Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: Carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

International Journal of Nanomedicine

Volumn 9, Issue , 2014, Pages 271-286

  Kwon, Jee Young ^a   Koedrith, Preeyaporn ^b   Seo, Young Rok ^a  

^a Dongguk University   (South Korea)

^b MAHIDOL UNIVERSITY   (Thailand)

Author keywords

Carcinogenicity; Exposure assessment; Genotoxicity; Nanoparticles; Risk evaluation

Indexed keywords

ASBESTOS; CARBON NANOTUBE; COPPER NANOPARTICLE; LIPOSOME; MACROGOL 2000; MAGNETIC NANOPARTICLE; POLYLACTIDE; SILICA NANOPARTICLE; SUNSCREEN; ZINC OXIDE NANOPARTICLE; BIOLOGICAL MARKER; NANOPARTICLE; SILICON DIOXIDE; ZINC OXIDE;

ARTIFACT; BIOCOMPATIBILITY; CARCINOGENESIS; CARCINOGENICITY; CHROMOSOME ABERRATION; CYTOTOXICITY; DNA DAMAGE; DNA STRAND BREAKAGE; ENVIRONMENTAL EXPOSURE; GENE MUTATION; GENOTOXICITY; HUMAN; HYDROGEL; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; MATERIAL COATING; MICELLE; NANOTOXICOLOGY; NONHUMAN; OXIDATIVE DNA DAMAGE; OXIDATIVE STRESS; PARTICLE SIZE; PHOTOTOXICITY; PHYSICAL CHEMISTRY; REVIEW; SURFACE AREA; SURFACE CHARGE; ANIMAL; CELL LINE; DRUG EFFECTS; MOUSE; MUTAGEN TESTING;

ANIMALS; ARTIFACTS; BIOMARKERS; CELL LINE; DNA DAMAGE; HUMANS; MICE; MUTAGENICITY TESTS; NANOPARTICLES; SILICON DIOXIDE; ZINC OXIDE;

EID: 84938223264     PISSN: 11769114     EISSN: 11782013     Source Type: Journal    
DOI: 10.2147/IJN.S57918     Document Type: Review

References (192)

1. Singh N, Manshian B, Jenkins GJ, et al. NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials. 2009;30(23–24):3891–3914.
2. Lux report. Nanomaterials state of the market: stealth success, broad impact. Available from: http://portal.luxresearchinc.com/research/document/3735. Accessed January 17, 2008.
3. Brown C, Fisher J, Ingham E. Biological effects of clinically relevant wear particles from metal-on-metal hip prostheses. Proc Inst Mech Eng H. 2006;220(2):355–369.
4. Ballestri M, Baraldi A, Gatti AM, et al. Liver and kidney foreign bodies granulomatosis in a patient with malocclusion, bruxism, and worn dental prostheses. Gastroenterology. 2001;121(5):1234–1238.
5. Hart AJ, Hester T, Sinclair K, et al. The association between metal ions from hip resurfacing and reduced T-cell counts. J Bone Joint Surg Br. 2006;88(4):449–454.
6. Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005;5(3):161–171.
7. Sahoo SK, Parveen S, Panda JJ. The present and future of nanotechnology in human health care. Nanomedicine. 2007;3(1):20–31.
8. Du X, He J. Elaborate control over the morphology and structure of mercapto-functionalized mesoporous silicas as multipurpose carriers. Dalton Trans. 2010;39(38):9063–9072.
9. Ma S WY, Zhu Y. A simple room temperature synthesis of mesoporous silica nanoparticles for drug storage and pressure pulsed delivery. Journal of Porous Material. 2011;18(2):233–239.
10. Barick KC, Nigam S, Bahadur D. Nanoscale assembly of mesoporous ZnO: a potential drug carrier. J Mater Chem. 2010;20:6446–6452.
11. Borm PJA, Berube D. A tale of opportunities, uncertainties and risks. Nano Today. 2008;3:56–59.
12. Dusinska M, Fjellsbo L, Magdolenova Z, et al. Testing strategies for the safety of nanoparticles used in medical applications. Nanomedicine (Lond). 2009;4(6):605–607.
13. Kumar A, Pandey A, Shanker R, Dhawan A. Microorganism: a versatile model for toxicity assessment of engineered nanomaterials. In: Cioffi N, Rai M, editors. Nano-Antimicrobials: Progress and Prospects. Berlin, Germany: Springer Verlag GmbH, 2012.
14. Maynard AD. Nanotechnology: the next big thing, or much ado about nothing? Ann Occup Hyg. 2007;51:1–12.
15. Elsaesser A, Howard CV. Toxicology of nanoparticles. Adv Drug Deliv Rev. 2012;64(2):129–137.
16. Navarro E, Baun A, Behra R, et al. Environmental behavior and ecotoxicity of engineered nanoparticles to algae, plants, and fungi. Ecotoxicology. 2008;17(5):372–386.
17. Kumar A, Pandey AK, Singh SS, Shanker R, Dhawan A. A flow cytometric method to assess nanoparticle uptake in bacteria. Cytometry A. 2011;79(9):707–712.
18. Aitken RJ, Koopman P, Lewis SE. Seeds of concern. Nature. 2004; 432(7013):48–52.
19. Aitken RJ HS, Tran CL, Donaldson K, et al. Multidisciplinary approach to the identification of reference materials for engineered nanoparticle toxicology. Nanotoxicology. 2008;2:71–78.
20. Feliu N, Fadeel B. Nanotoxicology: no small matter. Nanoscale. 2010;2(12):2514–2520.
21. Pan H, House MG, Hao X, Jiang HW. Fabrication and characterization of a silicon metal-oxide-semiconductor based triple quantum dot. Appl Phys Lett. 2012;100(263109):1–5.
22. Shpaisman N, Givan U, Kwiat M, Pevzner A, Elnathan R, Patolsky F. Controlled synthesis of ferromagnetic semiconducting silicon nanotubes. J Phys Chem C. 2012;116(14):8000–8007.
23. Sachet E, Losego MD, Guske J, Franzen S, Maria JP. Mid-infrared surface plasmon resonance in zinc oxide semiconductor thin films. Appl Phys Lett. 2013;102(5):051111–051114.
24. Rowe DJ, Jeong JS, Mkhoyan KA, Kortshagen UR. Phosphorus-doped silicon nanocrystals exhibiting mid-infrared localized surface plasmon resonance. Nano Lett. 2013;13(3):1317–1322.
25. Zhou WJ, Halpern AR, Seefeld TH, Corn RM. Near infrared surface plasmon resonance phase imaging and nanoparticle-enhanced surface plasmon resonance phase imaging for ultrasensitive protein and DNA biosensing with oligonucleotide and aptamer microarrays. Anal Chem. 2012;84(1):440–445.
26. Joshi R, Feldmann V, Koestner W, et al. Multifunctional silica nanoparticles for optical and magnetic resonance imaging. Biological Chemistry. 2013;394(1):125–135.
27. Orlov AF, Agagonov Y, Balagurov LA, Bublik VT, et al. Study of structural characteristics of ferromagnetic silicon implanted with manganese. Crystallography Reports. 2008;53(5):796–799.
28. Science Daily. Nanoparticle. Available from: http://www.sciencedaily.com/articles/n/nanoparticle.htm. Accessed February 17, 2013.
29. Dufour EK, Kumaravel T, Nohynek GJ, Kirkland D, Toutain H. 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. 2006; 607(2):215–224.
30. Yuan Fangli HP, Yin Chunlei, Huang Shulan, Li Jinlin. Preparation and properties of zinc oxide nanoparticles coated with zinc aluminate. J Mater Chem. 2003;13:634–637.
31. Qi Qi TZ, Qingjiang Yu, Rui Wang, Yi Zeng, Li Liu, Haibin Yang. Properties of humidity sensing ZnO nanorods-base sensor fabricated by screen-printing. Sens Actuators B Chem. 2008;133:638–643.
32. Sayes CM, Reed KL, Warheit DB. Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol Sci. 2007;97(1):163–180.
33. Jeng HA, Swanson J. Toxicity of metal oxide nanoparticles in mammalian cells. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2006;41(12):2699–2711.
34. Kumar A, Dhawan A. Genotoxic and carcinogenic potential of engineered nanoparticles: an update. Arch Toxicol. 2013;87(11):1883–1900.
35. Manke A, Wang L, Rojanasakul Y. Mechanisms of nanoparticle-induced oxidative stress and toxicity. Biomed Res Int. 2013;2013:942916.
36. Sharma V, Singh P, Pandey AK, Dhawan A. Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutat Res. 2012;745(1–2):84–91.
37. Surekha P, Kishore AS, Srinivas A, et al. Repeated dose dermal toxicity study of nano zinc oxide with Sprague-Dawley rats. Cutan Ocul Toxicol. 2012;31(1):26–32.
38. Rob J Vandebriel, Wim H De Jong. A review of mammalian toxicity of ZnO nanoparticles. Nanotechnol Sci Appl. 2012;5:61–71.
39. Sharma V, Shukla RK, Saxena N, Parmar D, Das M, Dhawan A. DNA damaging potential of zinc oxide nanoparticles in human epidermal cells. Toxicol Lett. 2009;185(3):211–218.
40. Yeon Sue Jang, Eun Young Lee, Yoon-Hee Park. The potential for skin irritation, phototoxicity, and sensitization of ZnO nanoparticles. Mol Cell Toxicol. 2012;8(2):171–177.
41. Seung Ho Lee, Jae Eun Pie, Yu Ri Kim, Hee Ra Lee, Sang Wook Son, Meyoung-Kon Kim. Effects of zinc oxide nanoparticles on gene expression profile in human keratinocytes. Mol Cell Toxicol. 2012; 8(2):113–118.
42. SCCNFP. The scientific committee on cosmetic products and non-food products intended for consumers concerning zinc oxide. 2003. Available from: http://ec.europa.eu/health/ph_risk/committees/sccp/documents/out222_en.pdf. Accessed April 15, 2014.
43. Wang SQ, Balagula Y, Osterwalder U. Photoprotection: a review of the current and future technologies. Dermatol Ther. 2010;23(1):31–47.
44. Tran DT, Salmon R. Potential photocarcinogenic effects of nanoparticle sunscreens. Australas J Dermatol. 2011;52(1):1–6.
45. Kaewamatawong T, Shimada A, Okajima M, et al. Acute and subacute pulmonary toxicity of low dose of ultrafine colloidal silica particles in mice after intratracheal instillation. Toxicol Pathol. 2006;34(7):958–965.
46. Lin W, Huang YW, Zhou XD, Ma Y. In vitro toxicity of silica nanoparticles in human lung cancer cells. Toxicol Appl Pharmacol. 2006; 217(3):252–259.
47. Chang JS, Chang KL, Hwang DF, Kong ZL. In vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. Environ Sci Technol. 2007; 41(6):2064–2068.
48. Jin Y, Kannan S, Wu M, Zhao JX. Toxicity of luminescent silica nanoparticles to living cells. Chem Res Toxicol. 2007;20(8):1126–1133.
49. Chen M, von Mikecz A. Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Exp Cell Res. 2005;305(1):51–62.
50. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006;160(1):1–40.
51. Barnes CA, Elsaesser A, Arkusz J, et al. Reproducible comet assay of amorphous silica nanoparticles detects no genotoxicity. Nano Lett. 2008;8(9):3069–3074.
52. Wang JJ, Sanderson BJ, Wang H. Cytotoxicity and genotoxicity of ultrafine crystalline SiO2 particulate in cultured human lymphoblastoid cells. Environ Mol Mutagen. 2007;48(2):151–157.
53. Fruijtier-Polloth C. The toxicological mode of action and the safety of synthetic amorphous silica-a nanostructured material. Toxicology. 2012;294(2–3):61–79.
54. Park YH, Bae CH, Jang Y. Effect of the size and surface charge of silica nanoparticles on cutaneous toxicity. Mol Cell Toxicol. 2013;9(1): 67–74.
55. Musa M, Kannan TP, Masudi SM, Ab Rahman I. Assessment of DNA damage caused by locally produced hydroxyapatite-silica nanocomposite using comet assay on human lung fibroblast cell line. Mol Cell Toxicol. 2012;8(1):53–60.
56. Choi JE, Park Y-H, Young Lee E. A safety assessment of phototoxicity and sensitization of SiO2 nanoparticles. Mol Cell Toxicol. 2011;7(2):171–176.
57. Kim Y-J, Ik Yang S. Neurotoxic effects by silica TM nanoparticle is independent of differentiation of SH-SY5Y cells. Mol Cell Toxicol. 2011;7(4):381–388.
58. Yoshida T, Yoshioka Y, Matsuyama K, et al. Surface modification of amorphous nanosilica particles suppresses nanosilica-induced cytotoxicity, ROS generation, and DNA damage in various mammalian cells. Biochem Biophys Res Commun. 2012;427(4):748–752.
59. Wang F, Jiao C, Liu J, Yuan H, Lan M, Gao F. Oxidative mechanisms contribute to nanosize silican dioxide-induced developmental neurotoxicity in PC12 cells. Toxicol In Vitro. 2011;25(8):1548–1556.
60. 2 on human epithelial intestinal HT-29 cell line. Ann Occup Hyg. 2012;56(5):622–630.
61. Passagne I, Morille M, Rousset M, Pujalte I, L’Azou B. Implication of oxidative stress in size-dependent toxicity of silica nanoparticles in kidney cells. Toxicology. 2012;299(2–3):112–124.
62. Nabeshi H, Yoshikawa T, Matsuyama K, et al. Amorphous nanosilica induce endocytosis-dependent ROS generation and DNA damage in human keratinocytes. Part Fibre Toxicol. 2011;8:1.
63. Landsiedel R, Ma-Hock L, Van Ravenzwaay B, et al. Gene toxicity studies on titanium dioxide and zinc oxide nanomaterials used for UV-protection in cosmetic formulations. Nanotoxicology. 2010;4:364–381.
64. Li CH, Shen CC, Cheng YW, et al. Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice. Nanotoxicology. 2012;6(7):746–756.
65. Monteiro-Riviere NA, Wiench K, Landsiedel R, Schulte S, Inman AO, Riviere JE. Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in UVB sunburned skin: an in vitro and in vivo study. Toxicol Sci. 2011;123(1):264–280.
66. Gopalan R, Osman I, Amani A, Matas M, Anderson D. The effect of zinc oxide and titanium dioxide nanoparticles in the comet assay with UVA photoactivation of human sperm and lymphocytes. Nanotoxicology. 2009;3(1):33–39.
67. Gerloff K, Albrecht C, Boots AW, Förster I, Schins RPF. Cytotoxicity and oxidative DNA damage by nanoparticles in human intestinal Caco-2 cells. Nanotoxicology. 2009;3(4):355–364.
68. Yang H, Liu C, Yang D, Zhang H, Xi Z. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition. J Appl Toxicol. 2009;29(1):69–78.
69. Yoshida R, Kitamura D, Maenosono S. Mutagenicity of water-soluble ZnO nanoparticles in Ames test. J Toxicol Sci. 2009;34(1):119–122.
70. Osman IF, Baumgartner A, Cemeli E, Fletcher JN, Anderson D. Genotoxicity and cytotoxicity of zinc oxide and titanium dioxide in HEp-2 cells. Nanomedicine (Lond). 2010;5(8):1193–1203.
71. Yin H, Casey PS, McCall MJ, Fenech M. Effects of surface chemistry on cytotoxicity, genotoxicity, and the generation of reactive oxygen species induced by ZnO nanoparticles. Langmuir. 2010;26(19): 15399–15408.
72. Sharma V, Anderson D, Dhawan A. Zinc oxide nanoparticles induce oxidative stress and genotoxicity in human liver cells (HepG2). J Biomed Nanotechnol. 2011;7(1):98–99.
73. Sharma V, Singh SK, Anderson D, Tobin DJ, Dhawan A. Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes. J Nanosci Nanotechnol. 2011;11(5):3782–3788.
74. Hackenberg S, Zimmermann FZ, Scherzed A, et al. Repetitive exposure to zinc oxide nanoparticles induces dna damage in human nasal mucosa mini organ cultures. Environ Mol Mutagen. 2011;52(7):582–589.
75. Yin H, Casey PS, McCall MJ. Surface modifications of ZnO nanoparticles and their cytotoxicity. J Nanosci Nanotechnol. 2010;10(11): 7565–7570.
76. Zhang XQ, Yin LH, Tang M, Pu YP. ZnO, TiO(2), SiO(2,) and Al(2)O(3) nanoparticles-induced toxic effects on human fetal lung fibroblasts. Biomed Environ Sci. 2011;24(6):661–669.
77. Xia T, Kovochich M, Liong M, et al. Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano. 2008;2(10): 2121–2134.
78. De Berardis B, Civitelli G, Condello M, et al. Exposure to ZnO nanoparticles induces oxidative stress and cytotoxicity in human colon carcinoma cells. Toxicol Appl Pharmacol. Epub April 29, 2010.
79. Sharma V, Anderson D, Dhawan A. Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis. 2012;17(8): 852–870.
80. Alarifi S, Ali D, Alkahtani S, et al. Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles. Int J Nanomedicine. 2013;8:983–993.
81. Guo D, Bi H, Liu B, Wu Q, Wang D, Cui Y. Reactive oxygen species-induced cytotoxic effects of zinc oxide nanoparticles in rat retinal ganglion cells. Toxicol In Vitro. 2013;27(2):731–738.
82. Johnston CJ, Driscoll KE, Finkelstein JN, et al. Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica. Toxicol Sci. 2000;56(2):405–413.
83. Sayes CM, Reed KL, Glover KP, et al. Changing the dose metric for inhalation toxicity studies: short-term study in rats with engineered aerosolized amorphous silica nanoparticles. Inhal Toxicol. 2010;22(4): 348–354.
84. Liu X, Keane MJ, Zhong BZ, Ong TM, Wallace WE. Micronucleus formation in V79 cells treated with respirable silica dispersed in medium and in simulated pulmonary surfactant. Mutat Res. 1996; 361(2–3):89–94.
85. ECETOC. European Centre for Ecotoxicology and Toxicology of Chemicals. Synthetic amorphous silica (CAS No 7631–86–9). Brussels, Belgium: JACC Report; 2006:237.
86. EPA. US Environmental Protection Agency. Screening-level hazard characterization of silane, dichlorodimethyl-, reaction product with silica (CASRN 68611–44–9); 2011.
87. OECD. Organisation for Economic Co-operation and Development. SIDS dossier on synthetic amorphous silica and silicates; 2004.
88. Yang K, Lin D, Xing B. Interactions of humic acid with nanosized inorganic oxides. Langmuir. 2009;25(6):3571–3576.
89. Gonzalez L, Thomassen LC, Plas G, et al. 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.
90. Park MV, Verharen HW, Zwart E, et al. Genotoxicity evaluation of amorphous silica nanoparticles of different sizes using the micronucleus and the plasmid lacZ gene mutation assay. Nanotoxicology. 2011;5(2):168–181.
91. Park YH, Kim JN, Jeong SH, et al. Assessment of dermal toxicity of nanosilica using cultured keratinocytes, a human skin equivalent model and an in vivo model. Toxicology. 2010;267(1–3):178–181.
92. Wang F, Gao F, Lan M, Yuan H, Huang Y, Liu J. Oxidative stress contributes to silica nanoparticle-induced cytotoxicity in human embryonic kidney cells. Toxicol In Vitro. 2009;23(5):808–815.
93. Ye Y, Liu J, Xu J, Sun L, Chen M, Lan M. Nano-SiO2 induces apoptosis via activation of p53 and Bax mediated by oxidative stress in human hepatic cell line. Toxicol In Vitro. 2010;24(3):751–758.
94. Ye Y, Liu J, Chen M, Sun L, Lan M. In vitro toxicity of silica nanoparticles in myocardial cells. Environ Toxicol Pharmacol. 2010;29(2): 131–137.
95. Chen Q, Xue Y, Sun J. Kupffer cell-mediated hepatic injury induced by silica nanoparticles in vitro and in vivo. Int J Nanomedicine. 2013;8: 1129–1140.
96. Park Y-H, Bae HC, Jang Y, et al. Effect of the size and surface charge of silica nanoparticles on cutaneous toxicity. Mol Cell Toxicol. 2013;9(1):67–74.
97. Magdolenova Z, Collins A, Kumar A, Dhawan A, Stone V, Dusinska M. Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology. 2014;8:233–278.
98. Geiser M, Rothen-Rutishauser B, Kapp N, et al. Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect. 2005;113(11): 1555–1560.
99. Liu L, Takenaka T, Zinchenlco AA, et al. Cationic silica nanoparticles are efficiently transferred into mammalian cells. Micro-NanoMechatronics and Human Science. International Symposium on MHS ′07. 2007: 281–285.
100. 2 nanometer-sized photocatalysts. Mol Cell Toxicol. 2012;8(2):127–137.
101. 2 nanoparticles during zebrafish embryogenesis development. Mol Cell Toxicol. 2012;8(4):317–326.
102. Nabiev I, Mitchell S, Davies A, et al. Nonfunctionalized nanocrystals can exploit a cell’s active transport machinery delivering them to specific nuclear and cytoplasmic compartments. Nano Lett. 2007;7(11): 3452–3461.
103. Toyokuni S. Oxidative stress and cancer: the role of redox regulation. Biotherapy. 1998;11(2–3):147–154.
104. Rim KT, Kim SJ, Song SW, Park JS. Effect of cerium oxide nanoparticles to inflammation and oxidative DNA damages in H9c2 cells. Mol Cell Toxicol. 2012;8(3):271–280.
105. Zastawny TH, Altman SA, Randers-Eichhorn L, et al. DNA base modifications and membrane damage in cultured mammalian cells treated with iron ions. Free Radic Biol Med. 1995;18(6):1013–1022.
106. Brown DM, Wilson MR, MacNee W, Stone V, Donaldson K. Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines. Toxicol Appl Pharmacol. 2001;175(3):191–199.
107. Knaapen AM, Borm PJ, Albrecht C, Schins RP. Inhaled particles and lung cancer. Part A: mechanisms. Int J Cancer. 2004;109(6): 799–809.
108. Karlsson HL, Cronholm P, Gustafsson J, Moller L. Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol. 2008;21(9): 1726–1732.
109. 2 nanoparticles. Mol Cell Toxicol. 2012;8(4):357–366.
110. 2 nanoparticles in zebrafish embryos. Mol Cell Toxicol. 2013;9(2):129–139.
111. Park EJ, Yi J, Chung KH, Ryu DY, Choi J, Park K. Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. Toxicol Lett. 2008;180(3):222–229.
112. Papageorgiou I, Brown C, Schins R, et al. The effect of nano- and micron-sized particles of cobalt-chromium alloy on human fibroblasts in vitro. Biomaterials. 2007;28(19):2946–2958.
113. Gurr JR, Wang AS, Chen CH, Jan KY. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology. 2005;213(1–2):66–73.
114. Bonvallot V, Baeza-Squiban A, Baulig A, et al. Organic compounds from diesel exhaust particles elicit a proinflammatory response in human airway epithelial cells and induce cytochrome p450 1A1 expression. Am J Respir Cell Mol Biol. 2001;25(4):515–521.
115. Abe S, Takizawa H, Sugawara I, Kudoh S. Diesel exhaust (DE)-induced cytokine expression in human bronchial epithelial cells: a study with a new cell exposure system to freshly generated DE in vitro. Am J Respir Cell Mol Biol. 2000;22(3):296–303.
116. Donaldson K, Tran CL. An introduction to the short-term toxicology of respirable industrial fibres. Mutat Res. 2004;553(1–2):5–9.
117. Waldman WJ, Kristovich R, Knight DA, Dutta PK. Inflammatory properties of iron-containing carbon nanoparticles. Chem Res Toxicol. 2007;20(8):1149–1154.
118. Blanco D, Vicent S, Fraga MF, et al. Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway. Neoplasia. 2007;9(10):840–852.
119. O’Byrne KJ, Dalgleish AG. Chronic immune activation and inflammation as the cause of malignancy. Br J Cancer. 2001;85(4): 473–483.
120. Oberdorster G, Gelein R, Johnston CJ, Mercer P, Corson N, Finkelstein JN. Ambient ultrafine particles: inducers of acute lung injury? In: Mohr U, Dungworth DL, Brain JD, Driscoll KE, Grafstrom RC, Harris CC, editors. Relationships between respiratory disease and exposure to air pollution. Washington: ILSI Press; 1998. pp. 216–229.
121. Li XY, Gilmour PS, Donaldson K, MacNee W. Free radical activity and pro-inflammatory effects of particulate air pollution (PM10) in vivo and in vitro. Thorax. 1996;51(12):1216–1222.
122. Gojova A, Guo B, Kota RS, Rutledge JC, Kennedy IM, Barakat AI. Induction of inflammation in vascular endothelial cells by metal oxide nanoparticles: effect of particle composition. Environ Health Perspect. 2007;115(3):403–409.
123. Peters K, Unger RE, Kirkpatrick CJ, Gatti AM, Monari E. Effects of nano-scaled particles on endothelial cell function in vitro: studies on viability, proliferation and inflammation. J Mater Sci Mater Med. 2004;15(4):321–325.
124. Lane DP. Cancer. p53, guardian of the genome. Nature. 1992; 358(6381):15–16.
125. George S, Pokhrel S, Xia T, et al. Use of a rapid cytotoxicity screening approach to engineer a safer zinc oxide nanoparticle through iron doping. ACS Nano. 2010;4(1):15–29.
126. Fujita K, Morimoto Y, Ogami A, et al. Gene expression profiles in rat lung after inhalation exposure to C60 fullerene particles. Toxicology. 2009;258(1):47–55.
127. Liu X, Sun J. Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-kappaB pathways. Biomaterials. 2010;31(32):8198–8209.
128. Xia T, Kovochich M, Brant J, et al. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett. 2006;6(8): 1794–1807.
129. Mossman BT, Bignon J, Corn M, Seaton A, Gee JB. Asbestos: scientific developments and implications for public policy. Science. 1990;247(4940):294–301.
130. Mossman BT, Churg A. Mechanisms in the pathogenesis of asbestosis and silicosis. Am J Respir Crit Care Med. 1998;157(5 Pt 1): 1666–1680.
131. Robinson BW, Lake RA. Advances in malignant mesothelioma. N Engl J Med. 2005;353(15):1591–1603.
132. Mossman BT, Gee JB. Asbestos-related diseases. N Engl J Med. 1989;320(26):1721–1730.
133. Guthrie GD Jr, Mossman BT. Health effects of mineral dusts. Washington, DC: Mineralogical Society of America; 1993: 28.
134. Heintz NH, Janssen-Heininger YM, Mossman BT. Asbestos, lung cancers, and mesotheliomas: from molecular approaches to targeting tumor survival pathways. Am J Respir Cell Mol Biol. 2010;42(2):133–139.
135. Toyokuni S. Mechanisms of asbestos-induced carcinogenesis. Nagoya J Med Sci. 2009;71(1–2):1–10.
136. Magnani C, Agudo A, Gonzalez CA, et al. Multicentric study on malignant pleural mesothelioma and non-occupational exposure to asbestos. Br J Cancer. 2000;83(1):104–111.
137. Senyigit A, Bayram H, Babayigit C, et al. Malignant pleural mesothelioma caused by environmental exposure to asbestos in the southeast of Turkey: CT findings in 117 patients. Respiration. 2000;67(6): 615–622.
138. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95.
139. Xia T, Li N, Nel AE. Potential health impact of nanoparticles. Annu Rev Public Health. 2009;30:137–150.
140. Luo JC, Hsu KH, Shen WS. Inflammatory responses and oxidative stress from metal fume exposure in automobile welders. J Occup Environ Med. 2009;51(1):95–103.
141. Antonini JM, Stone S, Roberts JR, et al. Effect of short-term stainless steel welding fume inhalation exposure on lung inflammation, injury, and defense responses in rats. Toxicol Appl Pharmacol. 2007;223(3):234–245.
142. Bydash J, Kasmani R, Naraharisetty K. Metal fume-induced diffuse alveolar damage. J Thorac Imaging. 2010;25(2):W27–W29.
143. Cooper RG. Zinc toxicology following particulate inhalation. Indian J Occup Environ Med. 2008;12(1):10–13.
144. Xiao GG, Wang M, Li N, Loo JA, Nel AE. Use of proteomics to demonstrate a hierarchical oxidative stress response to diesel exhaust particle chemicals in a macrophage cell line. J Biol Chem. 2003;278(50): 50781–50790.
145. Wang M, Xiao GG, Li N, Xie Y, Loo JA, Nel AE. Use of a fluorescent phosphoprotein dye to characterize oxidative stress-induced signaling pathway components in macrophage and epithelial cultures exposed to diesel exhaust particle chemicals. Electrophoresis. 2005;26(11):2092–2108.
146. Jung EJ, Avliyakulov NK, Boontheung P, Loo JA, Nel AE. Pro-oxidative DEP chemicals induce heat shock proteins and an unfolding protein response in a bronchial epithelial cell line as determined by DIGE analysis. Proteomics. 2007;7(21):3906–3918.
147. Zhang L, Wang M, Kang X, et al. Oxidative stress and asthma: proteome analysis of chitinase-like proteins and FIZZ1 in lung tissue and bronchoalveolar lavage fluid. J Proteome Res. 2009;8(4):1631–1638.
148. Kang X, Li N, Wang M, et al. Adjuvant effects of ambient particulate matter monitored by proteomics of bronchoalveolar lavage fluid. Proteomics. 2010;10(3):520–531.
149. Li N, Wang M, Bramble LA, et al. The adjuvant effect of ambient particulate matter is closely reflected by the particulate oxidant potential. Environ Health Perspect. 2009;117(7):1116–1123.
150. Li N, Harkema JR, Lewandowski RP, et al. Ambient ultrafine particles provide a strong adjuvant effect in the secondary immune response: implication for traffic-related asthma flares. Am J Physiol Lung Cell Mol Physiol. 2010;299(3):L374–L383.
151. Ohshima H, Tazawa H, Sylla BS, Sawa T. Prevention of human cancer by modulation of chronic inflammatory processes. Mutat Res.2005;591(1–2):110–122.
152. Baggs RB, Ferin J, Oberdorster G. Regression of pulmonary lesions produced by inhaled titanium dioxide in rats. Vet Pathol. 1997;34(6): 592–597.
153. Oberdorster G. Pulmonary effects of inhaled ultrafine particles. Int Arch Occup Environ Health. 2001;74(1):1–8.
154. Wang B, Feng WY, Wang TC, et al. Acute toxicity of nano- and micro-scale zinc powder in healthy adult mice. Toxicol Lett. 2006;161(2): 115–123.
155. Muller J, Huaux F, Fonseca A, et al. Structural defects play a major role in the acute lung toxicity of multiwall carbon nanotubes: toxicological aspects. Chem Res Toxicol. 2008;21(9):1698–1705.
156. Chithrani BD, Chan WC. Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Lett. 2007;7(6):1542–1550.
157. Gratton SE, Ropp PA, Pohlhaus PD, et al. The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci U S A. 2008;105(33):11613–11618.
158. Pacurari M, Yin XJ, Zhao J, et al. Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells. Environ Health Perspect. 2008;116(9):1211–1217.
159. Maples KR, Johnson NF. Fiber-induced hydroxyl radical formation: correlation with mesothelioma induction in rats and humans. Carcinogenesis. 1992;13(11):2035–2039.
160. Donaldson K, Beswick PH, Gilmour PS. Free radical activity associated with the surface of particles: a unifying factor in determining biological activity? Toxicol Lett. 1996;88(1–3):293–298.
161. Ghio AJ, Stonehuerner J, Dailey LA, Carter JD. Metals associated with both the water-soluble and insoluble fractions of an ambient air pollution particle catalyze an oxidative stress. Inhal Toxicol. 1999;11(1):37–49.
162. Kagan VE, Tyurina YY, Tyurin VA, et al. Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron. Toxicol Lett. 2006;165(1):88–100.
163. Lam CW, James JT, McCluskey R, Hunter RL. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci. 2004;77(1):126–134.
164. Wick P, Manser P, Limbach LK, et al. The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol Lett. 2007;168(2): 121–131.
165. Fubini B, Ghiazza M, Fenoglio I. Physico-chemical features of engineered nanoparticles relevant to their toxicity. Nanotoxicology. 2010;4(4):347–363.
166. Maynard AD, Baron PA, Foley M, Shvedova AA, Kisin ER, Castranova V. Exposure to carbon nanotube material: aerosol release during the handling of unrefined single-walled carbon nanotube material. J Toxicol Environ Health A. 2004;67(1):87–107.
167. Shvedova AA, Kisin ER, Mercer R, et al. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol. 2005;289(5):L698–L708.
168. Thess A, Lee R, Nikolaev P, et al. Crystalline ropes of metallic carbon nanotubes. Science. 1996;273(5274):483–487.
169. Kim YH, Park HW, Ryoo ZY, Lee HS, Kim DH, Lee S. Abnormal effects of unpurified and purified multi-walled carbon nanotubes in A549, Jurkat and THP-1 cell lines. Mol Cell Toxicol. 2012;8(1): 103–112.
170. Chandra S, Barick KC, Bahadur D. Oxide and hybrid nanostructures for therapeutic applications. Adv Drug Deliv Rev. 2011;63(14–15): 1267–1281.
171. Magdolenova Z, Bilanicova D, Pojana G, et al. Impact of agglomeration and different dispersions of titanium dioxide nanoparticles on the human related in vitro cytotoxicity and genotoxicity. J Environ Monit. 2012;14(2):455–464.
172. Fu YS, Du XW, Kulinich SA, et al. Stable aqueous dispersion of ZnO quantum dots with strong blue emission via simple solution route. J Am Chem Soc. 2007;129(51):16029–16033.
173. Munnier E, Cohen-Jonathan S, Linassier C, et al. Novel method of doxorubicin-SPION reversible association for magnetic drug targeting. Int J Pharm. 2008;363(1–2):170–176.
174. Valois CR, Braz JM, Nunes ES, et al. The effect of DMSA-functionalized magnetic nanoparticles on transendothelial migration of monocytes in the murine lung via a beta2 integrin-dependent pathway. Biomaterials. 2010;31(2):366–374.
175. Maurizi L, Bisht H, Bouyer F, Millot N. Easy route to functionalize iron oxide nanoparticles via long-term stable thiol groups. Langmuir. 2009;25(16):8857–8859.
176. Lim JK, Majetich SA, Tilton RD. Stabilization of superparamagnetic iron oxide core-gold shell nanoparticles in high ionic strength media. Langmuir. 2009;25(23):13384–13393.
177. Xie J, Xu C, Kohelr N, Hou Y, Sun S. Controlled PEGylation of monodisperse Fe3O4 nanoparticles for reduced non-specific uptake by macrophage cells. Adv Mater. 2007;19(20):3163–3166.
178. Soenen SJH, Hodenius M, Schmitz-Rode T, De Cuyper M. Protein-stabilized magnetic fluids. J Magn Magn Mater. 2008; 320(5):634–641.
179. Nasongkla N, Bey E, Ren J, et al. Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett. 2006;6(11):2427–2430.
180. Pradhan P, Giri J, Rieken F, et al. Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy. J Control Release. 2010;142(1):108–121.
181. Sayes CM, Liang F, Hudson JL, et al. Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro. Toxicol Lett. 2006;161(2):135–142.
182. Singh R, Pantarotto D, Lacerda L, et al. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc Natl Acad Sci U S A. 2006;103(9): 3357–3362.
183. Chen P, Kuo CW, Lai JJL. Cytotoxicity of the functionalized gold and silver nanorods. Mat Res Soc. 2007;951:105–110.
184. Yim WC, Lee B-M, Kwon Y. Cross-experimental analysis of microarray gene expression datasets for in silico risk assessment of TiO2 nano-particles. Mol Cell Toxicol. 2012;8(3):229–239.
185. Park S-K, Kim J-J, Yu A-R, Lee M-Y, Park S-K. Electrolyzed-reduced water confers increased resistance to environmental stresses. Mol Cell Toxicol. 2012;8(3):241–247.
186. Jiang J, Oberdörster G, Biswas P. Characterisation of size, surface charge and agglomeration state of nanoparticle dispersions for toxicological studies. J Nanopart Res. 2009;11:77–89.
187. Harush-Frenkel O, Debotton N, Benita S, Altschuler Y. Targeting of nanoparticles to the clathrin-mediated endocytic pathway. Biochem Biophys Res Commun. 2007;353(1):26–32.
188. Lockman PR, Koziara JM, Mumper RJ, Allen DD. Nanoparticle surface charges alter blood-brain barrier integrity and permeability. J Drug Target. 2004;12(9–10):635–641.
189. Nan A, Bai X, Son SJ, Lee SB, Ghandehari H. Cellular uptake and cytotoxicity of silica nanotubes. Nano Lett. 2008;8(8):2150–2154.
190. Clift MJ, Rothen-Rutishauser B, Brown DM, et al. The impact of different nanoparticle surface chemistry and size on uptake and toxicity in a murine macrophage cell line. Toxicol Appl Pharmacol. 2008;232(3):418–427.
191. Gonzalez L, Lison D, Kirsch-Volders M. Genotoxicity of engineered nanomaterials:a critical review. Nanotoxicology. 2008;2:252–273.
192. Landsiedel R, Kapp MD, Schulz M, Wiench K, Oesch F. Gentoxicity investigations on nanomaterials: methods, preparation and characterization of test material, potential artifacts and limitations- many questions, some answers. Mutat Res. 2009;681:241–258.