Abstract
The aim of this chapter is to present some of the principal methodologies used to study the effects of toxic substances on DNA, which can be used to analyze aspects of nanomaterial toxicity. It is not the intention here to undertake an in-depth survey of the topic, but rather to highlight the techniques that can be used in nanotoxicity studies. The available methods for evaluating effects on DNA include genotoxicity tests such as (1) the Allium cepa chromosome aberration test, (2) the comet analysis, (3) the micronucleus test, and (4) the cytogenetic analysis. In addition, this chapter also described the methodologies for analysis of gene expression that can be applied to the effects of nanomaterials. A description of the characteristics of each method is provided, together with results of selected studies that have evaluated the effects of nanomaterials, and a critical discussion of the main advantages and disadvantages of each technique. The chapter also highlights the challenges and future perspectives for studies of the effects of nanostructured materials on DNA.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Abdul Khaliq R, Kafafy R, Salleh HM et al (2012) Enhancing the efficiency of polymerase chain reaction using graphene nanoflakes. Nanotechnology 23:455106
Akhmedov AT, Frei C, Tsai-Pflugfelder M et al (1998) Structural maintenance of chromosomes protein C-terminal domains bind preferentially to DNA with secondary structure. J Biol Chem 273:24088–24094
Al Hussain TO, Akhtar M (2013) Molecular basis of urinary bladder cancer. Adv Anat Pathol 20:53–60
Amara S, Slama IB, Omri K, et al (2013) Effects of nanoparticle zinc oxide on emotional behavior and trace element homeostasis in rat brain. Toxicol Ind Health. doi: 10.1177/0748233713491802
Batchelor E, Loewer A, Lahav G (2009) The ups and downs of p53: understanding protein dynamics in single cells. Nat Rev Cancer 9:371–377
Ben-Moshe T, Sammy Frenk S, Dror I et al (2013) Effects of metal oxide nanoparticles on soil properties. Chemosphere 90:640–646
Benton MG, Glasser NR, Palecek SP (2007) The utilization of a Saccharomyces cerevisiae HUG1P-GFP promoter-reporter construct for the selective detection of DNA damage. Mutat Res 633:21–34
Benton MG, Glasser NR, Palecek SP (2008) Deletion of MAG1 and MRE11 enhances the sensitivity of the Saccharomyces cerevisiae HUG1P-GFP promoter-reporter construct to genotoxicity. Biosens Bioelectron 24:736–741
Bleda M, Medina I, Alonso R et al (2012) Inferring the regulatory network behind a gene expression experiment. Nucleic Acids Res 40:168–172
Bouraoui S, Mougou S, Brahem A et al (2013) A combination of micronucleus assay and fluorescence in situ hybridization analysis to evaluate the genotoxicity of formaldehyde. Arch Environ Contam Toxicol 64:337–344
Cabrera GL, Rodriguez DMG (1999) Genotoxicity of soil from farmland irrigated with wastewater using three plant biossays. Mutat Res 426:211–214
Chew WS, Poh KW, Siddiqi NJ et al (2012) Short- and long-term changes in blood miRNA levels after nanogold injection in rats–potential biomarkers of nanoparticle exposure. Biomarkers 17:750–757
Dinant C, Houtsmuller AB, Vermeulen W (2008) Chromatin structure and DNA damage repair. Epigenetics Chromatin 1:9
Eastman PS, Ruan W, Doctolero M et al (2006) Qdot nanobarcodes for multiplexed gene expression analysis. Nano Lett 6:1059–1064
Ema M, Tanaka J, Kobayashi N et al (2012) Genotoxicity evaluation of fullerene C60 nanoparticles in a comet assay using lung cells of intratracheally instilled rats. Regul Toxicol Pharmacol 62:419–424
Flower NAL, Brabu B, Revathy M et al (2012) Characterization of synthesized silver nanoparticles and assessment of its genotoxicity potentials using the alkaline comet assay. Mutat Res 742:61–65
Foster SS, De S, Johnson LK, Petrini JH et al (2012) Cell cycle- and DNA repair pathway-specific effects of apoptosis on tumor suppression. Proc Natl Acad Sci U S A 109:9953–9958
Fujita K, Horie M, Kato H et al (2009a) Effects of ultrafine TiO2 particles on gene expression profile in human keratinocytes without illumination: involvement of extracellular matrix and cell adhesion. Toxicol Lett 191:109–117
Fujita K, Morimoto Y, Ogami A et al (2009b) Gene expression profiles in rat lung after inhalation exposure to C60 fullerene particles. Toxicology 258:47–55
Gajjar P, Pettee B, Britt DW et al (2009) Antimicrobial activities of commercial nanoparticles against an environmental soil microbe, Pseudomonas putida KT2440. J Biol Eng 3:1–13
Gardener BBM, Weller DM (2001) Changes in populations of rhizosphere bacteria associated with take-all disease of wheat. Appl Environ Microbiol 67:4414–4425
Ge Y, Schimel JP, Holden PA (2012) Identification of soil bacteria susceptible to TiO2 and ZnO nanoparticles. Appl Environ Microbiol 78:6749–6758
Ghosh M, Bandyopadhyay M, Mukherjee A (2010) Genotoxicity of titanium dioxide (TiO2) nanoparticles at two trophic levels: Plant and human lymphocytes. Chemosphere 81:1253–1262
Giono LE, Manfredi JJ (2006) The p53 tumor suppressor participates in multiple cell cycle checkpoints. J Cell Physiol 209:13–20
Goetze S, Mateos-Langerak J, van Driel R (2007) Three-dimensional genome organization in interphase and its relation to genome function. Semin Cell Dev Biol 18:707–714
Gomes SI, Soares AM, Scott-Fordsmand JJ et al (2013) Mechanisms of response to silver nanoparticles on Enchytraeus albidus (Oligochaeta): survival, reproduction and gene expression profile. J Hazard Mater 254–255:336–344
González-González M, Muñoz-Bellvis L, Mackintosh C et al (2012) Prognostic impact of del(17p) and del(22q) as assessed by interphase FISH in sporadic colorectal carcinomas. PLoS One 7:e42683
Guccini S, Lombardi S, Pisani A et al (2012) Effects of spindle poisons in peripheral human lymphocytes by the in vitro cytokinesis-block micronucleus assay. Mutagenesis 27:749–758
Han Z, Wei W, Dunaway S, Darnowski JW et al (2002) Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin. J Biol Chem 277:17154–17160
Harper JW, Elledge SJ (2007) The DNA damage response: ten years after. Mol Cell 28:739–745
Herzog CR, Bodon N, Pittman B et al (2004) Carcinogen-specific targeting of chromosome 12 for loss of heterozygosity in mouse lung adenocarcinomas: implications for chromosome instability and tumor progression. Oncogene 23:3033–3039
Herzog CR, Desai D, Amin S (2006) Array CGH analysis reveals chromosomal aberrations in mouse lung adenocarcinomas induced by the human lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Biochem Biophys Res Commun 341:856–863
Hoeijmakers JH (2009) DNA damage, aging, and cancer. N Engl J Med 361:1475–1485
Huanga Y, Gao H, Gou M et al (2010) Acute toxicity and genotoxicity studies on poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) nanomaterials. Mutat Res 696:101–106
Hubner MR, Spector DL (2010) Chromatin dynamics. Annu Rev Biophys 39:471–489
Hudler P (2012) Genetic aspects of gastric cancer instability. ScientificWorldJournal 2012:761909
Husain M, Saber AT, Guo C et al (2013) Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation. Toxicol Appl Pharmacol 269:250–262
Jabbur JR, Huang P, Zhang W (2000) DNA damage-induced phosphorylation of p53 at serine 20 correlates with p21 and Mdm-2 induction in vivo. Oncogene 19:6203–6208
Jeon SY, Park JS, Yang HN et al (2012) Co-delivery of SOX9 genes and anti-Cbfa-1 siRNA coated onto PLGA nanoparticles for chondrogenesis of human MSCs. Biomaterials 3:4413–4423
Kadota M, Sato M, Duncan D et al (2009) Identification of novel gene amplifications in breast cancer and coexistence of gene amplification with an activating mutation of PIK3CA. Cancer Res 69:7357–7365
Kumari M, Mukherjee A, Chandrasekaran N (2009) Genotoxicity of silver nanoparticles in Allium cepa. Sci Total Environ 407:5243–5246
Kumari M, Khan SS, Pakrashi S et al (2011) Cytogenetic and genotoxic effects of zinc oxide nanoparticles on root cells of Allium cepa. J Hazard Mater 190:613–621
Leme DM, Marin-Morales MA (2009) Allium cepa test in environmental monitoring: a review on its application. Mutat Res 682:71–81
Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323–331
Liao M, Liu H (2012) Gene expression profiling of nephrotoxicity from copper nanoparticles in rats after repeated oral administration. Environ Toxicol Pharmacol 34:67–80
Lima R, Feitosa L, Pereira AES et al (2010) Evaluation of the genotoxicity of chitosan nanoparticles for use in food packaging films. J Food Sci 75:N89–N96
Lima R, Pereira AES, Porto RM et al (2011) Evaluation of cyto- and genotoxicity of poly(lactide-co-glycolide) nanoparticles. J Polym Environ 19:196–202
Lima R, Feitosa LO, Maruyama CR et al (2012a) Evaluation of the genotoxicity of cellulose nanofibers. Int J Nanomedicine 7:3555–3565
Lima R, Seabra AB, Durán N (2012b) Silver nanoparticles: a brief review of cytotoxicity and genotoxicity of chemically and biogenically synthesized nanoparticles. J Appl Toxicol 32:867–879
Ma TH, Cabrera GL, Owens E (2005) Genotoxic agents detected by plant bioassays. Rev Environ Health 20:1–13
Mateuca R, Lombaert N, Aka PV et al (2006) Chromosomal changes: induction, detection methods and applicability in human biomonitoring. Biochimie 88:1515–1531
Merhia M, Dombua CY, Brient A et al (2012) Study of serum interaction with a cationic nanoparticle: implications for in vitro endocytosis, cytotoxicity and genotoxicity. Int J Pharm 423:37–44
Migliore L, Migheli F, Spisni R, et al (2011) Genetics, cytogenetics, and epigenetics of colorectal cancer. J Biomed Biotechnol ID 792362:1–19
Mitchell RJ, Gu MB (2004) An Escherichia coli biosensor capable of detecting both genotoxic and oxidative damage. Appl Microbiol Biotechnol 64:46–52
Mo Y, Wan R, Zhang Q (2012) Application of reverse transcription-PCR and real-time PCR in nanotoxicity research. Methods Mol Biol 926:99–112
Moore AS, Faisal A, Castro DG et al (2012) Selective FLT3 inhibition of FLT3-ITD + acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns. Leukemia 26:1462–1470
Neri G, Opitz JM (2009) Down syndrome: comments and reflections on the 50th anniversary of Lejeune’s discovery. Am J Med Genet 149A:2647–2654
Nogueira V, Lopes I, Rocha-Santos T et al (2012) Impact of organic and inorganic nanomaterials in the soil microbial community structure. Sci Total Environ 424:344–350
Paino IMM, Marangoni VS, Oliveira RCS et al (2012) Cyto- and genotoxicity of gold nanoparticles in human hepatocellular carcinoma and peripheral blood mononuclear cells. Toxicol Lett 215:119–125
Papis E, Gornati R, Prati M et al (2007) Gene expression in nanotoxicology research: analysis by differential display in BALB3T3 fibroblasts exposed to cobalt particles and ions. Toxicol Lett 170:185–192
Perreault F, Melegari SP, Costa CH et al (2012) Genotoxic effects of copper oxide nanoparticles in Neuro 2A cell cultures. Sci Total Environ 441:117–124
Piazza R, Valletta S, Winkelmann N et al (2012) Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nat Genet 45:18–24
Rao CV, Yamada HY (2013) Genomic instability and colon carcinogenesis: from the perspective of genes. Front Oncol 3:130. doi:10.3389/fonc.2013.00130
Ravikumar S, Pham VD, Lee SH et al (2012) Modification of CusSR bacterial two-component systems by the introduction of an inducible positive feedback loop. J Ind Microbiol Biotechnol 39:861–868
Roylance R, Endesfelder D, Gorman P et al (2011) Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer. Cancer Epidemiol Biomarkers Prev 20:2183–2194
Schwieger F, Tebbe CC (2000) Effect of field inoculation with Sinorhizobium meliloti L33 on the composition of bacterial communities in Rhizospheres of a Target Plant (Medicago sativa) and a non-target plant (Chenopodium album)-linking of 16S rRNA gene-based single-strand conformation polymorphism community profiles to the diversity of cultivated bacteria. Appl Environ Microbiol 66:3556–3565
Shin HJ, Park HH, Lim WK (2005) Freeze-dried recombinant bacteria for on-site detection of phenolic compounds by color change. J Biotechnol 119:36–43
Skinner SO, Sepúlveda LA, Xu H et al (2013) Measuring mRNA copy number in individual Escherichia coli cells using single-molecule fluorescent in situ hybridization. Nat Protoc 8:1100–1113
Soria G, Polo SE, Almouznil (2012) Prime, repair, restore: the active role of chromatin in the DNA damage response. Mol Cell 46(6):722–734
Stirling PC, Bloom MS, Solanki-Patil T et al (2011) The complete spectrum of yeast chromosome instability genes identifies candidate CIN cancer genes and functional roles for ASTRA complex components. PLoS Genet 7:e1002057
Strachan T, Read AP (1999) Human molecular genetics, 2nd edn. Wiley-Liss, New York. http://www.ncbi.nlm.nih.gov/books/NBK7580/
Sun X, Sheng Z, Liu Y (2012) Effects of silver nanoparticles on microbial community structure in activated sludge. Sci Total Environ 443:828–835
Szendi K, Varga C (2008) Lack of genotoxicity of carbon nanotubes in a pilot study. Anticancer Res 28:349–352
Tsaousi A, Jones E, Case CP (2010) The in vitro genotoxicity of orthopaedic ceramic (Al2O3) and metal (CoCr alloy) particles. Mutat Res 697:1–9
Vasconcelos DS, da Silva FP, Quintana LG, et al (2013) Numerical aberrations of chromosome 17 and TP53 in brain metastases derived from breast cancer. Genet Mol Res 12. http://iah.iec.pa.gov.br/iah/fulltext/pc/artigos/2013/genetmol res2013prelo.pdf
Veschure PJ (2006) Chromosome organization and gene control: it is difficult to see the picture when you are inside the frame. J Cell Biochem 99:24–35
Wang J, Yi X, Tang H et al (2012) Direct quantification of microRNA at low picomolar level in sera of glioma patients using a competitive hybridization followed by amplified voltammetric detection. Anal Chem 84:6400–6406
Wilkins G (2013) DNA: Twin strands solved the structure. Nature 496:434. doi:10.1038/496434b
Xiu ZM, Gregory KB, Lowry GV et al (2010) Effect of bare and coated nanoscale zerovalent iron on tceA and vcrA gene expression in Dehalococcoides spp. Environ Sci Technol 44:7647–7651
Yagi K (2007) Applications of whole-cell bacterial sensors in biotechnology and environmental science. Appl Microbiol Biotechnol 73:1251–1258
Yagur-Kroll S, Bilic B, Belkin S (2010) Strategies for enhancing bioluminescent bacterial sensor performance by promoter region manipulation. Bioeng Bugs 1:151–153
Zhou BB, Elledge SJ (2000) The DNA damage response: putting checkpoints in perspective. Nature 408:433–439
Acknowledgements
Supported by FAPESP, CNPq, Brazilian Network on Nanotoxicology (MCTI/CNPq), INOMAT (CNPq), NanoBioss (CMTI/CNPq).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this chapter
Cite this chapter
de Lima, R., Fraceto, L.F. (2014). Genetic Studies on the Effects of Nanomaterials. In: Durán, N., Guterres, S., Alves, O. (eds) Nanotoxicology. Nanomedicine and Nanotoxicology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8993-1_8
Download citation
DOI: https://doi.org/10.1007/978-1-4614-8993-1_8
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-8992-4
Online ISBN: 978-1-4614-8993-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)