  • 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.
  • Di Virgilio AL, Reigosa M, Arnal PM, Fernández 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.
  • Doak SH, Griffiths SM, Manshian B, Singh N, Williams PM, Brown AP, 2009. Confounding experimental considerations in nanogenotoxicology. Mutagenesis 24:285–293.
  • Donaldson K, Poland CA, Schins RP. 2010. Possible genotoxic mechanisms of nanoparticles: criteria for improved test strategies. Nanotoxicology 4:414–420.
  • Du H, Zhu X, Fan C, Xu S, Wang Y, Zhou Y. 2011. Oxidative damage and OGG1 expression induced by a combined effect of titanium dioxide nanoparticles and lead acetate in human hepatocytes. Environ Toxicol. [Epub ahead of print].
  • Dusinska M, Collins AR. 1996. Detection of oxidised purines and UV-induced photoproducts in DNA, by inclusion of lesion-specific enzymes in the comet assay (single cell gell electrophoresis). ATLA 24:405–411.
  • Dusinska M; NanoTEST consortium. 2009. Testing strategies for the safety of nanoparticles used in medical applications. Nanomedicine (Lond) 4:605–607.
  • Dusinska M, Fjellsbø LM, Magdolenova Z, Ravnum S, Rinna A, Rundén-Pran E. 2011. Safety of Nanoparticles in Medicine. In: Nanomedicine in Health and Disease. USA: Science Publishers, Chap. 11, pp. 203–226.
  • Dusinska M, Rundén-Dusinska M, Rundén-Pran E, Carreira SC, Saunders M. 2012. In vitro and in vivo toxicity test methods. Chapter 4. Critical evaluation of toxicity tests. In: Fadeel B, Pietroiusti A, Shvedova A, editors. Adverse effects of engineered nanomaterials: exposure, toxicology and impact on human health. Elsevier; pp. 63–84.
  • Ema M, Tanaka J, Kobayashi N, Naya M, Endoh S, Maru J, 2012. Genotoxicity evaluation of fullerene C60 nanoparticles in a comet assay using lung cells of intratracheally instilled rats. Regul Toxicol Pharmacol 2:419–424.
  • 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.
  • Estevanato L, Cintra D, Baldini N, Portilho F, Barbosa L, Martins O, 2011. Preliminary biocompatibility investigation of magnetic albumin nanosphere designed as a potential versatile drug delivery system. Int J Nanomed 6:1709–1717.
  • Falck GC, Lindberg HK, Suhonen S, Vippola M, Vanhala E, Catalán J, 2009. Genotoxic effects of nanosized and fine TiO2. Hum Exp Toxicol 28:339–352.
  • Fenech M, Kirsch-Volders M, Natarajan AT, Surralles J, Crott JW, Parry J, 2011. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis 26:125–132.
  • Flower NA, Brabu B, Revathy M, Gopalakrishnan C, Raja SV, Murugan SS, 2012. Characterization of synthesized silver nanoparticles and assessment of its genotoxicity potentials using the alkaline comet assay. Mutat Res 742:61–65.
  • Foldbjerg R, Dang DA, Autrup H. 2011. Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Arch Toxicol 85:743–750.
  • 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.
  • Franklin NM, Rogers NJ, Apte SC, Batley GE, Gadd GE, Casey PS. 2007. Comparative toxicity of nanoparticulate ZnO, bulkZnO, and ZnCl2 to a freshwater microalga (Pseudokirchneriella subcapitata): the importance of particle solubility. Environ Sci Technol 41:8484–8490.
  • Freitas MLL, Silva LP, Azevedo RB, Garcia VAP, Lacava LM, Grisolia CK, 2002. A double-coated magnetite-based magnetic fluid evaluation by cytometry and genetic tests. J Magn Magn Mater 252:396–398.
  • Galloway SM, Armstrong MJ, Reuben C, Colman S, Brown B, Cannon C, 1987. Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: evaluations of 108 chemicals. Environ Mol Mutagen 10(Suppl 10): 1–175.
  • Galloway SM, Aardema MJ, Ishidate M Jr, Ivett JL, Kirkland DJ, Morita T, 1994. Report from working group on in vitro tests for chromosomal aberrations. Mutat Res 312:241–261.
  • Guadagnini R, Halamoda B, Walker L, Pojana G, Magdolenova Z, Bilanicova D, 2013. Toxicity screenings of nanomaterials: challenges due to interference with assay processes and components of classic in vitro tests. Nanotoxicology, Special issue – supplement, in press.
  • Gojova A, Guo B, Kota RS, Rutledge JC, Kennedy IM, Barakat AI. 2007. Induction of inflammation in vascular endothelial cells by metal oxide nanoparticles: effect of particle composition. Environ Health Perspect 115:403–409.
  • Gonzalez L, Lison D, Kirsch-Volders M. 2008. Genotoxicity of engineered nanomaterials: a critical review. Nanotoxicology 2:252–273.
  • Gonzalez L, Sanderson BJ, Kirsch-Volders M. 2011. Adaptations of the in vitro MN assay for the genotoxicity assessment of nanomaterials. Mutagenesis 26:185–191.
  • Gonzalez L, Thomassen LC, Plas G, Rabolli V, Napierska D, Decordier I, 2010. Exploring the aneugenic and clastogenic potential in the nanosize range: A549 human lung carcinoma cells and amorphous monodisperse silica nanoparticles as models. Nanotoxicology 4:82–95.
  • Ghosh M, Bandyopadhyay M, Mukherjee A. 2010. Genotoxicity of titanium dioxide (TiO2) nanoparticles at two trophic levels: plant and human lymphocytes. Chemosphere 81:1253–62.
  • Green M, Howman E. 2005. Semiconductor quantum dots and free radical induced DNA nicking. Chem Commun 7:121–123.
  • 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.
  • 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.
  • Gurr JR, Wang AS, Chen CH, Jan KY. 2005. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology 213:66–73.
  • Hackenberg S, Friehs G, Froelich K, Ginzkey C, Koehler C, Scherzed A, 2010. Intracellular distribution, geno- and cytotoxic effects of nanosized titanium dioxide particles in the anatase crystal phase on human nasal mucosa cells. Toxicol Lett 195:9–14.
  • Hackenberg S, Friehs G, Kessler M, Froelich K, Ginzkey C, Koehler C, 2011c. Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ Mol Mutagen 52:264–268.
  • Hackenberg S, Scherzed A, Kessler M, Hummel S, Technau A, Froelich K, . 2011b. Silver nanoparticles: evaluation of DNA damage, toxicity and functional impairment in human mesenchymal stem cells. Toxicol Lett 201:27–33.
  • Hackenberg S, Scherzed A, Technau A, Kessler M, Froelich K, Ginzkey C, . 2011a. Cytotoxic, genotoxic and pro-inflammatory effects of zinc oxide nanoparticles in human nasal mucosa cells in vitro. Toxicol In Vitro 25:657–663.
  • Hackenberg S, Zimmermann FZ, Scherzed A, Friehs G, Froelich K, Ginzkey C, 2011d. Repetitive exposure to zinc oxide nanoparticles induces DNA damage in human nasal mucosa mini organ cultures. Environ Mol Mutagen 52:582–589.
  • Handy RD, Owen R, Valsami-Jones E. 2008. The ecotoxicology of nanoparticles and nanomaterials: current status, knowledge gaps, challenges, and future needs. Ecotoxicology 17:315–325.
  • Handy RD, van den Brink N, Chappell M, Mühling M, Behra R, Dušinská M, 2012. Practical considerations for conducting ecotoxicity test methods with manufactured nanomaterials: what have we learnt so far? Ecotoxicology 21:933–72.
  • Hansen SF, Larse BH, Olsen SI, Baun A. 2007. Categorization framework to aid hazard identification of nanomaterials. Nanotoxicology 1:243–250.
  • Hasegawa G, Shimonaka M, Ishihara Y. 2012. Differential genotoxicity of chemical properties and particle size of rare metal and metal oxide nanoparticles. J Appl Toxicol 32:72–80.
  • He L, Yang L, Zhang ZR, Gong T, Deng L, Gu Z, 2009. In vitro evaluation of the genotoxicity of a family of novel MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer and PLGA nanoparticles. Nanotechnology 20: 455102.
  • Hong SC, Lee JH, Lee J, Kim HY, Park JY, Cho J, 2011. Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups. Int J Nanomedicine 6:3219–3231.
  • http://cdb.iso.org
  • http://ec.europa.eu/environment/chemicals/nanotech/index.htm# definition
  • http://www.jacvam.jp/en_effort/en_oecd.html
  • Huang S, Chueh PJ, Lin YW, Shih TS, Chuang SM. 2009. Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-term exposure. Toxicol Appl Pharmacol 241:182–194.
  • Hudecová A, Kusznierewicz B, Hašplová K, Huk A, Magdolenová Z, Miadoková E, 2012a. Gentiana asclepiadea exerts antioxidant activity and enhances DNA repair of hydrogen peroxide- and silver nanoparticles-induced DNA damage. Food Chem Toxicol 50:3352–3359.
  • Hudecová A, Kusznierewicz B, Rundén-Pran E, Magdolenová Z, Hašplová K, Rinna A, 2012b. Silver nanoparticles induce pre-mutagenic DNA oxidation that can be prevented by phytochemicals from Gentiana asclepiadea. Mutagenesis 27:759–769.
  • Hwang do W, Lee DS, Kim S. 2012. Gene expression profiles for genotoxic effects of silica-free and silica-coated cobalt ferrite nanoparticles. J Nucl Med 53:106–112.
  • Iavicoli I, Leso V, Fontana L, Bergamaschi A. 2011. Toxicological effects of titanium dioxide nanoparticles: a review of in vitro mammalian studies. Eur Rev Med Pharmacol Sci 15:481–508.
  • 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.
  • Jacobsen NR, Møller P, Jensen KA, Vogel U, Ladefoged O, Loft S, 2009. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice. Part Fibre Toxicol. 12;6:2. doi: 10.1186/1743-8977-6-2. PubMed PMID: 19138394; PubMed Central PMCID: PMC2636756.
  • Jacobsen NR, Pojana G, White P, Møller P, Cohn CA, Korsholm KS, 2008. Genotoxicity, cytotoxicity, and reactive oxygen species induced by single-walled carbon nanotubes and C60 fullerenes in the FE1-mutaTMmouse lung epithelial cells. Environ Mol Mutagen 49:476–487.
  • Jacobsen NR, Saber AT, White P, Møller P, Pojana G, Vogel U, 2007. Increased mutant frequency by carbon black, but not quartz, in the lacZ and cII transgenes of muta mouse lung epithelial cells. Environ Mol Mutagen 48:451–461.
  • Jha AN. 2008. Ecotoxicological applications and significance of the comet assay. Mutagenesis 23:207–221.
  • Jiang H, Liu F, Yang H, Li Y. 2012. Effects of cobalt nanoparticles on human T cells in vitro. Biol Trace Elem Res 146:23–29.
  • Jin P, Chen Y, Zhang SB, Chen Z. 2011. Interactions between Al(12)X (X = Al, C, N and P) nanoparticles and DNA nucleobases/base pairs: implications for nanotoxicity. J Mol Model. [ Epub ahead of print ].
  • Jin Y, Kannan S, Wu M, Zhao JX. 2007. Toxicity of luminescent silica nanoparticles to living cells. Chem Res Toxicol 20:1126–1133.
  • Jugan ML, Barillet S, Simon-Deckers A, Herlin-Boime N, Sauvaigo S, Douki T, 2011. Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells. Nanotoxicology. [ Epub ahead of print].
  • 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.
  • 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.
  • Kang SJ, Lee YJ, Kim BM, Choi YJ, Chung HW. 2011. Cytotoxicity and genotoxicity of titanium dioxide nanoparticles in UVA-irradiated normal peripheral blood lymphocytes. Drug Chem Toxicol. 34:277–84.
  • Karlsson HL, Cronholm P, Gustafsson J, Möller L. 2008. Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol 21:1726–1732.
  • Karlsson HL, Gustafsson J, Cronholm P, Möller L. 2009. Size-dependent toxicity of metal oxide particles--a comparison between nano- and micrometer size. Toxicol Lett 188:112–118.
  • Karlsson HL. 2010. The comet assay in nanotoxicology research. Anal Bioanal Chem 398:651–666.
  • Kazimirova A, Magdolenova Z, Barancokova M, Staruchova M, Volkovova K, Dusinska M. 2012. Genotoxicity testing of PLGA-PEO nanoparticles in TK6 cells by the comet assay and the cytokinesis-block micronucleus assay. Mutat Res 748:42–47.
  • 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.
  • 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.
  • Kim JS, Yoon TJ, Yu KN, Kim BG, Park SJ, Kim HW, 2006. Toxicity and tissue distribution of magnetic nanoparticles in mice. Toxicol Sci 89:338–347.
  • Kim YS, Kim JS, Cho HS, Rha DS, Kim JM, Park JD, 2008. Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague-Dawley rats. Inhal Toxicol 20:575–583.
  • Kisin ER, Murray AR, Keane MJ, Shi XC, Schwegler-Berry D, Gorelik O, 2007. Single-walled carbon nanotubes: geno- and cytotoxic effects in lung fibroblast V79 cells. J Toxicol Environ Health Part A 70:2071–2079.
  • Kruszewski M, Brzoska K, Brunborg G, Asare N, Dobrzynska M, Dusinska M, 2011. Toxicity of silver nanomaterials in higher eukaryotes, in advances in molecular toxicology 5, Chap. 5, pp. 179–218.
  • Kulmala M. 2004. Formation and growth rates of ultrafine atmospheric particles: a review of observations. J Aerosol Sci 35:143–176.
  • Kumar A, Pandey AK, Singh SS, Shanker R, Dhawan A. 2011a. A flow cytometric method to assess nanoparticle uptake in bacteria. Cytometry A 79: 707–712.
  • 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.
  • Könczöl M, Ebeling S, Goldenberg E, Treude F, Gminski R, Gieré R, 2011. Cytotoxicity and genotoxicity of size-fractionated iron oxide (magnetite) in A549 human lung epithelial cells: role of ROS, JNK, and NF-κB. Chem Res Toxicol 24:1460–1475.
  • Laingam S, Froscio SM, Humpage AR. 2008. Flow-cytometric analysis of in vitro micronucleus formation: comparative studies with WIL2-NS human lymphoblastoid and L5178Y mouse lymphoma cell lines. Mutat Res 656:19–26.
  • Landsiedel R, Kapp MD, Schulz M, Wiench K, Oesch F. 2009. Genotoxicity investigations on nanomaterials: methods, preparation and characterization of test material, potential artifacts and limitations--many questions, some answers. Mutat Res 681:241–458.
  • Lewis DJ, Bruce C, Bohic S, Cloetens P, Hammond SP, Arbon D, 2010. Intracellular synchrotron nanoimaging and DNA damage/genotoxicity screening of novel lanthanide-coated nanovectors. Nanomedicine (Lond) 5:1547–1557.
  • Li CH, Shen CC, Cheng YW, Huang SH, Wu CC, Kao CC, 2011c. Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice. Nanotoxicology. [ Epub ahead of print].
  • Li JJ, Lo SL, Ng CT, Gurung RL, Hartono D, Hande MP, . 2011a. Genomic instability of gold nanoparticle treated human lung fibroblast cells. Biomaterials 32:5515–5523.
  • Li Y, Chen DH, Yan J, Chen Y, Mittelstaedt RA, Zhang Y, 2012. Genotoxicity of silver nanoparticles evaluated using the Ames test and in vitro micronucleus assay. Mutat Res 745:4–10.
  • Li Y, Sun L, Jin M, Du Z, Liu X, Guo C, . 2011b. Size-dependent cytotoxicity of amorphous silica nanoparticles in human hepatoma HepG2 cells. Toxicol In Vitro. [ Epub ahead of print].
  • Liang XJ, Chen C, Zhao Y, Jia L, Wang PC. 2008. Biopharmaceutics and therapeutic potential of engineered nanomaterials. Curr Drug Metab 9:697–709.
  • Lin W, Xu Y, Huang C, Ma Y, Shannon KB, Chen DR, 2009. Toxicity of nano- and micro-sized ZnO particles in human lungepithelial cells. J Nanopart Res 11:25–39.
  • Maenosono S, Suzuki T, Saita S. 2007. Mutagenicity of water-soluble FePt nanoparticles in Ames test. J Toxicol Sci 32:575–579.
  • 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.
  • Magdolenova Z, Bilaničová D, Pojana G, Fjellsbø LM, Hudecova A, Hasplova K, . 2012a. Impact of agglomeration and different dispersions of titanium dioxide nanoparticles on the human related in vitro cytotoxicity and genotoxicity. J Environ Monit 14:455–464.
  • Magdolenova Z, Lorenzo Y, Collins A, Dusinska M. 2012b. Can standard genotoxicity tests be applied to nanoparticles? J Toxicol Environ Health A Part A 75:1–7.
  • Mahmoudi M, Simchi A, Imani M, Shokrgozar MA, Milani AS, Häfeli UO, 2010. A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles. Colloids Surf B Biointerfaces 75:300–309.
  • Matsuda S, Matsui S, Shimizu Y, Matsuda T. 2011. Genotoxicity of colloidal fullerene C60. Environ Sci Technol 45:4133–4138.
  • McNeil SE. 2005. Nanotechnology for the biologist. J Leukoc Biol 78:585–94.
  • Merhi M, Dombu CY, Brient A, Chang J, Platel A, Le Curieux F, 2012. Study of serum interaction with a cationic nanoparticle: Implications for in vitro endocytosis, cytotoxicity and genotoxicity. Int J Pharm 423:37–44.
  • Monopoli MP, Walczyk D, Lowry-Campbell A, Elia G, Lynch I, Baldelli Bombelli F, 2011. Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. J Am Chem Soc 133:2525–2534.
  • Moreira S, Silva NB, Almeida-Lima J, Rocha HA, Medeiros SR, Alves Jr C, 2009. BC nanofibres: in vitro study of genotoxicity and cell proliferation. Toxicol Lett 189:235–241.
  • Moreno-Villanueva M, Eltze T, Dressler D, Bernhardt J, Hirsch C, Wick P, 2011. The automated FADU-assay, a potential high-throughput in vitro method for early screening of DNA breakage. ALTEX 28:295–303.
  • Mori T, Takada H, Ito S, Matsubayashi K, Miwa N, Sawaguchi T. 2006. Preclinical studies on safety of fullerene upon acute oral administration and evaluation for no mutagenesis. Toxicology 225:48–54.
  • Mortelmans K, Zeiger E. 2000. The Ames Salmonella/microsome mutagenicity assay. Mutat Res 455:29–60.
  • Mroz RM, Schins RP, Li H, Drost EM, Macnee W, Donaldson K. 2007. Nanoparticle carbon black driven DNA damage induces growth arrest and AP-1 and NFkappaB DNA binding in lung epithelial A549 cell line. J Physiol Pharmacol 58:461–470.
  • Mroz RM, Schins RP, Li H, Jimenez LA, Drost EM, Holownia A, 2008. Nanoparticle-driven DNA damage mimics irradiation-related carcinogenesis pathways. Eur Respir J 31:241–251.
  • Muller J, Decordier I, Hoet PH, Lombaert N, Thomassen L, Huaux F, 2008. Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells. Carcinogenesis 29:427–433.
  • Naha PC, Bhattacharya K, Tenuta T, Dawson KA, Lynch I, Gracia A, 2010. Intracellular localisation, geno- and cytotoxic response of polyN-isopropylacrylamide (PNIPAM) nanoparticles to human keratinocyte (HaCaT) and colon cells (SW 480). Toxicol Lett 198:134–143.
  • Naya M, Kobayashi N, Ema M, Kasamoto S, Fukumuro M, Takami S, 2012. In vivo genotoxicity study of titanium dioxide nanoparticles using comet assay following intratracheal instillation in rats. Regul Toxicol Pharmacol 62:1–6.
  • Nelson BC, Petersen EJ, Marquis BJ, Atha DH, Elliott JT, Cleveland D, 2011. NIST gold nanoparticle reference materials do not induce oxidative DNA damage. Nanotoxicology. [ Epub ahead of print].
  • Ng CT, Li JJ, Bay BH, Yung LY. 2010. Current studies into the genotoxic effects of nanomaterials. J Nucleic Acids.
  • Nohynek GJ, Dufour EK, Roberts MS. 2008. Nanotechnology, cosmetics and the skin: is there a health risk? Skin Pharmacol Physiol 21:136–149.
  • NRC. 1983. National Research Council. Risk assessment in the federal government: managing the process. Washington, DC: National Academy Press.
  • Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, 2005a. ILSI Research Foundation/Risk Science Institute Nanomaterial Toxicity Screening Working Group. Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol. 2:8. 10.1186/1743-8977-2-8 PMCID: PMC1260029.
  • Oberdörster G, Oberdörster E, Oberdörster J. 2005b. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839.
  • OECD Guideline for testing of chemicals, OECD 475. Mammalian Bone Marrow Chromosome Aberration Test, Adopted: 21st July 1997.
  • OECD Guideline for testing of chemicals, OECD 476. In vitro Mammalian Cell Gene Mutation Test, Adopted 4 April 1984, last updated 21 July 1997.
  • OECD Guideline for testing of chemicals. DRAFT PROPOSAL FOR A NEW GUIDELINE 487. In Vitro Mammalian Cell Micronucleus Test (MNvit), DRAFT TEST GUIDELINE, December 13, 2007 (Version 3).
  • OECD Guideline for testing of chemicals. OECD 471. Bacterial Reverse Mutation Test, Adopted 21st July 1997.
  • OECD Guideline for testing of chemicals. OECD 473. In vitro Mammalian Chromosomal Aberration Test, Adopted 21 July 1997.
  • OECD Guideline for testing of chemicals. OECD 474. Mammalian Erythrocyte Micronucleus Test, Adopted: 21st July 1997.
  • 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 (Lond) 5:1193–1203.
  • Papageorgiou I, Brown C, Schins R, Singh S, Newson R, Davis S, 2007. The effect of nano- and micron-sized particles of cobalt-chromium alloy on human fibroblasts in vitro. Biomaterials 28:2946–2958.
  • PAS71. 2005. Publicly Available Specification. Vocabulary- Nanoparticles. British Standards Institution (BSI).
  • Petković J, Zegura B, Stevanović M, Drnovšek N, Uskoković D, Novak S, 2011. DNA damage and alterations in expression of DNA damage responsive genes induced by TiO(2) nanoparticles in human hepatoma HepG2 cells. Nanotoxicology 5:341–53.
  • 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(3):035102. doi: 10.1088/0957-4484/21/3/035102. Epub . PubMed PMID: 19966402.
  • Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WA, Seaton A, 2008. Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotechnol 3:423–428.
  • Ponti J, Sabbioni E, Munaro B, Broggi F, Marmorato P, Franchini F, 2009. Genotoxicity and morphological transformation induced by cobalt nanoparticles and cobalt chloride: an in vitro study in Balb/3T3 mouse fibroblasts. Mutagenesis 24:439–445.
  • Rahman Q, Lohani M, Dopp E, Pemsel H, Jonas L, Weiss DG, 2002. Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. Environ Health Perspect 110:797–800.
  • Reeves JF, Davies SJ, Dodd NJ, Jha AN. 2008. Hydroxyl radicals (*OH) are associated with titanium dioxide (TiO2) nanoparticle-induced cytotoxicity and oxidative DNA damage in fish cells. Mutat Res 640:113–122.
  • 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.
  • Robertazzi A, Platts JA. 2005. Binding of transition metal complexes to guanine and guanine-cytosine: hydrogen bonding and covalent effects. J Biol Inorg Chem 10:854–866.
  • Sadeghiani N, Barbosa LS, Silva LP, Azevedo RB, Morais PC, Lacava ZGM. 2005. Genotoxicity and inflammatory investigation in mice treated with magnetite nanoparticles surface coated with polyaspartic acid. J Magn Magn Mater 289:466–468.
  • Saquib Q, Al-Khedhairy AA, Siddiqui MA, Abou-Tarboush FM, Azam A, Musarrat J. 2012. Titanium dioxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in human amnion epithelial (WISH) cells. Toxicol In Vitro 26:351–361.
  • Sayes CM, Reed KL, Glover KP, Swain KA, Ostraat ML, Donner EM, 2010. Changing the dose metric for inhalation toxicity studies: short-term study in rats with engineered aerosolized amorphous silica nanoparticles. Inhal Toxicol 22:348–354.
  • Sayes CM, Reed KL, Warheit DB. 2007. Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol Sci 97:163–180.
  • Schins RP. 2002. Mechanisms of genotoxicity of particles and fibers. Inhal Toxicol 14:57–78.
  • Schulz M, Ma-Hock L, Brill S, Strauss V, Treumann S, Gröters S, 2012. Investigation on the genotoxicity of different sizes of gold nanoparticles administered to the lungs of rats. Mutat Res 745:51–57.
  • Sharma V, Anderson D, Dhawan A. 2012. Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis 17:852–870.
  • 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.
  • 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.
  • Shukla RK, Kumar A, Gurbani D, Pandey AK, Singh S, Dhawan A. 2011b. TiO(2) nanoparticles induce oxidative DNA damage and apoptosis in human liver cells. Nanotoxicology. [ Epub ahead of print].
  • Shukla RK, Sharma V, Pandey AK, Singh S, Sultana S, Dhawan A. 2011a. ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells. Toxicol In Vitro 25:231–241.
  • Singh N, Jenkins GJ, Nelson BC, Marquis BJ, Maffeis TG, Brown AP, 2012. The role of iron redox state in the genotoxicity of ultrafine superparamagnetic iron oxide nanoparticles. Biomaterials 33:163–170.
  • Singh N, Manshian B, Jenkins GJ, Griffiths SM, Williams PM, Maffeis TG, 2009. NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 30:3891–3914.
  • Som C, Berges M, Chaudhry Q, Dusinska M, Fernandes TF, Olsen SI, 2010. The importance of life cycle concepts for the development of safe nanoproducts. Toxicology 269:160–169.
  • 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.
  • Stone V, Johnston H, Schins RP. 2009. Development of in vitro systems for nanotoxicology: methodological considerations. Crit Rev Toxicol 39:613–626.
  • Stone V, Nowack B, Baun A, van den Brink N, Kammer F, Dusinska M, 2010. Nanomaterials for environmental studies: classification, reference material issues, and strategies for physico-chemical characterisation. Sci Total Environ 408:1745–1754.
  • Sycheva LP, Zhurkov VS, Iurchenko VV, Daugel-Dauge NO, Kovalenko MA, Krivtsova EK, 2011. Investigation of genotoxic and cytotoxic effects of micro- and nanosized titanium dioxide in six organs of mice in vivo. Mutat Res 726:8–14.
  • 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.
  • Toyooka T, Amano T, Ibuki Y. 2012. Titanium dioxide particles phosphorylate histone H2AX independent of ROS production. Mutat Res 742:84–91.
  • 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.
  • Uboldi C, Giudetti G, Broggi F, Gilliland D, Ponti J, Rossi F. 2012. Amorphous silica nanoparticles do not induce cytotoxicity, cell transformation or genotoxicity in Balb/3T3 mouse fibroblasts. Mutat Res 745:11–20.
  • USEPA. 2007. Nanotechnology White Paper. Science Policy Council. United States Environmental Protection Agency. EPA100B-07001.
  • Vega-Villa KR, Takemoto JK, Yáñez JA, Remsberg CM, Forrest ML, Davies NM. 2008. Clinical toxicities of nanocarrier systems. Adv Drug Deliv Rev 60:929–938.
  • Vevers WF, Jha AN. 2008. Genotoxic and cytotoxic potential of titanium dioxide (TiO2) nanoparticles on fish cells in vitro. Ecotoxicology 17:410–420.
  • Vidal AE, Hickson ID, Boiteux I, Radicella JP. 2001. Mechanism of stimulation of the DNA glycosylase activity of hOGG1 by the major human AP endonuclease: bypass of the AP lyase activity step. Nucleic Acids Res 29:1285–1292.
  • Walczyk D, Bombelli F.B, Monopoli M.P, Lynch I, Dawson K.A. 2010. What the cell “sees" in Bionanoscience. J Am Chem Soc 132:5761–5768.
  • Wang JJ, Sanderson BJ, Wang H. 2007c. Cytotoxicity and genotoxicity of ultrafine crystalline SiO2 particulate in cultured human lymphoblastoid cells. Environ Mol Mutagen 48:151–157.
  • Wang JJ, Sanderson BJ, Wang H. 2007a. Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells. Mutat Res 628:99–106.
  • Wang JJ, Wang H, Sanderson BJ. 2007b. Ultrafine quartz-induced damage in human lymphoblastoid cells in vitro using three genetic damage end-points. Toxicol Mech Methods 17:223–232.
  • Wang L, Zhang J, Zheng Y, Yang J, Zhang Q, Zhu X. 2010. Bioeffects of CdTe quantum dots on human umbilical vein endothelial cells. J Nanosci Nanotechnol 10:8591–8596.
  • Wang S, Hunter LA, Arslan Z, Wilkerson MG, Wickliffe JK. 2011b. Chronic exposure to nanosized, anatase titanium dioxide is not cyto- or genotoxic to Chinese hamster ovary cells. Environ Mol Mutagen 52:614–622.
  • Wang S, Lawson R, Ray PC, Yu H. 2011a. Toxic effects of gold nanoparticles on Salmonella typhimurium bacteria. Toxicol Ind Health 27:547–554.
  • Warheit DB, Donner EM. 2010. Rationale of genotoxicity testing of nanomaterials: regulatory requirements and appropriateness of available OECD test guidelines. Nanotoxicology 4:409–413.
  • Warheit DB, 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.
  • Warheit DB. 2008. How meaningful are the results of nanotoxicity studies in the absence of adequate material characterization? Toxicol Sci 101:183–185.
  • Wessels A, Van Berlo D, Boots AW, Gerloff K, Scherbart AM, Cassee FR, 2011. Oxidative stress and DNA damage responses in rat and mouse lung to inhaled carbon nanoparticles. Nanotoxicology 5:66–78.
  • 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.
  • Wojewódzka M, Lankoff A, Dusinska M, Brunborg G, Czerwińska J, Iwaneńko T, 2011. Treatment with silver nanoparticles delays repair of X-ray induced DNA damage in HepG2 cells. Nukleonika 56: 29–33.
  • Wu W, Chen B, Cheng J, Wang J, Xu W, Liu L, 2010. Biocompatibility of Fe3O4/DNR magnetic nanoparticles in the treatment of hematologic malignancies. Int J Nanomedicine 5:1079–1084.
  • Xie H, Mason MM, Wise JP Sr. 2011. Genotoxicity of metal nanoparticles. Rev Environ Health 26:251–268.
  • 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. 6:3. doi: 10.1186/1743-8977-6-3. PubMed PMID: 19154577; PubMed Central PMCID: PMC2650674.
  • Xu L, Li X, Takemura T, Hanagata N, Wu G, Chou LL. 2012. Genotoxicity and molecular response of silver nanoparticle (NP)-based hydrogel. J Nanobiotechnology. [ Epub ahead of print].
  • 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.
  • Yin H, Casey PS, McCall MJ, Fenech M. 2010. Effects of surface chemistry on cytotoxicity, genotoxicity, and the generation of reactive oxygen species induced by ZnO nanoparticles. 21. Langmuir 26:15399–408.
  • Yoshida R, Kitamura D, Maenosono S. 2009. Mutagenicity of water-soluble ZnO nanoparticles in Ames test. J Toxicol Sci 34:119–122.
  • Zhu L, Chang DW, Dai L, Hong Y. 2007. DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. Nano Lett 7:3592–3597.

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