1Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran
2Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
ZnO NPs (zinc oxide nanoparticles) has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species) production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.
 Nair S, Sasidharan A, Rani VD, Menon D, Nair S, Manzoor K, et al. Role of size scale of ZnO nanoparticles and microparticles on toxicity toward bacteria and osteoblast cancer cells. J. Mater. Sci. Mater. Med. 2009; 20(1): 235-41.
 De Berardis B, Civitelli G, Condello M, Lista P, Pozzi R, Arancia G, et al. Exposure to ZnO nanoparticles induces oxidative stress and cytotoxicity in human colon carcinoma cells. J. Mater. Sci. Mater. Med.Toxicology and applied pharmacology. 2010; 246(3): 116-27.
 Deng X, Luan Q, Chen W, Wang Y, Wu M, Zhang H, et al. Nanosized zinc oxide particles induce neural stem cell apoptosis. Nanotechnology. 2009; 20(11): 115101.
 Huang C-C, Aronstam RS, Chen D-R, Huang Y-W. Oxidative stress, calcium homeostasis, and altered gene expression in human lung epithelial cells exposed to ZnO nanoparticles. Toxicol. in Vitro. 2010; 24(1): 45-55.
 Premanathan M, Karthikeyan K, Jeyasubramanian K, Manivannan G. Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. Nanomedicine: NBM Nanomedicine. 2011; 7(2): 184-92.
 Hanley C, Layne J, Punnoose A, Reddy K, Coombs I, Coombs A, et al. Preferential killing of cancer cells andactivated human T cells using ZnO nanoparticles. Nanotechnology. 2008; 19(29): 295103.
 Wang H, Wingett D, Engelhard MH, Feris K, Reddy K, Turner P, et al. Fluorescent dye encapsulated ZnO particles with cell-specific toxicity for potential use in biomedical applications. J. Mater. Sci. Mater. Med. 2009; 20(1): 11-22.
 Ostrovsky S, Kazimirsky G, Gedanken A, Brodie C. Selective cytotoxic effect of ZnO nanoparticles on glioma cells. Nano Res. 2009; 2(11): 882-90.
 Akhtar MJ, Ahamed M, Kumar S, Khan MM, Ahmad J, Alrokayan SA. Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species. Int. J. Nanomed. 2012; 7: 845.
 Ahamed M, Akhtar M, Raja M, Ahmad I, Siddiqui M, AlSalhi M, et al. Zinc oxide nanorod induced apoptosis via p53, bax/bcl-2 and survivin pathways in human lung cancer cells: role of oxidative stress. Nanomedicine: NBM. 2011; 7: 904-13.
 Rasmussen JW, Martinez E, Louka P, Wingett DG. Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications. Expert Opin. Drug Deliv. 2010; 7(9): 1063-77.
 Zhang H, Shan Y, Dong L. A comparison of TiO2 and ZnO nanoparticles as photosensitizers in photodynamic therapy for cancer. J. Biomed. Nanotechnol. 2014; 10(8): 1450-7.
 Goharshadi EK, Abareshi M, Mehrkhah R, Samiee S, Moosavi M, Youssefi A, et al. Preparation, structural characterization, semiconductor and photoluminescent properties of zinc oxide nanoparticles in a phosphonium-based ionic liquid. Mat. Sci. Semicon. Proc. 2011; 14(1): 69-72.
 Goharshadi EK, Ding Y, Jorabchi MN, Nancarrow P. Ultrasound-assisted green synthesis of nanocrystalline ZnO in the ionic liquid [hmim][NTf 2]. Ultrason. Sonochem. 2009; 16(1): 120-3.
 Goharshadi EK, Ding Y, Nancarrow P. Green synthesis of ZnO nanoparticles in a room-temperature ionic liquid 1-ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide. J. Phys. Chem. Solids. 2008; 69(8): 2057-60.
 Jalal R, Goharshadi EK, Abareshi M, Moosavi M, Yousefi A, Nancarrow P. ZnO nanofluids: green synthesis, characterization, and antibacterial activity. Mater. Chem. Phys. 2010; 121(1): 198-201.
 Moosavi M, Goharshadi EK, Youssefi A. Fabrication, characterization, and measurement of some physicochemical properties of ZnO nanofluids. Int. J. Heat Fluid. 2010; 31(4): 599-605.
 AshaRani P, Low Kah Mun G, Hande MP, Valiyaveettil S. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano. 2008; 3(2): 279-90.
 Nel A, Xia T, Mädler L, Li N. Toxic potential of materials at the nanolevel. Science. 2006; 311(5761): 622-7.
 Xia T, Kovochich M, Liong M, Madler L, Gilbert B, Shi H, 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): 2121-34.
 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): 211-8.
 Singh N, Manshian B, Jenkins GJ, Griffiths SM, Williams PM, Maffeis TG, et al. NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials. 2009; 30(23): 3891-914.
 Xia T, Kovochich M, Brant J, Hotze M, Sempf J, Oberley T, 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): 1794-807.
 Gong KW, Zhao W, Li N, Barajas B, Kleinman M, Sioutas C, et al. Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells. Genome Biol. 2007; 8(7): R149.
 Darroudi M, Sabouri Z, Kazemi Oskuee R, Kargar H, Hosseini HA. Neuronal toxicity of biopolymer-template synthesized ZnO nanoparticles. NMJ. 2013;1(2): 88-93.
 Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Hlth. Perspect. 2005: 823-39.
 Manke A, Wang L, Rojanasakul Y. Mechanisms of nanoparticle-induced oxidative stress and toxicity. BioMed Res. Int. 2013; 2013.
 Hsiao I-L, Huang Y-J. Effects of various physicochemical characteristics on the toxicities of ZnO and TiO 2 nanoparticles toward human lung epithelial cells. Sci. Total Environ. 2011; 409(7): 1219-28.
 Lin W, Xu Y, Huang C-C, Ma Y, Shannon KB, Chen D-R, et al. Toxicity of nano-and micro-sized ZnO particles in human lung epithelial cells. J. Nanopart. Res. 2009; 11(1): 25-39.
 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.
 Zhu X, Wang J, Zhang X, Chang Y, Chen Y. The impact of ZnO nanoparticle aggregates on the embryonic development of zebrafish (Danio rerio). Nanotechnology. 2009; 20(19): 195103.
 Moos PJ, Chung K, Woessner D, Honeggar M, Cutler NS, Veranth JM. ZnO particulate matter requires cell contact for toxicity in human colon cancer cells. Chem. Res. Toxicol Chemical research in toxicology. 2010; 23(4): 733-9.
 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): 852-70.
 Park SJ, Park YC, Lee SW, Jeong MS, Yu K-N, Jung H, et al. Comparing the toxic mechanism of synthesized zinc oxide nanomaterials by physicochemical characterization and reactive oxygen species properties. Toxicol. Lett. 2011; 207(3): 197-203.
 Valdiglesias V, Costa C, Kiliç G, Costa S, Pásaro E, Laffon B, et al. Neuronal cytotoxicity and genotoxicity induced by zinc oxide nanoparticles. . Environ. Int. 2013; 55: 92-100.
 Kim YH, Fazlollahi F, Kennedy IM, Yacobi NR, Hamm-Alvarez SF, Borok Z, et al. Alveolar epithelial cell injurydue to zinc oxide nanoparticle exposure. Am. J. Respir. Crit. Care. Med. 2010; 182(11): 1398-409.
 Sahu D, Kannan G, Vijayaraghavan R, Anand T, Khanum F. Nanosized zinc oxide induces toxicity in human lung cells. ISRN toxicology. 2013; 2013.
 Yu K-N, Yoon T-J, Minai-Tehrani A, Kim J-E, Park SJ, Jeong MS, et al. Zinc oxide nanoparticle induced autophagic cell death and mitochondrial damage via reactive oxygen species generation. Toxicol. in Vitro. 2013; 27(4): 1187-95.
 Guan R, Kang T, Lu F, Zhang Z, Shen H, Liu M. Cytotoxicity, oxidative stress, and genotoxicity in human hepatocyte and embryonic kidney cells exposed to ZnO nanoparticles. Nanoscale Res. Lett. 2012; 7(1): 1-7.
 Alarifi S, Ali D, Alkahtani S, Verma A, Ahamed M, Ahmed M, 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. Nanomed. 2013; 8:983.
 Yin Y, Lin Q, Sun H, Chen D, Wu Q, Chen X, et al. Cytotoxic effects of ZnO hierarchical architectures on RSC96 Schwann cells. Nanoscale Res. Lett. 2012; 7(1): 1-8.
 Li N, Xia T, Nel AE. The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radical Bio. Med. 2008; 44(9): 1689-99.
 Yang Z, Xie C. Zn 2+ release from zinc and zinc oxide particles in simulated uterine solution. Colloids Surf B Biointerfaces. 2006; 47(2): 140-5.
 Knaapen AM, Borm PJ, Albrecht C, Schins RP. Inhaled particles and lung cancer. Part A: Mechanisms. Int. J. Cancer. 2004; 109(6): 799-809.
 Donaldson K, Brown D, Clouter A, Duffin R, MacNee W, Renwick L, et al. The pulmonary toxicology of ultrafine particles. J. Aerosol Med. 2002; 15(2): 213-20.
 Ma H, Williams PL, Diamond SA. Ecotoxicity of manufactured ZnO nanoparticles–a review. A review. Environ. Pollut. 2013;172:76-85.
 Boonstra J, Post JA. Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells. Gene. 2004; 337: 1-13.
 Zabirnyk O, Yezhelyev M, Seleverstov O. Nanoparticles as a novel class of autophagy activators. Autophagy. 2007; 3(3): 278-81.
 Yu L, Lu Y, Man N, Yu SH, Wen LP. Rare earth oxide nanocrystals induce autophagy in HeLa cells. Small. 2009; 5(24): 2784-7.
 Chen Y, Yang L, Feng C, Wen L-P. Nano neodymium oxide induces massive vacuolization and autophagic cell death in non-small cell lung cancer NCI-H460 cells. Biochem. Biophys. Res. 2005; 337(1): 52-60.
 Lanone S, Boczkowski J. Biomedical applications and potential health risks of nanomaterials: molecular mechanisms. Curr. Mol. Med. 2006; 6(6): 651-63.
 Hubbard AK, Timblin CR, Shukla A, Rincón M, Mossman BT. Activation of NF-κB-dependent gene expression by silica in lungs of luciferase reporter mice. Am. J. Physiol. Lung Cell Mol. Physiol. 2002; 282(5): L968-L75.
 Murray AR, Kisin ER, Tkach AV, Yanamala N, Mercer R, Young S-H, et al. Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos. Part Fibre Toxicol. 2012;9(10):1-19.
 Pujalté I, Passagne I, Brouillaud B, Tréguer M, Durand E, Ohayon-Courtès C, et al. Cytotoxicity and oxidative stress induced by different metallic nanoparticles on human kidney cells. Part Fibre Toxicol. 2011;8(10):1-16.
 Jeng HA, Swanson J. Toxicity of metal oxide nanoparticles in mammalian cells. J. Environ. Sci. Health. 2006;41(12):2699-711.
 Song W, Zhang J, Guo J, Zhang J, Ding F, Li L, et al. Role of the dissolved zinc ion and reactive oxygen species in cytotoxicity of ZnO nanoparticles. Toxicol. Lett. 2010;199(3):389-97.
 Syama S, Sreekanth P, Varma H, Mohanan P. Zinc oxide nanoparticles induced oxidative stress in mouse bone marrow mesenchymal stem cells. Toxicol. Mech. Methods. 2014;24(9):644-53.
 Fukui H, Horie M, Endoh S, Kato H, Fujita K, Nishio K, et al. Association of zinc ion release and oxidative stress induced by intratracheal instillation of ZnO nanoparticles to rat lung. Chem. Biol. Interact. 2012;198(1):29-37.
 Nel AE, Mädler L, Velegol D, Xia T, Hoek EM, Somasundaran P, et al. Understanding biophysicochemical interactions at the nano–bio interface. Nat. Mater. 2009; 8(7): 543-57.
 Brown AM, Kristal BS, Effron MS, Shestopalov AI, Ullucci PA, Sheu K-FR, et al. Zn2+ inhibits α-ketoglutarate-stimulated mitochondrial respiration and the isolated α-ketoglutarate dehydrogenase complex. J. Biol. Chem. 2000; 275(18): 13441-7.
 Frazzini V, Rockabrand E, Mocchegiani E, Sensi S. Oxidative stress and brain aging: is zinc the link? Biogerontology. 2006; 7(5-6): 307-14.
 Wiseman DA, Wells SM, Hubbard M, Welker JE, Black SM. Alterations in zinc homeostasis underlie endothelial cell death induced by oxidative stress from acute exposure to hydrogen peroxide. Am. J. Physiol. Lung Cell Mol. Physiol. 2007; 292(1): L165-L77.
 Wiseman DA, Wells SM, Wilham J, Hubbard M, Welker JE, Black SM. Endothelial response to stress from exogenous Zn2+ resembles that of NO-mediated nitrosative stress, and is protected by MT-1 overexpression. Am. J. Physiol. Cell Physiol. 2006; 291(3): C555-C68.
 Martinez GR, Loureiro APM, Marques SA, Miyamoto S, Yamaguchi LF, Onuki J, et al. Oxidative and alkylating damage in DNA. Mutat. Res. 2003; 544(2): 115-27.
 Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 2007; 39(1): 44-84.
 Toyokuni S. Oxidative stress and cancer: the role of redox regulation. Biotherapy. 1998; 11(2-3): 147-54.
 Marnett LJ. Oxy radicals, lipid peroxidation and DNA damage. Toxicology. 2002; 181: 219-22.
 Niedernhofer LJ, Daniels JS, Rouzer CA, Greene RE, Marnett LJ. Malondialdehyde, a product of lipid peroxidation, is mutagenic in human cells. J. Biol. Chem. 2003; 278(33): 31426-33.
 Zhao X, Wang S, Wu Y, You H, Lv L. Acute ZnO nanoparticles exposure induces developmental toxicity, oxidative stress and DNA damage in embryo-larval zebrafish. Aquat. Toxicol. 2013;136: 49-59.
 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. Environmental health perspectives. 2007: 403-9.
 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): 321-5.
 Jaiswal M, LaRusso NF, Burgart LJ, Gores GJ. Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res. 2000; 60(1): 184-90.
 Valinluck V, Sowers LC. Inflammation-mediated cytosine damage: a mechanistic link between inflammation and the epigenetic alterations in human cancers. Cancer Res. 2007; 67(12): 5583-6.
 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): 215-24.
 Gopalan RC, Osman IF, Amani A, De 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): 33-9.
 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. Gen-Tox. En. 2012; 745(1): 84-91.
 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): 1726-32.
 Chen M, von Mikecz A. Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO 2 nanoparticles. Exp. Cell Res. 2005; 305(1): 51-62.
 Shukla RK, Sharma V, Pandey AK, Singh S, Sultana S, Dhawan A. ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells. Toxicol. In Vitro. 2011; 25(1): 231-41.
 Min K-S. [Physiological significance of metallothionein in oxidative stress. Yakugaku Zasshi. 2007; 127(4): 695-702.
 Griffitt RJ, Weil R, Hyndman KA, Denslow ND, Powers K, Taylor D, et al. Exposure to copper nanoparticles causes gill injury and acute lethality in zebrafish (Danio rerio). Environ. Sci. Technol. 2007; 41(23): 8178-86.
 Bishop GM, Dringen R, Robinson SR. Zinc stimulates the production of toxic reactive oxygen species (ROS) and inhibits glutathione reductase in astrocytes. Free Radic. Biol. Med. 2007; 42(8): 1222-30.
 Horie M, Nishio K, Fujita K, Endoh S, Miyauchi A, Saito Y, et al. Protein adsorption of ultrafine metal oxide and its influence on cytotoxicity toward cultured cells. Chem. Res. Toxicol. 2009; 22(3): 543-53.
 Stone V, Tuinman M, Vamvakopoulos J, Shaw J, Brown D, Petterson S, et al. Increased calcium influx in a monocytic cell line on exposure to ultrafine carbon black. . Eur. Respir. J. 2000;15(2): 297-303.
 Moller W, Brown DM, Kreyling L, Stone V. Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium. Part. Fibre Toxicol. 2005; 2(1): 7.
 Wang L, Bowman L, Lu Y, Rojanasakul Y, Mercer RR, Castranova V, et al. Essential role of p53 in silica-induced apoptosis. Am. J. Physiol. Lung Cell Mol. Physiol. 2005; 288(3): L488-L96.
 Harrison R. Structure and function of xanthine oxidoreductase: where are we now? Free Radical Bio. Med. 2002; 33(6): 774-97.
 Dong Z, Saikumar P, Weinberg JM, Venkatachalam MA. Calcium in cell injury and death. Annu. Rev. Pathol. 2006;1: 405-34.
 Rizzuto R, Giorgi C, Romagnoli A, Pinton P. Ca2+ signaling, mitochondria and cell death. Curr. Mol. Med. 2008; 8(2): 119-30.
 Brown JL. Zinc fume fever. Br. J. Radiol. 1988; 61(724): 327-9.
 Jeong SH, Kim HJ, Ryu HJ, Ryu WI, Park Y-H, Bae HC, et al. ZnO nanoparticles induce TNF-α expression via ROS-ERK-Egr-1 pathway in human keratinocytes. J Dermatol Sci. 2013; 72(3): 263-73.
 Xiong D, Fang T, Yu L, Sima X, Zhu W. Effects of nano-scale TiO 2, ZnO and their bulk counterparts on zebrafish: acute toxicity, oxidative stress and oxidative damage. Sci. Total Environ. 2011; 409(8):1444-52.
 Lipovsky A, Nitzan Y, Gedanken A, Lubart R. Antifungal activity of ZnO nanoparticles—the role of ROS mediated cell injury. Nanotechnology. 2011; 22(10): 105101.
 Manna P, Ghosh M, Ghosh J, Das J, Sil PC. Contribution of nano-copper particles to in vivo liver dysfunction and cellular damage: Role of IκBα/NF-κB, MAPKs and mitochondrial signal. Nanotoxicology. 2012; 6(1): 1-21.
 Shi Y, Wang F, He J, Yadav S, Wang H. Titanium dioxide nanoparticles cause apoptosis in BEAS-2B cells through the caspase 8/t-Bid-independent mitochondrial pathway. Toxicol. Lett Toxicology letters. 2010; 196(1): 21-7.
 Li Y, Xu Y, Ling M, Yang Y, Wang S, Li Z, et al. mot-2–Mediated Cross Talk between Nuclear Factor-κB and p53 Is Involved in Arsenite-Induced Tumorigenesis of Human Embryo Lung Fibroblast Cells. Environ. Health Perspect. 2010: 936-42.
 Wang J, Deng X, Zhang F, Chen D, Ding W. ZnO nanoparticle-induced oxidative stress triggers apoptosis by activating JNK signaling pathway in cultured primary astrocytes. Nanoscale Res. Lett. 2014; 9(1): 1-12.
 Franklin NM, Rogers NJ, Apte SC, Batley GE, Gadd GE, Casey PS. Comparative toxicity of nanoparticulate ZnO, bulk ZnO, and ZnCl2 to a freshwater microalga (Pseudokirchneriella subcapitata): the importance of particle solubility. Environ. Sci. Technol. 2007; 41(24): 8484-90.
 Moreau JW, Weber PK, Martin MC, Gilbert B, Hutcheon ID, Banfield JF. Extracellular proteins limit the dispersal of biogenic nanoparticles. Science. 2007; 316(5831): 1600-3.
 Talalay P, Dinkova-Kostova AT, Holtzclaw WD. Importance of phase 2 gene regulation in protection against electrophile and reactive oxygen toxicity and carcinogenesis. Adv. Enzyme Regul. 2003; 43(1): 121-34.