Genotoxicity and Epigenetic Modifications in Response to Atmospheric and Engineered Nanoparticles


Nanoparticles are of increasing interest and concern as they become more widely used in consumer products, industry and medicine. Nanoparticles differ from their ‘bulk’ materials in physiochemical properties, creating interest and further applications. In addition to being engineered, humans are constantly exposed to nanoparticles (NPs) through ambient air pollution. There is a need for toxicological assessment of these particles as humans come into contact with them every day. The toxicological mechanism and biological fate of these particles are not well known. Findings in the fields of genotoxicity and epigenetics shed light on potential mechanisms for adverse human health effects when exposed to these particles. There is still much work to be done in order to properly assess the risk of NP exposure.

Key Concepts:

  • Nanoparticles have different inherent physiochemical properties from bulk materials of the same composition.

  • Studies show that nanoparticles at smaller dimensions induce stronger toxic effects than the same particles at larger dimensions

  • Oxidative stress is increased when exposed to nanoparticles, more free radicals will cause more cellular and DNA damage.

  • Nanoparticles are being investigated for use in clinical settings, specifically diagnostic procedures and drug delivery.

  • Epigenetic modifications are those in which there is no genetic mutation or DNA damage present.

  • Nanoparticles will be constituents of ambient particulate matter, therefore, all life is exposed to varying amounts of nanoparticles daily.

  • Government organisations are working to increase research and development involving nanoparticles in order to better understand their mechanisms of action.

Keywords: particulate matter; nanoparticles; epigenetics; DNA methylation; histone modifications; genotoxicity; oxidative stress; in vitro; in vivo


Arita A and Costa M (2009) Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium. Metallomics 1(3): 222.

Asare N, Instanes C, Sandberg WJ et al. (2012) Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicology 291(1–3): 65–72.

Beer C, Foldbjerg R, Hayashi Y, Sutherland DS and Autrup H (2012) Toxicity of silver nanoparticles – nanoparticle or silver ion? Toxicology Letters 208(3): 286–292.

Bhattacharyya SN, Habermacher R, Martine U, Closs EI and Filipowicz W (2006) Relief of microRNA‐mediated translational repression in human cells subjected to stress. Cell 125(6): 1111–1124.

Cantone L, Nordio F, Hou L et al. (2011) Inhalable metal‐rich air particles and histone H3K4 dimethylation and H3K9 acetylation in a cross‐sectional study of steel workers. Environmental Health Perspectives 119(7): 964–969.

Capstick TGD and Clifton IJ (2012) Inhaler technique and training in people with chronic obstructive pulmonary disease and asthma: effects of particle size on lung deposition. Expert Reviews Respiratory Medicine 6(1): 91–103.

Cheng‐Teng NG, Dheen ST, Yip W‐CG et al. (2011) The induction of epigenetic regulation of PROS1 gene in lung fibroblasts by gold nanoparticles and implications for potential lung injury. Biomaterials 32(30): 7609–7615.

Choi AO, Brown SE, Szyf M and Maysinger D (2008) Quantum dot‐induced epigenetic and genotoxic changes in human breast cancer cells. Journal of Molecular Medicine 86(3): 291–302.

Conroy J, Byrne SJ, Gun'ko YK et al. (2008) CdTe nanoparticles display tropism to core histones and histone‐rich cell organelles. Small 4(11): 2006–2015.

Costa M and Yao Y (2013) Genetic and epigenetic effects of nanoparticles. Journal of Molecular and Genetic Medicine 7(4): 1–6.

Donaldson K and Warheit DB (2011) From ambient ultrafine particles to nanotechnology and nanotoxicology. In: Cassee FR, Mills NL and Newby D (eds) Cardiovascular Effects of Inhaled Ultrafine and Nanosized Particles, pp. 525–543. Hoboken, NJ: John Wiley.

Friedberg EC, Walker GC and Siede W (1995) Chap. 1–3 DNA Repair and Mutagenesis, 2nd edn. Washington, DC: ASM.

Geiser M, Rothen-Rutishauser B, Kapp N et al. (2005) Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environmental Health Perspectives 113 (11): 1555–1560.

Gong C, Tao G, Yang L et al. (2010) SiO2 nanoparticles induce global genomic hypomethylation in HaCaT cells. Biochemical and Biophysical Research Communications 397(3): 397–400.

Gong C, Tao G, Yang L et al. (2012) Methylation of PARP‐1 promoter involved in the regulation of nano‐SiO2‐induced decrease of PARP‐1 MRNA expression. Toxicology Letters 209(3): 264–269.

Huehn J, Polansky JK and Hamann A (2009) Epigenetic control of FOXP3 expression: the key to a stable regulatory T‐cell ineage? Nature Reviews Immunology 9(2): 83–89.

Ju L, Zhang G, Zhang C et al. (2013) Quantum dot‐related genotoxicity perturbation can be attenuated by PEG encapsulation. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 753(1): 54–64.

Karlsson HL, Gustafsson J, Cronholm P and Möller L (2009) Size‐dependent toxicity of metal oxide particles – a comparison between nano‐ and micrometer size. Toxicology Letters 188(2): 112–118.

Lee M‐W, Chen M‐L, Candice Lung S‐C et al. (2010) Exposure assessment of PM2.5 and urinary 8‐OHdG for diesel exhaust emission inspector. Science of the Total Environment 408(3): 505–510.

Li N, Sioutas C, Cho A et al. (2003) Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environmental Health Perspectives 111 (4): 455–460.

Li Y, Chen DH, Yan J et al. (2012) Genotoxicity of silver nanoparticles evaluated using the ames test and in vitro micronucleus assay. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 745(1–2): 4–10.

Nadeau K, Mcdonald‐Hyman C, Noth EM et al. (2010) Ambient air pollution impairs regulatory T‐cell function in asthma. Journal of Allergy and Clinical Immunology 126(4): 845–852.e10.

Nel A, Xia T, Mädler L and Li N (2006) Toxic potential of materials at the nanolevel. Science 311: 622–627.

Oberdorster G, Oberdorster E and Oberdorster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives 113: 823–839.

Paino IMM, Marangoni VS, De Cássia Silva De Oliveira R, Antunes LMG and Zucolotto V (2012) Cyto and genotoxicity of gold nanoparticles in human hepatocellular carcinoma and peripheral blood mononuclear cells. Toxicology Letters 215(2): 119–125.

Park MVDZ, Neigh AM, Vermeulen JP et al. (2011) The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles. Biomaterials 32(36): 9810–9817.

Pathakoti K, Hwang H‐M, Xu H, Aguilar ZP and Wang A (2013) In vitro cytotoxicity of CdSe/ZnS quantum dots with different surface coatings to human keratinocytes HaCaT cells. Journal of Environmental Sciences 25(1): 163–171.

Piao MJ, Kang KA, Lee IK et al. (2011) Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria‐involved apoptosis. Toxicology Letters 201(1): 92–100.

Powers KW (2005) Research strategies for safety evaluation of nanomaterials. Part VI. Characterization of nanoscale particles for toxicological evaluation. Toxicological Sciences 90(2): 296–303.

Risom L, Møller P and Loft S (2005) Oxidative stress‐induced DNA damage by particulate air pollution. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 592(1–2): 119–137.

Sanvicens N and Marco MP (2008) Multifunctional nanoparticles – properties and prospects for their use in human medicine. Trends in Biotechnology 26(8): 425–433.

Sawant RM, Hurley JP, Salmaso S et al. (2006) “SMART” drug delivery systems: double‐targeted PH‐responsive pharmaceutical nanocarriers. Bioconjugate Chemistry 17(4): 943–949.

Schulz M, Ma‐Hock L, Brill S et al. (2012) Investigation on the genotoxicity of different sizes of gold nanoparticles administered to the lungs of rats. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 745(1–2): 51–57.

Stoccoro A, Karlsson HL, Coppedè F and Migliore L (2013) Epigenetic effects of nano‐sized materials. Toxicology 313(1): 3–14.

Sykes EA, Dai Q, Tsoi KM, Hwang DM and Chan CW (2014) Nanoparticle exposure in animals can be visualized in the skin and analysed via skin biopsy. Nature Communications 13(5): 3796.

UK Department for Environment, Food and Rural Affairs, Nobel House (2007) Characterising the Potential Risks Posed by Engineered Nanoparticles: A Second UK Government Research Report.

United States Government with National Nanotechnology Initiative (2000) USA NNI Page.

Vogel U, Catalan J, Lindberg H et al. (2014) Chapter 3: nanomaterials and human health. In: Harri A (ed.) Handbook of Nanosafety: Measurement, Exposure and Toxicology. San Diego, CA: Elsevier Academic.

Winnik FM and Maysinger D (2013) Quantum dot cytotoxicity and ways to reduce it. Accounts of Chemical Research 46(3): 672–680.

Yauk C, Polyzos A, Rowan‐Carroll A et al. (2008) Germ‐line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location. Proceedings of the National Academy of Sciences 105(2): 605–610.

Further Reading

Balansky R, Longobardi M, Ganchev G et al. (2013) Transplacental clastogenic and epigenetic effects of gold nanoparticles in mice. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 751–752: 42–48.

Coradeghini R, Gioria S, García CP et al. (2013) Size‐dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts. Toxicology Letters 217(3): 205–216.

EPA (2005) Since 2005a peer reviewed paper, cited by 1058, has remarked that silver nanoparticles are a bactericide and that this property is “only” size dependent.

Hull M and Bowman D (2010) Nanotechnology, Environmental Health and Safety: Risks, Regulation and Management. Amsterdam: Elsevier/WA.

Munoz A and Costa M (2012) Elucidating the mechanisms of nickel compound uptake: A review of particulate and nano‐nickel endocytosis and toxicity. Toxicology and Applied Pharmacology 260(1): 1–16.

Ryman-Rasmussen JP, Riviere JE and Monteir-Riviere NA (2006) Penetration of intact skin by quantum dots with diverse physicochemical properties. Toxicological Sciences 91(1): 159–165.

Sato F, Tsuchiya S, Meltzer SJ and Shimizu K (2011) MicroRNAs and epigenetics. FEBS Journal 278(10): 1598–1609.

Wang H, Wu F, Meng W et al. (2013) Engineered nanoparticles may induce genotoxicity. Environmental Science & Technology 47(23): 13212–13214.

Xia T, Kovochich M, Brant J et al. (2006) Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Letters 6: 1794–1807.

Zook JM, Maccuspie RI, Locascio LE, Halter MD and Elliott JT (2011) Stable nanoparticle aggregates/agglomerates of different sizes and the effect of their size on hemolytic cytotoxicity. Nanotoxicology 5(4): 517–530.

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Des Marais, Thomas L, and Costa, Max(Oct 2014) Genotoxicity and Epigenetic Modifications in Response to Atmospheric and Engineered Nanoparticles. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0025833]