Skip to main content

Advertisement

SpringerLink
Log in

Comet assay: an essential tool in toxicological research

  • Review Article
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

The comet assay is a versatile, reliable, cost-efficient, and fast technique for detecting DNA damage and repair in any tissue. It is useable in almost any cell type and applicable to both eukaryotic and prokaryotic organisms. Instead of highlighting one of the numerous specific aspects of the comet assay, the present review aims at giving an overview about the evolution of this widely applicable method from the first description by Ostling and Johanson to the OECD Guideline 489 for the in vivo mammalian comet assay. In addition, methodical aspects and the influence of critical steps of the assay as well as the evaluation of results and improvements of the method are reviewed. Methodical aspects regarding oxidative DNA damage and repair are also addressed. An overview about the most recent works and relevant cutting-edge reviews based on the comet assay with special regard to, e.g., clinical applications, nanoparticles or environmental risk assessment concludes this review. Taken together, the presented overview raises expectations to further decades of successful applications and enhancements of this excellent method.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

According to European Food Safety Authority (2012), OECD (2014)

Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aborgiba M, Kostic J, Kolarevic S, Kracun-Kolarevic M, Elbahi S, Knezevic-Vukcevic J, Lenhardt M, Paunovic M, Gacic Z, Vukovic-Gacic B (2016) Flooding modifies the genotoxic effects of pollution on a worm, a mussel and two fish species from the Sava River. Sci Total Environ 540:358–367

    Article  CAS  PubMed  Google Scholar 

  • Abubakar IB, Lim KH, Kam TS, Loh HS (2016) Synergistic cytotoxic effects of combined delta-tocotrienol and jerantinine B on human brain and colon cancers. J Ethnopharmacol 184:107–118. doi:10.1016/j.jep.2016.03.004

    Article  CAS  PubMed  Google Scholar 

  • Ahnström G, Erixon K (1981) Measurement of strand breaks by alkaline denaturation and hydroxyapatite chromatography. In: Friedberg EC, Hanawalt PC (eds) DNA repair. A laboratory manual of research procedures. Marcel Dekker, New York, pp 403–418

    Google Scholar 

  • Akdag MZ, Dasdag S, Canturk F, Karabulut D, Caner Y, Adalier N (2016) Does prolonged radiofrequency radiation emitted from Wi-Fi devices induce DNA damage in various tissues of rats? J Chem Neuroanat. doi:10.1016/j.jchemneu.2016.01.003

  • Akhtar MF, Ashraf M, Anjum AA, Javeed A, Sharif A, Saleem A, Akhtar B (2016a) Textile industrial effluent induces mutagenicity and oxidative DNA damage and exploits oxidative stress biomarkers in rats. Environ Toxicol Pharmacol 41:180–186

    Article  CAS  PubMed  Google Scholar 

  • Akhtar MF, Ashraf M, Javeed A, Anjum AA, Sharif A, Saleem A, Akhtar B, Khan AM, Altaf I (2016b) Toxicity appraisal of untreated dyeing industry wastewater based on chemical characterization and short term bioassays. Bull Environ Contam Toxicol 96:502–507

    Article  CAS  PubMed  Google Scholar 

  • Alarifi S, Ali D, Al-Bishri W (2016) In vitro apoptotic and DNA damaging potential of nanobarium oxide. Int J Nanomed 12:249–257

    Google Scholar 

  • Albert O, Reintsch WE, Chan P, Robaire B (2016) HT-COMET: a novel automated approach for high throughput assessment of human sperm chromatin quality. Hum Reprod 31(5):938–946. doi:10.1093/humrep/dew030

    Article  PubMed  Google Scholar 

  • Alcaraz-Contreras Y, Mendoza-Lozano RP, Martinez-Alcaraz ER, Martinez-Alfaro M, Gallegos-Corona MA, Ramirez-Morales MA, Vazquez-Guevara MA (2016) Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats. Hum Exp Toxicol 35:398–403

    Article  CAS  PubMed  Google Scholar 

  • Ali H, Dixit S, Ali D, Alkahtane AA, Alarifi S, Ali BA, Alkahtani S (2016) Isolation and evaluation of biological efficacy of quercetol in human hepatic carcinoma cells. Drug Des Devel Ther 10:155–162

    Article  PubMed  PubMed Central  Google Scholar 

  • Alves JS, Silva FR, Silva GF, Salvador M, Kvitko K, Rohr P, Santos CE, Dias JF, Henriques JA, Silva JD (2016) Investigation of potential biomarkers for the early diagnosis of cellular stability after the exposure of agricultural workers to pesticides. An Acad Bras Cienc 88:349–360

    Article  PubMed  Google Scholar 

  • Aquino T, Zenkner FF, Ellwanger JH, Pra D, Rieger A (2016) DNA damage and cytotoxicity in pathology laboratory technicians exposed to organic solvents. An Acad Bras Cienc 88:227–236

    Article  PubMed  Google Scholar 

  • Araldi RP, de Melo TC, Mendes TB, de Sa Junior PL, Nozima BH, Ito ET, de Carvalho RF, de Souza EB, de Cassia SR (2015) Using the comet and micronucleus assays for genotoxicity studies: a review. Biomed Pharmacother 72:74–82

    Article  CAS  PubMed  Google Scholar 

  • Arbo MD, Silva R, Barbosa DJ, da Silva D, Silva SP, Teixeira JP, Bastos ML, Carmo H (2016) In vitro neurotoxicity evaluation of piperazine designer drugs in differentiated human neuroblastoma SH-SY5Y cells. J Appl Toxicol 36:121–130

    Article  CAS  PubMed  Google Scholar 

  • Ataseven N, Yuzbasioglu D, Keskin AC, Unal F (2016) Genotoxicity of monosodium glutamate. Food Chem Toxicol 91:8–18

    Article  CAS  PubMed  Google Scholar 

  • Attia SM, Ahmad SF, Saquib Q, Harisa GI, Al-Khedhairy AA, Bakheet SA (2016) Dexrazoxane mitigates epirubicin-induced genotoxicity in mice bone marrow cells. Mutagenesis 31:137–145

    Article  CAS  PubMed  Google Scholar 

  • Au WW, Giri AK, Ruchirawat M (2010) Challenge assay: a functional biomarker for exposure-induced DNA repair deficiency and for risk of cancer. Int J Hyg Environ Health 213:32–39

    Article  CAS  PubMed  Google Scholar 

  • Augustyniak M, Gladysz M, Dziewiecka M (2016) The Comet assay in insects—status, prospects and benefits for science. Mutat Res Rev Mutat Res 767:67–76

    Article  CAS  PubMed  Google Scholar 

  • Azqueta A, Collins AR (2013) The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch Toxicol 87:949–968

    Article  CAS  PubMed  Google Scholar 

  • Azqueta A, Gutzkow KB, Brunborg G, Collins AR (2011a) Towards a more reliable comet assay: optimising agarose concentration, unwinding time and electrophoresis conditions. Mutat Res 724:41–45

    Article  CAS  PubMed  Google Scholar 

  • Azqueta A, Meier S, Priestley C, Gutzkow KB, Brunborg G, Sallette J, Soussaline F, Collins A (2011b) The influence of scoring method on variability in results obtained with the comet assay. Mutagenesis 26:393–399

    Article  CAS  PubMed  Google Scholar 

  • Azqueta A, Gutzkow KB, Priestley CC, Meier S, Walker JS, Brunborg G, Collins AR (2013) A comparative performance test of standard, medium- and high-throughput comet assays. Toxicol In Vitro 27:768–773

    Article  CAS  PubMed  Google Scholar 

  • Azqueta A, Slyskova J, Langie SA, O’Neill GI, Collins A (2014) Comet assay to measure DNA repair: approach and applications. Front Genet 5:288

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bakuradze T, Lang R, Hofmann T, Schipp D, Galan J, Eisenbrand G, Richling E (2016) Coffee consumption rapidly reduces background DNA strand breaks in healthy humans: results of a short-term repeated uptake intervention study. Mol Nutr Food Res 60:682–686

    Article  CAS  PubMed  Google Scholar 

  • Baldissera MD, Sagrillo MR, de Sa MF, Grando TH, Souza CF, de Brum GF, da Luz SC, Oliveira SS, De Mello AL, Nascimento K, Tatsch E, Moresco RN, da Silva AS, Monteiro SG (2016) Relationship between DNA damage in liver, heart, spleen and total blood cells and disease pathogenesis of infected rats by Trypanosoma evansi. Exp Parasitol 161:12–19

    Article  CAS  PubMed  Google Scholar 

  • Banerjee P, Dey TK, Sarkar S, Swarnakar S, Mukhopadhyay A, Ghosh S (2016) Treatment of cosmetic effluent in different configurations of ceramic UF membrane based bioreactor: toxicity evaluation of the untreated and treated wastewater using catfish (Heteropneustes fossilis). Chemosphere 146:133–144

    Article  CAS  PubMed  Google Scholar 

  • Baron E, Dissanayake A, Vila-Cano J, Crowther C, Readman JW, Jha AN, Eljarrat E, Barcelo D (2016) Evaluation of the genotoxic and physiological effects of decabromodiphenyl ether (BDE-209) and Dechlorane Plus (DP) flame retardants in marine mussels (Mytilus galloprovincialis). Environ Sci Technol 50:2700–2708

    Article  CAS  PubMed  Google Scholar 

  • Basri DF, Alamin ZA, Chan KM (2016) Assessment of cytotoxicity and genotoxicity of stem bark extracts from Canarium odontophyllum Miq. (dabai) against HCT 116 human colorectal cancer cell line. BMC Complement Altern Med 16:36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bausinger J, Speit G (2015) DNA repair capacity of cultured human lymphocytes exposed to mutagens measured by the comet assay and array expression analysis. Mutagenesis 30:811–820

    Article  CAS  PubMed  Google Scholar 

  • Bausinger J, Schutz P, Piberger AL, Speit G (2016) Further characterization of benzo[a]pyrene diol-epoxide (BPDE)-induced comet assay effects. Mutagenesis 31:161–169

    Article  CAS  PubMed  Google Scholar 

  • Bedekar PA, Saratale RG, Saratale GD, Govindwar SP (2014) Oxidative stress response in dye degrading bacterium Lysinibacillus sp. RGS exposed to Reactive Orange 16, degradation of RO16 and evaluation of toxicity. Environ Sci Pollut Res Int 21:11075–11085

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharya P, Swarnakar S, Mukhopadhyay A, Ghosh S (2016) Exposure of composite tannery effluent on snail, Pila globosa: a comparative assessment of toxic impacts of the untreated and membrane treated effluents. Ecotoxicol Environ Saf 126:45–55

    Article  CAS  PubMed  Google Scholar 

  • Bilbao C, Ferreiro JA, Comendador MA, Sierra LM (2002) Influence of mus201 and mus308 mutations of Drosophila melanogaster on the genotoxicity of model chemicals in somatic cells in vivo measured with the comet assay. Mutat Res 503:11–19

    Article  CAS  PubMed  Google Scholar 

  • Boyacioglu M, Kum C, Sekkin S, Yalinkilinc HS, Avci H, Epikmen ET, Karademir U (2016) The effects of lycopene on DNA damage and oxidative stress on indomethacin-induced gastric ulcer in rats. Clin Nutr 35:428–435

    Article  CAS  PubMed  Google Scholar 

  • Brunborg G, Jackson P, Shaposhnikov S, Dahl H, Azqueta A, Collins AR, Gutzkow KB (2014) High throughput sample processing and automated scoring. Front Genet 5:373

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brusehafer K, Manshian BB, Doherty AT, Zair ZM, Johnson GE, Doak SH, Jenkins GJ (2016) The clastogenicity of 4NQO is cell-type dependent and linked to cytotoxicity, length of exposure and p53 proficiency. Mutagenesis 31:171–180

    Article  PubMed  CAS  Google Scholar 

  • Caballero-Gallardo K, Olivero-Verbel J (2016) Mice housed on coal dust-contaminated sand: a model to evaluate the impacts of coal mining on health. Toxicol Appl Pharmacol 294:11–20

    Article  CAS  PubMed  Google Scholar 

  • Carbajal-Lopez Y, Gomez-Arroyo S, Villalobos-Pietrini R, Calderon-Segura ME, Martinez-Arroyo A (2016) Biomonitoring of agricultural workers exposed to pesticide mixtures in Guerrero state, Mexico, with comet assay and micronucleus test. Environ Sci Pollut Res Int 23:2513–2520

    Article  CAS  PubMed  Google Scholar 

  • Carter RJ, Parsons JL (2016) Base excision repair: a pathway regulated by post-translational modifications. Mol Cell Biol 36(10):1426–1437. doi:10.1128/MCB.00030-16

    Article  CAS  PubMed  Google Scholar 

  • Carvalho IC, Dutra TP, De Andrade DP, Balducci I, Pacheco-Soares C, Rocha RF (2016) High doses of alcohol during pregnancy cause DNA damages in osteoblasts of newborns rats. Birth Defects Res A Clin Mol Teratol 106:122–132

    Article  CAS  PubMed  Google Scholar 

  • Carvalho-Silva R, Pereira AC, Dos Santos Alves RP, Guecheva TN, Henriques JA, Brendel M, Pungartnik C, Rios-Santos F (2016) DNA protection against oxidative damage using the hydroalcoholic extract of Garcinia mangostana and alpha-mangostin. Evid Based Complement Alternat Med 2016:3430405

    Article  PubMed  PubMed Central  Google Scholar 

  • Castilla JA, Zamora S, Gonzalvo MC, Luna Del Castillo JD, Roldan-Nofuentes JA, Clavero A, Bjorndahl L, Martinez L (2010) Sperm chromatin structure assay and classical semen parameters: systematic review. Reprod Biomed Online 20:114–124

    Article  CAS  PubMed  Google Scholar 

  • Cetinkaya N, Ercin D, Ozvatan S, Erel Y (2016) Quantification of applied dose in irradiated citrus fruits by DNA Comet Assay together with image analysis. Food Chem 192:370–373

    Article  CAS  PubMed  Google Scholar 

  • Chandramohan B, Murugan K, Panneerselvam C, Madhiyazhagan P, Chandirasekar R, Dinesh D, Kumar PM, Kovendan K, Suresh U, Subramaniam J, Rajaganesh R, Aziz AT, Syuhei B, Alsalhi MS, Devanesan S, Nicoletti M, Wei H, Benelli G (2016) Characterization and mosquitocidal potential of neem cake-synthesized silver nanoparticles: genotoxicity and impact on predation efficiency of mosquito natural enemies. Parasitol Res 115:1015–1025

    Article  PubMed  Google Scholar 

  • Chang L, Huang J, Wang K, Li J, Yan R, Zhu L, Ye J, Wu X, Zhuang S, Li D, Zhang G (2016a) Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy. BMC Cancer 16:190

    Article  PubMed  PubMed Central  Google Scholar 

  • Chang YT, Huang CY, Li KT, Li RN, Liaw CC, Wu SH, Liu JR, Sheu JH, Chang HW (2016b) Sinuleptolide inhibits proliferation of oral cancer Ca9-22 cells involving apoptosis, oxidative stress, and DNA damage. Arch Oral Biol 66:147–154

    Article  CAS  PubMed  Google Scholar 

  • Chapman PM (2007) Determining when contamination is pollution—weight of evidence determinations for sediments and effluents. Environ Int 33:492–501

    Article  CAS  PubMed  Google Scholar 

  • Chen LM, Peng F, Li GD, Jie XM, Cai KR, Cai C, Zhong Y, Zeng H, Li W, Zhang Z, Chen JC (2016) The studies on the cytotoxicity in vitro, cellular uptake, cell cycle arrest and apoptosis-inducing properties of ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)]. J Inorg Biochem 156:64–74

    Article  CAS  PubMed  Google Scholar 

  • Cigerci IH, Ali MM, Kaygisiz SY, Liman R (2016) Genotoxicity assessment of cobalt chloride in Eisenia hortensis earthworms coelomocytes by comet assay and micronucleus test. Chemosphere 144:754–757

    Article  CAS  PubMed  Google Scholar 

  • Claudio SR, Gollucke AP, Yamamura H, Morais DR, Bataglion GA, Eberlin MN, Peres RC, Oshima CT, Ribeiro DA (2016) Purple carrot extract protects against cadmium intoxication in multiple organs of rats: genotoxicity, oxidative stress and tissue morphology analyses. J Trace Elem Med Biol 33:37–47

    Article  CAS  PubMed  Google Scholar 

  • Collins AR (2009) Investigating oxidative DNA damage and its repair using the comet assay. Mutat Res 681:24–32

    Article  CAS  PubMed  Google Scholar 

  • Collins AR (2014) Measuring oxidative damage to DNA and its repair with the comet assay. Biochim Biophys Acta 1840:794–800

    Article  CAS  PubMed  Google Scholar 

  • Collins AR, Azqueta A (2012) DNA repair as a biomarker in human biomonitoring studies; further applications of the comet assay. Mutat Res 736:122–129

    Article  CAS  PubMed  Google Scholar 

  • Collins AR, Horvathova E (2001) Oxidative DNA damage, antioxidants and DNA repair: applications of the comet assay. Biochem Soc Trans 29:337–341

    Article  CAS  PubMed  Google Scholar 

  • Collins AR, Duthie SJ, Dobson VL (1993) Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA. Carcinogenesis 14:1733–1735

    Article  CAS  PubMed  Google Scholar 

  • Collins A, Dusinska M, Franklin M, Somorovska M, Petrovska H, Duthie S, Fillion L, Panayiotidis M, Raslova K, Vaughan N (1997a) Comet assay in human biomonitoring studies: reliability, validation, and applications. Environ Mol Mutagen 30:139–146

    Article  CAS  PubMed  Google Scholar 

  • Collins AR, Dobson VL, Dusinska M, Kennedy G, Stetina R (1997b) The comet assay: what can it really tell us? Mutat Res 375:183–193

    Article  CAS  PubMed  Google Scholar 

  • Collins AR, Olmedilla B, Southon S, Granado F, Duthie SJ (1998) Serum carotenoids and oxidative DNA damage in human lymphocytes. Carcinogenesis 19:2159–2162

    Article  CAS  PubMed  Google Scholar 

  • Collins AR, Oscoz AA, Brunborg G, Gaivao I, Giovannelli L, Kruszewski M, Smith CC, Stetina R (2008) The comet assay: topical issues. Mutagenesis 23:143–151

    Article  CAS  PubMed  Google Scholar 

  • Collins A, Koppen G, Valdiglesias V, Dusinska M, Kruszewski M, Moller P, Rojas E, Dhawan A, Benzie I, Coskun E, Moretti M, Speit G, Bonassi S (2014) The comet assay as a tool for human biomonitoring studies: the ComNet project. Mutat Res Rev Mutat Res 759:27–39

    Article  CAS  PubMed  Google Scholar 

  • Cordelli E, Keller J, Eleuteri P, Villani P, Ma-Hock L, Schulz M, Landsiedel R, Pacchierotti F (2016) No genotoxicity in rat blood cells upon 3- or 6-month inhalation exposure to CeO2 or BaSO4 nanomaterials. Mutagenesis [Epub ahead of print]

  • Coronas MV, Vaz Rocha JA, Favero Salvadori DM, Vargas VF (2016) Evaluation of area contaminated by wood treatment activities: genetic markers in the environment and in the child population. Chemosphere 144:1207–1215

    Article  CAS  PubMed  Google Scholar 

  • Corredor Z, Rodriguez-Ribera L, Coll E, Montanes R, Diaz JM, Ballarin J, Marcos R, Pastor S (2016) Unfermented grape juice reduce genomic damage on patients undergoing hemodialysis. Food Chem Toxicol 92:1–7

    Article  CAS  PubMed  Google Scholar 

  • Cortes-Gutierrez EI, Lopez-Fernandez C, Fernandez JL, Vila-Rodriguez MI, Johnston SD, Gosalvez J (2014) Interpreting sperm DNA damage in a diverse range of mammalian sperm by means of the two-tailed comet assay. Front Genet 5:404

    PubMed  PubMed Central  Google Scholar 

  • Costa JG, Saraiva N, Guerreiro PS, Louro H, Silva MJ, Miranda JP, Castro M, Batinic-Haberle I, Fernandes AS, Oliveira NG (2016) Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: an integrative approach of complementary endpoints. Food Chem Toxicol 87:65–76

    Article  CAS  PubMed  Google Scholar 

  • Cui H, Wu S, Sun Y, Wang T, Li Z, Chen M, Wang C (2016) Polysaccharide from Pleurotus nebrodensis induces apoptosis via a mitochondrial pathway in HepG2 cells. Food Funct 7:455–463

    Article  CAS  PubMed  Google Scholar 

  • Curnow A, Owen SJ (2016) An evaluation of root phytochemicals derived from Althea officinalis (Marshmallow) and Astragalus membranaceus as potential natural components of UV protecting dermatological formulations. Oxid Med Cell Longev 2016:7053897

    Article  PubMed  PubMed Central  Google Scholar 

  • Danevcic T, Boric VM, Tabor M, Zorec M, Stopar D (2016) Prodigiosin induces autolysins in actively grown Bacillus subtilis cells. Front Microbiol 7:27

    Article  PubMed  PubMed Central  Google Scholar 

  • Darne C, Coulais C, Terzetti F, Fontana C, Binet S, Gate L, Guichard Y (2016) In vitro comet and micronucleus assays do not predict morphological transforming effects of silica particles in Syrian Hamster Embryo cells. Mutat Res Genet Toxicol Environ Mutagen 796:23–33

    Article  CAS  PubMed  Google Scholar 

  • de Lapuente J, Lourenco J, Mendo SA, Borras M, Martins MG, Costa PM, Pacheco M (2015) The Comet Assay and its applications in the field of ecotoxicology: a mature tool that continues to expand its perspectives. Front Genet 6:180

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • de Oliveira LF, Santos C, Dos Reis Martinez CB (2016) Biomarkers in the freshwater bivalve Corbicula fluminea confined downstream a domestic landfill leachate discharge. Environ Sci Pollut Res Int. doi:10.1007/s11356-016-6567-7

    Google Scholar 

  • DeMarini DM (2013) Genotoxicity biomarkers associated with exposure to traffic and near-road atmospheres: a review. Mutagenesis 28:485–505

    Article  CAS  PubMed  Google Scholar 

  • Dhawan A, Bajpayee M, Parmar D (2009) Comet assay: a reliable tool for the assessment of DNA damage in different models. Cell Biol Toxicol 25:5–32

    Article  CAS  PubMed  Google Scholar 

  • Dissanayake A, Scarlett AG, Jha AN (2016) Diamondoid naphthenic acids cause in vivo genetic damage in gills and haemocytes of marine mussels. Environ Sci Pollut Res Int 23:7060–7066

    Article  CAS  PubMed  Google Scholar 

  • Dobrovolsky VN, Pacheco-Martinez MM, McDaniel LP, Pearce MG, Ding W (2016) In vivo genotoxicity assessment of acrylamide and glycidyl methacrylate. Food Chem Toxicol 87:120–127

    Article  CAS  PubMed  Google Scholar 

  • Du J, Wang S, You H, Jiang R, Zhuang C, Zhang X (2016) Developmental toxicity and DNA damage to zebrafish induced by perfluorooctane sulfonate in the presence of ZnO nanoparticles. Environ Toxicol 31:360–371

    Article  CAS  PubMed  Google Scholar 

  • Duan H, Jia X, Zhai Q, Ma L, Wang S, Huang C, Wang H, Niu Y, Li X, Dai Y, Yu S, Gao W, Chen W, Zheng Y (2016) Long-term exposure to diesel engine exhaust induces primary DNA damage: a population-based study. Occup Environ Med 73:83–90

    Article  PubMed  Google Scholar 

  • Dusinska M, Collins AR (2008) The comet assay in human biomonitoring: gene-environment interactions. Mutagenesis 23:191–205

    Article  CAS  PubMed  Google Scholar 

  • Duthie SJ, Ma A, Ross MA, Collins AR (1996) Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes. Cancer Res 56:1291–1295

    CAS  PubMed  Google Scholar 

  • EFSA Scientific Committee (2011) Scientific opinion on genotoxicity testing strategies applicable to food and feed safety assessment. EFSA J 9:2379–2447

    Article  CAS  Google Scholar 

  • Ersson C, Moller L (2011) The effects on DNA migration of altering parameters in the comet assay protocol such as agarose density, electrophoresis conditions and durations of the enzyme or the alkaline treatments. Mutagenesis 26:689–695

    Article  CAS  PubMed  Google Scholar 

  • Ersson C, Thorman R, Rodhe Y, Moller L, Hylander B (2011) DNA damage in salivary gland tissue in patients with chronic kidney disease, measured by the comet assay. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112:209–215

    Article  PubMed  Google Scholar 

  • European Food Safety Authority (2012) Minimum criteria for the acceptance of in vivo alkaline Comet Assay reports. EFSA J 10:2977–2988

    Article  CAS  Google Scholar 

  • Evison BJ, Actis ML, Fujii N (2016) A clickable psoralen to directly quantify DNA interstrand crosslinking and repair. Bioorg Med Chem 24:1071–1078

    Article  CAS  PubMed  Google Scholar 

  • Ezzi L, Salah IB, Haouas Z, Sakly A, Grissa I, Chakroun S, Kerkeni E, Hassine M, Mehdi M, Ben CH (2016a) Histopathological and genotoxic effects of chlorpyrifos in rats. Environ Sci Pollut Res Int 23(5):4859–4867. doi:10.1007/s11356-015-5722-x

    Article  CAS  PubMed  Google Scholar 

  • Ezzi L, Haouas Z, Salah IB, Sakly A, Grissa I, Chakroun S, Kerkeni E, Hassine M, Mehdi M, Cheikh HB (2016b) Toxicopathic changes and genotoxic effects in liver of rat following exposure to diazinon. Environ Sci Pollut Res Int 23(5):4859–4867. doi:10.1007/s11356-015-5722-x

    Article  CAS  PubMed  Google Scholar 

  • Faisal M, Saquib Q, Alatar AA, Al-Khedhairy AA, Ahmed M, Ansari SM, Alwathnani HA, Dwivedi S, Musarrat J, Praveen S (2016) Cobalt oxide nanoparticles aggravate DNA damage and cell death in eggplant via mitochondrial swelling and NO signaling pathway. Biol Res 49:20

    Article  PubMed  PubMed Central  Google Scholar 

  • Farah MA, Ali MA, Chen SM, Li Y, Al-Hemaid FM, Bou-Tarboush FM, Al-Anazi KM, Lee J (2016) Silver nanoparticles synthesized from Adenium obesum leaf extract induced DNA damage, apoptosis and autophagy via generation of reactive oxygen species. Colloids Surf B Biointerfaces 141:158–169

    Article  PubMed  CAS  Google Scholar 

  • Farhan M, Khan HY, Oves M, Al-Harrasi A, Rehmani N, Arif H, Hadi SM, Ahmad A (2016) Cancer therapy by catechins involves redox cycling of copper ions and generation of reactive oxygenspecies. Toxins (Basel) 8(2):37. doi:10.3390/toxins8020037

  • Fernandez-Encinas A, Garcia-Peiro A, Ribas-Maynou J, Abad C, Amengual MJ, Navarro J, Benet J (2016) Characterization of nuclease activity in human seminal plasma and its relationship to semen parameters, sperm DNA fragmentation and male infertility. J Urol 195:213–219

    Article  CAS  PubMed  Google Scholar 

  • Frenzilli G, Nigro M, Lyons BP (2009) The Comet assay for the evaluation of genotoxic impact in aquatic environments. Mutat Res 681:80–92

    Article  CAS  PubMed  Google Scholar 

  • Gaivao I, Sierra LM (2014) Drosophila comet assay: insights, uses, and future perspectives. Front Genet 5:304

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gasulla J, Picco SJ, Carriquiriborde P, Dulout FN, Ronco AE, de Luca JC (2016) Genotoxic effects induced by Cd, Cr, Cu in the gill and liver of odontesthes bonariensis (Piscies, Atherinopsidae). Bull Environ Contam Toxicol 96(5):591–595. doi:10.1007/s00128-016-1774-y

    Article  CAS  PubMed  Google Scholar 

  • Gelaleti RB, Damasceno DC, Santos DP, Calderon IM, Rudge MV (2016) Increased DNA damage is related to maternal blood glucose levels in the offspring of women with diabetes and mild gestational hyperglycemia. Reprod Sci 23:318–323

    Article  CAS  PubMed  Google Scholar 

  • Girardello F, Leite CC, Vianna VI, da Silva MM, Luiz Mendes JA, Roesch-Ely M, Neves FA, Salvador M, Ntonio Pegas HJ (2016) Titanium dioxide nanoparticles induce genotoxicity but not mutagenicity in golden mussel Limnoperna fortunei. Aquat Toxicol 170:223–228

    Article  CAS  PubMed  Google Scholar 

  • Glei M, Pool-Zobel BL (2006) The main catechin of green tea, (-)-epigallocatechin-3-gallate (EGCG), reduces bleomycin-induced DNA damage in human leucocytes. Toxicol In Vitro 20:295–300

    Article  CAS  PubMed  Google Scholar 

  • Glei M, Schlörmann W (2014) Analysis of DNA damage and repair by comet fluorescence in situ hybridization (Comet-FISH). Methods Mol Biol 1094:39–48

    Article  CAS  PubMed  Google Scholar 

  • Glei M, Latunde-Dada GO, Klinder A, Becker TW, Hermann U, Voigt K, Pool-Zobel BL (2002a) Iron-overload induces oxidative DNA damage in the human colon carcinoma cell line HT29 clone 19A. Mutat Res 519:151–161

    Article  CAS  PubMed  Google Scholar 

  • Glei M, Liegibel UM, Ebert MN, Bohm V, Pool-Zobel BL (2002b) beta-Carotene reduces bleomycin-induced genetic damage in human lymphocytes. Toxicol Appl Pharmacol 179:65–73

    Article  CAS  PubMed  Google Scholar 

  • Glei M, Matuschek M, Steiner C, Bohm V, Persin C, Pool-Zobel BL (2003) Initial in vitro toxicity testing of functional foods rich in catechins and anthocyanins in human cells. Toxicol In Vitro 17:723–729

    Article  CAS  PubMed  Google Scholar 

  • Glei M, Habermann N, Osswald K, Seidel C, Persin C, Jahreis G, Pool-Zobel BL (2005) Assessment of DNA damage and its modulation by dietary and genetic factors in smokers using the Comet assay: a biomarker model. Biomarkers 10:203–217

    Article  CAS  PubMed  Google Scholar 

  • Glei M, Kirmse A, Habermann N, Persin C, Pool-Zobel BL (2006a) Bread enriched with green coffee extract has chemoprotective and antigenotoxic activities in human cells. Nutr Cancer 56:182–192

    Article  CAS  PubMed  Google Scholar 

  • Glei M, Klenow S, Sauer J, Wegewitz U, Richter K, Pool-Zobel BL (2006b) Hemoglobin and hemin induce DNA damage in human colon tumor cells HT29 clone 19A and in primary human colonocytes. Mutat Res 594:162–171

    Article  CAS  PubMed  Google Scholar 

  • Glei M, Schaeferhenrich A, Claussen U, Kuechler A, Liehr T, Weise A, Marian B, Sendt W, Pool-Zobel BL (2007) Comet fluorescence in situ hybridization analysis for oxidative stress-induced DNA damage in colon cancer relevant genes. Toxicol Sci 96:279–284

    Article  CAS  PubMed  Google Scholar 

  • Glei M, Hovhannisyan G, Pool-Zobel BL (2009) Use of Comet-FISH in the study of DNA damage and repair: review. Mutat Res 681:33–43

    Article  CAS  PubMed  Google Scholar 

  • Golbamaki N, Rasulev B, Cassano A, Marchese Robinson RL, Benfenati E, Leszczynski J, Cronin MT (2015) Genotoxicity of metal oxide nanomaterials: review of recent data and discussion of possible mechanisms. Nanoscale 7:2154–2198

    Article  CAS  PubMed  Google Scholar 

  • Gorniak JP, Cameron KM, Waldron KJ, von Zglinicki T, Mathers JC, Langie SA (2013) Tissue differences in BER-related incision activity and non-specific nuclease activity as measured by the comet assay. Mutagenesis 28:673–681

    Article  CAS  PubMed  Google Scholar 

  • Goyal S, Amar SK, Dwivedi A, Mujtaba SF, Kushwaha HN, Chopra D, Pal MK, Singh D, Chaturvedi RK, Ray RS (2016) Photosensitized 2-amino-3-hydroxypyridine-induced mitochondrial apoptosis via Smac/DIABLO in human skin cells. Toxicol Appl Pharmacol 297:12–21

    Article  CAS  PubMed  Google Scholar 

  • Gu L, Gao W, Yang HM, Wang BB, Wang XN, Xu J, Zhang H (2016) Control of Trx1 redox state modulates protection against methyl methanesulfonate-induced DNA damage via stabilization of p21. J Biochem 159:101–110

    Article  CAS  PubMed  Google Scholar 

  • Guerard M, Marchand C, Plappert-Helbig U (2014) Influence of experimental conditions on data variability in the liver comet assay. Environ Mol Mutagen 55:114–121

    Article  CAS  PubMed  Google Scholar 

  • Gugliandolo A, Gangemi C, Calabro C, Vecchio M, Di MD, Renis M, Ientile R, Curro M, Caccamo D (2016) Assessment of glutathione peroxidase-1 polymorphisms, oxidative stress and DNA damage in sensitivity-related illnesses. Life Sci 145:27–33

    Article  CAS  PubMed  Google Scholar 

  • Gulati S, Yadav A, Kumar N, Kanupriya Aggarwal NK, Kumar R, Gupta R (2016) Effect of GSTM1 and GSTT1 polymorphisms on genetic damage in humans populations exposed to radiation from mobile towers. Arch Environ Contam Toxicol 70:615–625

    Article  CAS  PubMed  Google Scholar 

  • Gunasekarana V, Raj GV, Chand P (2015) A comprehensive review on clinical applications of comet assay. J Clin Diagn Res 9:GE01–GE05

    PubMed  PubMed Central  Google Scholar 

  • Gutzkow KB, Langleite TM, Meier S, Graupner A, Collins AR, Brunborg G (2013) High-throughput comet assay using 96 minigels. Mutagenesis 28:333–340

    Article  CAS  PubMed  Google Scholar 

  • Hagmar L, Bonassi S, Stromberg U, Brogger A, Knudsen LE, Norppa H, Reuterwall C (1998) Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res 58:4117–4121

    CAS  PubMed  Google Scholar 

  • Haq I, Kumar S, Kumari V, Singh SK, Raj A (2016) Evaluation of bioremediation potentiality of ligninolytic Serratia liquefaciens for detoxification of pulp and paper mill effluent. J Hazard Mater 305:190–199

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto M, Kawai K, Kawakami H, Imazato S (2016) Matrix metalloproteases inhibition and biocompatibility of gold and platinum nanoparticles. J Biomed Mater Res A 104:209–217

    Article  PubMed  CAS  Google Scholar 

  • Hoda M, Pajaniradje S, Shakya G, Mohankumar K, Rajagopalan R (2016) Anti-proliferative and apoptosis-triggering potential of disulfiram and disulfiram-loaded polysorbate 80-stabilized PLGA nanoparticles on hepatocellular carcinoma Hep3B cell line. Nanomedicine. doi:10.1016/j.nano.2016.02.013

    PubMed  Google Scholar 

  • Hoeijmakers JH (2001) Genome maintenance mechanisms for preventing cancer. Nature 411:366–374

    Article  CAS  PubMed  Google Scholar 

  • Hoeijmakers JH (2009) DNA damage, aging, and cancer. N Engl J Med 361:1475–1485

    Article  CAS  PubMed  Google Scholar 

  • Hofer M, Falk M, Komurkova D, Falkova I, Bacikova A, Klejdus B, Pagacova E, Stefancikova L, Weiterova L, Angelis KJ, Kozubek S, Dusek L, Galbavy S (2016) Two new faces of amifostine: protector from DNA damage in normal cells and inhibitor of DNA repair in cancer cells. J Med Chem 59(7):3003–3017. doi:10.1021/acs.jmedchem.5b01628

    Article  CAS  PubMed  Google Scholar 

  • Horta RN, Kahl VF, Sarmento MS, Nunes MF, Porto CR, Andrade VM, Ferraz AB, Silva JD (2016) Protective effects of acerola juice on genotoxicity induced by iron in vivo. Genet Mol Biol 39:122–128

    Article  PubMed  PubMed Central  Google Scholar 

  • Horvathova E, Dusinska M, Shaposhnikov S, Collins AR (2004) DNA damage and repair measured in different genomic regions using the comet assay with fluorescent in situ hybridization. Mutagenesis 19:269–276

    Article  CAS  PubMed  Google Scholar 

  • Horvathova E, Srancikova A, Regendova-Sedlackova E, Melusova M, Melus V, Netriova J, Krajcovicova Z, Slamenova D, Pastorek M, Kozics K (2016) Enriching the drinking water of rats with extracts of Salvia officinalis and Thymus vulgaris increases their resistance to oxidative stress. Mutagenesis 31:51–59

    CAS  PubMed  Google Scholar 

  • Huan Z, Luo J, Xu Z, Xie D (2016) Acute toxicity and genotoxicity of carbendazim, main impurities and metabolite to earthworms (Eisenia foetida). Bull Environ Contam Toxicol 96:62–69

    Article  CAS  PubMed  Google Scholar 

  • Huang JL, Lu HH, Lu YN, Hung PS, Lin YJ, Lin CC, Yang CC, Wong TY, Lu SY, Lin CS (2016) Enhancement of the genotoxicity of benzo[a]pyrene by arecoline through suppression of DNA repair in HEp-2 cells. Toxicol In Vitro 33:80–87

    Article  CAS  PubMed  Google Scholar 

  • Hylland K, Skei BB, Brunborg G, Lang T, Gubbins MJ, le GJ, Burgeot T (2016) DNA damage in dab (Limanda limanda) and haddock (Melanogrammus aeglefinus) from European seas. Mar Environ Res. doi:10.1016/j.marenvres.2016.01.001

    Google Scholar 

  • Javed M, Ahmad I, Usmani N, Ahmad M (2016a) Bioaccumulation, oxidative stress and genotoxicity in fish (Channa punctatus) exposed to a thermal power plant effluent. Ecotoxicol Environ Saf 127:163–169

    Article  CAS  PubMed  Google Scholar 

  • Javed M, Ahmad I, Usmani N, Ahmad M (2016b) Studies on biomarkers of oxidative stress and associated genotoxicity and histopathology in Channa punctatus from heavy metal polluted canal. Chemosphere 151:210–219

    Article  CAS  PubMed  Google Scholar 

  • Jung SJ, Choi YJ, Kim NN, Choi JY, Kim BS, Choi CY (2016) Effects of melatonin injection or green-wavelength LED light on the antioxidant system in goldfish (Carassius auratus) during thermal stress. Fish Shellfish Immunol 52:157–166

    Article  CAS  PubMed  Google Scholar 

  • Kadam A, Dhabbe R, Gophane A, Sathe T, Garadkar K (2016) Template free synthesis of ZnO/Ag2O nanocomposites as a highly efficient visible active photocatalyst for detoxification of methyl orange. J Photochem Photobiol B 154:24–33

    Article  CAS  PubMed  Google Scholar 

  • Kalaiselvan I, Senthamarai M, Kasi PD (2016) 2,3,7,8-TCDD-mediated toxicity in peripheral blood mononuclear cells is alleviated by the antioxidants present in Gelidiella acerosa: an in vitro study. Environ Sci Pollut Res Int 23:5111–5121

    Article  CAS  PubMed  Google Scholar 

  • Kang SH, Kwon JY, Lee JK, Seo YR (2013) Recent advances in in vivo genotoxicity testing: prediction of carcinogenic potential using comet and micronucleus assay in animal models. J Cancer Prev 18:277–288

    Article  PubMed  PubMed Central  Google Scholar 

  • Karlsson HL, Di BS, Collins AR, Dusinska M (2015) Can the comet assay be used reliably to detect nanoparticle-induced genotoxicity? Environ Mol Mutagen 56:82–96

    Article  CAS  PubMed  Google Scholar 

  • Katz IS, Albuquerque LL, Suppa AP, da Silva GB, Jensen JR, Borrego A, Massa S, Starobinas N, Cabrera WH, De FM, Borelli P, Ibanez OM, Ribeiro OG (2016) 7,12-Dimethylbenz(a)anthracene-induced genotoxicity on bone marrow cells from mice phenotypically selected for low acute inflammatory response. DNA Repair 37:43–52

    Article  CAS  PubMed  Google Scholar 

  • Kelvey-Martin VJ, Green MH, Schmezer P, Pool-Zobel BL, De Meo MP, Collins A (1993) The single cell gel electrophoresis assay (comet assay): a European review. Mutat Res 288:47–63

    Article  Google Scholar 

  • Khoei S, Shoja M, Mostaar A, Faeghi F (2016) Effects of resveratrol and methoxyamine on the radiosensitivity of iododeoxyuridine in U87MG glioblastoma cell line. Exp Biol Med 241(11):1229–1236. doi:10.1177/1535370215622583

    Article  Google Scholar 

  • Kim KC, Piao MJ, Madduma H Sr, Han X, Kang KA, Jo JO, Mok YS, Shin JH, Park Y, Yoo SJ, Hyun JW (2016) Non-thermal dielectric-barrier discharge plasma damages human keratinocytes by inducing oxidative stress. Int J Mol Med 37:29–38

    PubMed  Google Scholar 

  • King YA, Chiu YJ, Chen HP, Kuo DH, Lu CC, Yang JS (2016) Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol 31:314–328

    Article  CAS  PubMed  Google Scholar 

  • Kobets T, Duan JD, Brunnemann KD, Etter S, Smith B, Williams GM (2016) Structure-activity relationships for DNA damage by alkenylbenzenes in Turkey egg fetal liver. Toxicol Sci 150:301–311

    Article  CAS  PubMed  Google Scholar 

  • Kohn KW, Grimek-Ewig RA (1973) Alkaline elution analysis, a new approach to the study of DNA single-strand interruptions in cells. Cancer Res 33:1849–1853

    CAS  PubMed  Google Scholar 

  • Kolarevic S, Kracun-Kolarevic M, Kostic J, Slobodnik J, Liska I, Gacic Z, Paunovic M, Knezevic-Vukcevic J, Vukovic-Gacic B (2016) Assessment of the genotoxic potential along the Danube River by application of the comet assay on haemocytes of freshwater mussels: the Joint Danube Survey 3. Sci Total Environ 540:377–385

    Article  CAS  PubMed  Google Scholar 

  • Krishna G, Gopalakrishnan G, Goel S (2016) In vitro and in vivo genotoxicity assessment of the dopamine receptor antagonist molindone hydrochloride. Environ Mol Mutagen 57(4):288–298. doi:10.1002/em.22007

    Article  CAS  PubMed  Google Scholar 

  • Kruger K, Ziegler V, Hartmann C, Henninger C, Thomale J, Schupp N, Fritz G (2016) Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells. Toxicol Appl Pharmacol 292:103–114

    Article  PubMed  CAS  Google Scholar 

  • Kubasek J, Vojtech D, Jablonska E, Pospisilova I, Lipov J, Ruml T (2016) Structure, mechanical characteristics and in vitro degradation, cytotoxicity, genotoxicity and mutagenicity of novel biodegradable Zn–Mg alloys. Mater Sci Eng C Mater Biol Appl 58:24–35

    Article  CAS  PubMed  Google Scholar 

  • Kumaravel TS, Vilhar B, Faux SP, Jha AN (2009) Comet Assay measurements: a perspective. Cell Biol Toxicol 25:53–64

    Article  CAS  PubMed  Google Scholar 

  • Kumari M, Ghosh P, Thakur IS (2016) Landfill leachate treatment using bacto-algal co-culture: an integrated approach using chemical analyses and toxicological assessment. Ecotoxicol Environ Saf 128:44–51

    Article  CAS  PubMed  Google Scholar 

  • Kurashige T, Shimamura M, Nagayama Y (2016) Differences in quantification of DNA double-strand breaks assessed by 53BP1/gammaH2AX focus formation assays and the comet assay in mammalian cells treated with irradiation and N-acetyl-l-cysteine. J Radiat Res 57(3):312–317. doi:10.1093/jrr/rrw001

    Article  PubMed  PubMed Central  Google Scholar 

  • Kusrini E, Hashim F, Azmi WN, Amin NM, Estuningtyas A (2016) A novel antiamoebic agent against Acanthamoeba sp.—a causative agent for eye keratitis infection. Spectrochim Acta A Mol Biomol Spectrosc 153:714–721

    Article  CAS  PubMed  Google Scholar 

  • Lai SH, Li W, Yao JH, Han BJ, Jiang GB, Zhang C, Zeng CC, Liu YJ (2016) Protein binding and anticancer activity studies of ruthenium(II) polypyridyl complexes toward BEL-7402 cells. J Photochem Photobiol B 158:39–48

    Article  CAS  PubMed  Google Scholar 

  • Lan J, Gou N, Rahman SM, Gao C, He M, Gu AZ (2016) A quantitative toxicogenomics assay for high-throughput and mechanistic genotoxicity assessment and screening of environmental pollutants. Environ Sci Technol 50:3202–3214

    Article  CAS  PubMed  Google Scholar 

  • Lanier C, Manier N, Cuny D, Deram A (2015) The comet assay in higher terrestrial plant model: review and evolutionary trends. Environ Pollut 207:6–20

    Article  CAS  PubMed  Google Scholar 

  • Le Hégarat L, Takakura N, Simar S, Nesslany F, Fessard V (2014) The in vivo genotoxicity studies on nivalenol and deoxynivalenol. EFSA supporting publication EN-697:1–33. http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/697e.pdf. Accessed 28 June 2016

  • Li Y, Feng X, Du W, Li Y, Liu BF (2013) Ultrahigh-throughput approach for analyzing single-cell genomic damage with an agarose-based microfluidic comet array. Anal Chem 85:4066–4073

    Article  CAS  PubMed  Google Scholar 

  • Li Q, Chen L, Liu L, Wu L (2016a) Embryotoxicity and genotoxicity evaluation of sediments from Yangtze River estuary using zebrafish (Danio rerio) embryos. Environ Sci Pollut Res Int 23:4908–4918

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Hu G, Li P, Tang S, Zhang J, Jia G (2016b) miR-3940-5p enhances homologous recombination after DSB in Cr(VI) exposed 16HBE cell. Toxicology 344–346:1–6

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Wei L, Cao J, Qiu L, Jiang X, Li P, Song Q, Zhou H, Han Q, Diao X (2016c) Oxidative stress, DNA damage and antioxidant enzyme activities in the pacific white shrimp (Litopenaeus vannamei) when exposed to hypoxia and reoxygenation. Chemosphere 144:234–240

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Sun B, Wang X, Nie J, Chen Z, An Y, Tong J (2016a) Synergistic effect of radon and sodium arsenite on DNA damage in HBE cells. Environ Toxicol Pharmacol 41:127–131

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Liu H, Gao F, Dahlstrom KR, Sturgis EM, Wei Q (2016b) Reduced DNA double-strand break repair capacity and risk of squamous cell carcinoma of the head and neck—a case-control study. DNA Repair 40:18–26

    Article  CAS  PubMed  Google Scholar 

  • Lorenzo Y, Azqueta A, Luna L, Bonilla F, Dominguez G, Collins AR (2009) The carotenoid beta-cryptoxanthin stimulates the repair of DNA oxidation damage in addition to acting as an antioxidant in human cells. Carcinogenesis 30:308–314

    Article  CAS  PubMed  Google Scholar 

  • Lorenzo Y, Costa S, Collins AR, Azqueta A (2013) The comet assay, DNA damage, DNA repair and cytotoxicity: hedgehogs are not always dead. Mutagenesis 28:427–432

    Article  CAS  PubMed  Google Scholar 

  • Lovato FL, de Oliveira CR, Adedara IA, Barbisan F, Moreira KL, Dalberto M, da Rocha MI, Marroni NP, da Cruz IB, Costabeber IB (2016) Quercetin ameliorates polychlorinated biphenyls-induced testicular DNA damage in rats. Andrologia 48:51–58

    Article  CAS  PubMed  Google Scholar 

  • Lovell DP, Omori T (2008) Statistical issues in the use of the comet assay. Mutagenesis 23:171–182

    Article  CAS  PubMed  Google Scholar 

  • Lovreglio P, Doria D, Fracasso ME, Barbieri A, Sabatini L, Drago I, Violante FS, Soleo L (2016) DNA damage and repair capacity in workers exposed to low concentrations of benzene. Environ Mol Mutagen 57:151–158

    Article  CAS  PubMed  Google Scholar 

  • Lundqvist J, Hellman B, Oskarsson A (2016) Fungicide prochloraz induces oxidative stress and DNA damage in vitro. Food Chem Toxicol 91:36–41

    Article  CAS  PubMed  Google Scholar 

  • Ma T, Chen L, Wu L, Zhang H, Luo Y (2016) Oxidative stress, cytotoxicity and genotoxicity in earthworm Eisenia fetida at different di-n-butyl phthalate exposure levels. PLoS ONE 11:e0151128

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Machado CS, Venancio VP, Aissa AF, Hernandes LC, Mello MB, Lama JE, Marzocchi-Machado CM, Bianchi ML, Antunes LM (2016) Vitamin D3 deficiency increases DNA damage and the oxidative burst of neutrophils in a hypertensive rat model. Mutat Res Genet Toxicol Environ Mutagen 798–799:19–26

    Article  CAS  Google Scholar 

  • Magaye R, Gu Y, Wang Y, Su H, Zhou Q, Mao G, Shi H, Yue X, Zou B, Xu J, Zhao J (2016) In vitro and in vivo evaluation of the toxicities induced by metallic nickel nano and fine particles. J Mol Histol 47(3):273–286. doi:10.1007/s10735-016-9671-6

    Article  CAS  PubMed  Google Scholar 

  • Magdolenova Z, Collins A, Kumar A, Dhawan A, Stone V, Dusinska M (2014) Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology 8:233–278

    Article  CAS  PubMed  Google Scholar 

  • Martins M, Costa PM (2015) The comet assay in environmental risk assessment of marine pollutants: applications, assets and handicaps of surveying genotoxicity in non-model organisms. Mutagenesis 30:89–106

    Article  CAS  PubMed  Google Scholar 

  • Mavuluri J, Beesetti S, Surabhi R, Kremerskothen J, Venkatraman G, Rayala K (2016) Phosphorylation dependent regulation of DNA damage response of adaptor protein KIBRA in cancer cells. Mol Cell Biol 36(9):1354–1365. doi:10.1128/MCB.01004-15

    Article  CAS  PubMed  Google Scholar 

  • Menezes AP, da Silva J, Fisher C, da Silva FR, Reyes JM, Picada JN, Ferraz AG, Correa DS, Premoli SM, Dias JF, de Souza CT, Ferraz AB (2016) Chemical and toxicological effects of medicinal Baccharis trimera extract from coal burning area. Chemosphere 146:396–404

    Article  CAS  PubMed  Google Scholar 

  • Miloshev G, Mihaylov I, Anachkova B (2002) Application of the single cell gel electrophoresis on yeast cells. Mutat Res 513:69–74

    Article  CAS  PubMed  Google Scholar 

  • Miranda-Spooner M, Paccola CC, Neves FM, de Oliva SU, Miraglia SM (2016) Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation. Andrology 4:218–231

    Article  CAS  PubMed  Google Scholar 

  • Mitic-Culafic D, Nikolic B, Simin N, Jasnic N, Cetojevic-Simin D, Krstic M, Knezevic-Vukcevic J (2016) Effect of Allium flavum L. and Allium melanantherum Panc. Extracts on oxidative DNA damage and antioxidative enzymes superoxide dismutase and catalase. Plant Foods Hum Nutr 71:28–34

    Article  CAS  PubMed  Google Scholar 

  • Mladenov E, Magin S, Soni A, Iliakis G (2016) DNA double-strand-break repair in higher eukaryotes and its role in genomic instability and cancer: cell cycle and proliferation-dependent regulation. Semin Cancer Biol 37–38:51–64. doi:10.1016/j.semcancer.2016.03.003

    Article  PubMed  CAS  Google Scholar 

  • Mohamed HR, Hussien NA (2016) Genotoxicity studies of titanium dioxide nanoparticles (TiO2NPs) in the brain of mice. Scientifica 2016:6710840

    PubMed  PubMed Central  Google Scholar 

  • Moller P, Viscovich M, Lykkesfeldt J, Loft S, Jensen A, Poulsen HE (2004) Vitamin C supplementation decreases oxidative DNA damage in mononuclear blood cells of smokers. Eur J Nutr 43:267–274

    Article  CAS  PubMed  Google Scholar 

  • Moller P, Hemmingsen JG, Jensen DM, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M, Cao Y, Kermanizadeh A, Klingberg H, Christophersen DV, Hersoug LG, Loft S (2015) Applications of the comet assay in particle toxicology: air pollution and engineered nanomaterials exposure. Mutagenesis 30:67–83

    Article  PubMed  CAS  Google Scholar 

  • Moretti EG, Yujra VQ, Claudio SR, Silva MJ, Vilegas W, Pereira CD, de OF, Ribeiro DA (2016) Acute crack cocaine exposure induces genetic damage in multiple organs of rats. Environ Sci Pollut Res Int 23(8):8104–8112. doi:10.1007/s11356-016-6141-3

    Article  CAS  PubMed  Google Scholar 

  • Morsy GM, El-Ala KS, Ali AA (2016) Studies on fate and toxicity of nanoalumina in male albino rats: lethality, bioaccumulation and genotoxicity. Toxicol Ind Health 32:344–359

    Article  CAS  PubMed  Google Scholar 

  • Motohashi HH, Ishibashi H (2016) Cryopreservation of ovaries from neonatal marmoset monkeys. Exp Anim. http://doi.org/10.1538/expanim.15-0097

  • Munjal U, Scharlau D, Glei M (2012) Gut fermentation products of inulin-type fructans modulate the expression of xenobiotic-metabolising enzymes in human colonic tumour cells. Anticancer Res 32:5379–5386

    CAS  PubMed  Google Scholar 

  • Mustapha N, Zouiten A, Dridi D, Tahrani L, Zouiten D, Mosrati R, Cherif A, Chekir-Ghedira L, Mansour HB (2016) Comet assay with gill cells of Mytilus galloprovincialis end point tools for biomonitoring of water antibiotic contamination: biological treatment is a reliable process for detoxification. Toxicol Ind Health 32:686–693

    Article  CAS  PubMed  Google Scholar 

  • Na TY, Ka NL, Rhee H, Kyeong D, Kim MH, Seong JK, Park YN, Lee MO (2016) Interaction of hepatitis B virus X protein with PARP1 results in inhibition of DNA repair in hepatocellular carcinoma. Oncogene. doi:10.1038/onc.2016.82

    PubMed  Google Scholar 

  • Naidoo RN, Makwela MH, Chuturgoon A, Tiloke C, Ramkaran P, Phulukdaree A (2016) Petrol exposure and DNA integrity of peripheral lymphocytes. Int Arch Occup Environ Health 89(5):785–792. doi:10.1007/s00420-016-1116-8

    Article  CAS  PubMed  Google Scholar 

  • Nemmar A, Yuvaraju P, Beegam S, Yasin J, Kazzam EE, Ali BH (2016) Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely exposed to amorphous silica nanoparticles. Int J Nanomed 11:919–928

    Article  CAS  Google Scholar 

  • Niwa AM, D Epiro GF, Marques LA, Semprebon SC, Sartori D, Ribeiro LR, Mantovani MS (2016) Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells. Naunyn Schmiedebergs Arch Pharmacol 389(6):557–571. doi:10.1007/s00210-016-1225-7

    Article  CAS  PubMed  Google Scholar 

  • Novotnik B, Scancar J, Milacic R, Filipic M, Zegura B (2016) Cytotoxic and genotoxic potential of Cr(VI), Cr(III)-nitrate and Cr(III)-EDTA complex in human hepatoma (HepG2) cells. Chemosphere 154:124–131

    Article  CAS  PubMed  Google Scholar 

  • Nowak A, Czyzowska A, Huben K, Sojka M, Kuberski S, Otlewska A, Slizewska K (2016) Prebiotics and age, but not probiotics affect the transformation of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) by fecal microbiota—an in vitro study. Anaerobe 39:124–135. doi:10.1016/j.anaerobe.2016.03.009

    Article  CAS  PubMed  Google Scholar 

  • OECD (2014) OECD guideline for the testing of chemicals—in vivo mammalian alkaline Comet Assay. TG 489

  • Olive PL (1999) DNA damage and repair in individual cells: applications of the comet assay in radiobiology. Int J Radiat Biol 75:395–405

    Article  CAS  PubMed  Google Scholar 

  • Olive PL, Banath JP (2006) The comet assay: a method to measure DNA damage in individual cells. Nat Protoc 1:23–29

    Article  CAS  PubMed  Google Scholar 

  • Olive PL, Banath JP, Durand RE (1990) Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the “comet” assay. Radiat Res 122:86–94

    Article  CAS  PubMed  Google Scholar 

  • Ostling O, Johanson KJ (1984) Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem Biophys Res Commun 123:291–298

    Article  CAS  PubMed  Google Scholar 

  • Ozcagli E, Alpertunga B, Fenga C, Berktas M, Tsitsimpikou C, Wilks MF, Tsatsakis A (2016) Effects of 3-monochloropropane-1,2-diol (3-MCPD) and its metabolites on DNA damage and repair under in vitro conditions. Food Chem Toxicol 89:1–7

    Article  CAS  PubMed  Google Scholar 

  • Pahlke G, Tiessen C, Domnanich K, Kahle N, Groh IA, Schreck I, Weiss C, Marko D (2016) Impact of Alternaria toxins on CYP1A1 expression in different human tumor cells and relevance for genotoxicity. Toxicol Lett 240:93–104

    Article  CAS  PubMed  Google Scholar 

  • Panzarino O, Hyrsl P, Dobes P, Vojtek L, Vernile P, Bari G, Terzano R, Spagnuolo M, de Lillo E (2016) Rank-based biomarker index to assess cadmium ecotoxicity on the earthworm Eisenia andrei. Chemosphere 145:480–486

    Article  CAS  PubMed  Google Scholar 

  • Papa M, Ceretti E, Viola GCV, Feretti D, Zerbini I, Mazzoleni G, Steimberg N, Pedrazzani R, Bertanza G (2016) The assessment of WWTP performance: towards a jigsaw puzzle evaluation? Chemosphere 145:291–300

    Article  CAS  PubMed  Google Scholar 

  • Park S, Choi S, Ahn B (2016) DNA strand breaks in mitotic germ cells of caenorhabditis elegans evaluated by Comet Assay. Mol Cells 39:204–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patar A, Giri A, Boro F, Bhuyan K, Singha U, Giri S (2016) Cadmium pollution and amphibians—studies in tadpoles of Rana limnocharis. Chemosphere 144:1043–1049

    Article  CAS  PubMed  Google Scholar 

  • Patnaik R, Padhy RN (2016) Evaluation of geno-toxicity of methyl parathion and chlorpyrifos to human liver carcinoma cell line (HepG2). Environ Sci Pollut Res Int 23(9):8492–8499. doi: 10.1007/s11356-015-5963-8

    Article  CAS  PubMed  Google Scholar 

  • Pedro DF, Ramos AA, Lima CF, Baltazar F, Pereira-Wilson C (2016) Colon cancer chemoprevention by sage tea drinking: decreased DNA damage and cell proliferation. Phytother Res 30:298–305

    Article  CAS  PubMed  Google Scholar 

  • Peteffi GP, Antunes MV, Carrer C, Valandro ET, Santos S, Glaeser J, Mattos L, da Silva LB, Linden R (2016) Environmental and biological monitoring of occupational formaldehyde exposure resulting from the use of products for hair straightening. Environ Sci Pollut Res Int 23:908–917

    Article  CAS  PubMed  Google Scholar 

  • Petrovic J, Stanic D, Dmitrasinovic G, Plecas-Solarovic B, Ignjatovic S, Batinic B, Popovic D, Pesic V (2016) Magnesium supplementation diminishes peripheral blood lymphocyte DNA oxidative damage in athletes and sedentary young man. Oxid Med Cell Longev 2016:2019643

    Article  PubMed  PubMed Central  Google Scholar 

  • Peycheva E, Alexandrova R, Miloshev G (2014) Application of the yeast comet assay in testing of food additives for genotoxicity. LWT Food Sci Technol 59:510–517

    Article  CAS  Google Scholar 

  • Phark S, Park SY, Chang YS, Choi S, Lim JY, Kim Y, Seo JB, Jung WW, Sul D (2016) Evaluation of toxicological biomarkers in secreted proteins of HepG2 cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and their expressions in the plasma of rats and incineration workers. Biochim Biophys Acta 1864:584–593

    Article  CAS  PubMed  Google Scholar 

  • Poletta GL, Simoniello MF, Mudry MD (2016) Biomarkers of oxidative damage and antioxidant defense capacity in Caiman latirostris blood. Comp Biochem Physiol C Toxicol Pharmacol 179:29–36

    Article  CAS  PubMed  Google Scholar 

  • Pourrut B, Pinelli E, Mendiola VC, Silvestre J, Douay F (2015) Recommendations for increasing alkaline comet assay reliability in plants. Mutagenesis 30:37–43

    Article  CAS  PubMed  Google Scholar 

  • Ramos AA, Castro-Carvalho B, Prata-Sena M, Dethoup T, Buttachon S, Kijjoa A, Rocha E (2016) Crude extracts of marine-derived and soil fungi of the genus Neosartorya exhibit selective anticancer activity by inducing cell death in colon, breast and skin cancer cell lines. Pharmacogn Res 8:8–15

    Article  Google Scholar 

  • Raphael S, Aude J, Olivier P, Melissa PL, Aurelien B, Christophe B, Jean MP, Sylvie B, Alain D, Wilfried S (2016) Characterization of a genotoxicity biomarker in three-spined stickleback (Gasterosteus aculeatus L.): biotic variability and integration in a battery of biomarkers for environmental monitoring. Environ Toxicol 31:415–426

    Article  CAS  Google Scholar 

  • Ristow M (2014) Unraveling the truth about antioxidants: mitohormesis explains ROS-induced health benefits. Nat Med 20:709–711

    Article  CAS  PubMed  Google Scholar 

  • Ristow M, Schmeisser K (2014) Mitohormesis: promoting health and lifespan by increased levels of reactive oxygen species (ROS). Dose Response 12:288–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberto MM, Matsumoto ST, Jamal CM, Malaspina O, Marin-Morales MA (2016) Evaluation of the genotoxicity/mutagenicity and antigenotoxicity/antimutagenicity induced by propolis and Baccharis dracunculifolia, by in vitro study with HTC cells. Toxicol In Vitro 33:9–15

    Article  CAS  PubMed  Google Scholar 

  • Roberts DJ, McKeon M, Xu Y, Stankowski LF Jr (2016) Comparison of integrated genotoxicity endpoints in rats after acute and subchronic oral doses of 4-nitroquinoline-1-oxide. Environ Mol Mutagen 57:17–27

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues S, Antunes SC, Correia AT, Nunes B (2016) Acute and chronic effects of erythromycin exposure on oxidative stress and genotoxicity parameters of Oncorhynchus mykiss. Sci Total Environ 545–546:591–600

    Article  PubMed  CAS  Google Scholar 

  • Rojas E, Lorenzo Y, Haug K, Nicolaissen B, Valverde M (2014) Epithelial cells as alternative human biomatrices for comet assay. Front Genet 5:386

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Roos WP, Thomas AD, Kaina B (2016) DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer 16:20–33

    Article  CAS  PubMed  Google Scholar 

  • Rosignoli P, Fuccelli R, Sepporta MV, Fabiani R (2016) In vitro chemo-preventive activities of hydroxytyrosol: the main phenolic compound present in extra-virgin olive oil. Food Funct 7:301–307

    Article  CAS  PubMed  Google Scholar 

  • Roy P, Mukherjee A, Giri S (2016) Evaluation of genetic damage in tobacco and arsenic exposed population of Southern Assam, India using buccal Cytome Assay and Comet Assay. Ecotoxicol Environ Saf 124:169–176

    Article  CAS  PubMed  Google Scholar 

  • Rubio L, Annangi B, Vila L, Hernandez A, Marcos R (2016) Antioxidant and anti-genotoxic properties of cerium oxide nanoparticles in a pulmonary-like cell system. Arch Toxicol 90:269–278

    Article  CAS  PubMed  Google Scholar 

  • Santos CL, Pourrut B, Ferreira de Oliveira JM (2015) The use of comet assay in plant toxicology: recent advances. Front Genet 6:216

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Saquib Q, Siddiqui MA, Ahmed J, Al-Salim A, Ansari SM, Faisal M, Al-Khedhairy AA, Musarrat J, Alwathnani HA, Alatar AA, Al-Arifi SA (2016) Hazards of low dose flame-retardants (BDE-47 and BDE-32): influence on transcriptome regulation and cell death in human liver cells. J Hazard Mater 308:37–49

    Article  CAS  PubMed  Google Scholar 

  • Sasidharan A, Swaroop S, Chandran P, Nair S, Koyakutty M (2016) Cellular and molecular mechanistic insight into the DNA-damaging potential of few-layer graphene in human primary endothelial cells. Nanomedicine 12(5):1347–1355. doi:10.1016/j.nano.2016.01.014

    CAS  PubMed  Google Scholar 

  • Sassi A, Bouhlel I, Mustapha N, Mokdad-Bzeouich I, Chaabane F, Ghedira K, Chekir-Ghedira L (2016) Assessment in vitro of the genotoxicity, antigenotoxicity and antioxidant of Ceratonia siliqua L. extracts in murine leukaemia cells L1210 by Comet Assay. Regul Toxicol Pharmacol 77:117–124

    Article  CAS  PubMed  Google Scholar 

  • Savina NV, Nikitchenko NV, Kuzhir TD, Rolevich AI, Krasny SA, Goncharova RI (2016) The cellular response to oxidatively induced DNA damage and polymorphism of some DNA repair genes associated with clinicopathological features of bladder cancer. Oxid Med Cell Longev 2016:5710403

    Article  PubMed  Google Scholar 

  • Schiavo S, Oliviero M, Miglietta M, Rametta G, Manzo S (2016) Genotoxic and cytotoxic effects of ZnO nanoparticles for Dunaliella tertiolecta and comparison with SiO2 and TiO2 effects at population growth inhibition levels. Sci Total Environ 550:619–627

    Article  CAS  PubMed  Google Scholar 

  • Shaposhnikov S, Azqueta A, Henriksson S, Meier S, Gaivao I, Huskisson NH, Smart A, Brunborg G, Nilsson M, Collins AR (2010) Twelve-gel slide format optimised for comet assay and fluorescent in situ hybridisation. Toxicol Lett 195:31–34

    Article  CAS  PubMed  Google Scholar 

  • Shaposhnikov S, Thomsen PD, Collins AR (2011) Combining fluorescent in situ hybridization with the comet assay for targeted examination of DNA damage and repair. Methods Mol Biol 682:115–132

    Article  CAS  PubMed  Google Scholar 

  • Sharif A, Ashraf M, Anjum AA, Javeed A, Altaf I, Akhtar MF, Abbas M, Akhtar B, Saleem A (2016) Pharmaceutical wastewater being composite mixture of environmental pollutants may be associated with mutagenicity and genotoxicity. Environ Sci Pollut Res Int 23:2813–2820

    Article  CAS  PubMed  Google Scholar 

  • Sharma K, Kumar A, Chandna S (2016) Constitutive hyperactivity of histone deacetylases enhances radioresistance in Lepidopteran Sf9 insect cells. Biochim Biophys Acta 1860:1237–1246

    Article  CAS  PubMed  Google Scholar 

  • Shen M, Bin P, Li H, Zhang X, Sun X, Duan H, Niu Y, Meng T, Dai Y, Gao W, Yu S, Gu G, Zheng Y (2016) Increased levels of etheno-DNA adducts and genotoxicity biomarkers of long-term exposure to pure diesel engine exhaust. Sci Total Environ 543:267–273

    Article  CAS  PubMed  Google Scholar 

  • Simonato JD, Mela M, Doria HB, Guiloski IC, Randi MA, Carvalho PS, Meletti PC, Silva de Assis HC, Bianchini A, Martinez CB (2016) Biomarkers of waterborne copper exposure in the Neotropical fish Prochilodus lineatus. Aquat Toxicol 170:31–41

    Article  CAS  PubMed  Google Scholar 

  • Simonyan A, Gabrielyan B, Minasyan S, Hovhannisyan G, Aroutiounian R (2016) Genotoxicity of water contaminants from the Basin of Lake Sevan, Armenia evaluated by the Comet Assay in Gibel Carp (Carassius auratus gibelio) and tradescantia bioassays. Bull Environ Contam Toxicol 96:309–313

    Article  CAS  PubMed  Google Scholar 

  • Singh NP (2016) The comet assay: reflections on its development, evolution and applications. Mutat Res Rev Mutat Res 767:23–30

    Article  CAS  PubMed  Google Scholar 

  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    Article  CAS  PubMed  Google Scholar 

  • Skipper A, Sims JN, Yedjou CG, Tchounwou PB (2016) Cadmium chloride induces DNA damage and apoptosis of human liver carcinoma cells via oxidative stress. Int J Environ Res Public Health 13(1):88. doi:10.3390/ijerph13010088

    Article  PubMed Central  Google Scholar 

  • Slizewska K, Nowak A, Smulikowska S (2016) Probiotic preparation reduces faecal water genotoxicity and cytotoxicity in chickens fed ochratoxin A contaminated feed (in vivo study). Acta Biochim Pol 63(2):281–286. doi:10.18388/abp.2015_1094

    Article  PubMed  Google Scholar 

  • Slyskova J, Korenkova V, Collins AR, Prochazka P, Vodickova L, Svec J, Lipska L, Levy M, Schneiderova M, Liska V, Holubec L, Kumar R, Soucek P, Naccarati A, Vodicka P (2012) Functional, genetic, and epigenetic aspects of base and nucleotide excision repair in colorectal carcinomas. Clin Cancer Res 18:5878–5887

    Article  CAS  PubMed  Google Scholar 

  • Smith AJ, Ball SS, Bowater RP, Wormstone IM (2016) PARP-1 inhibition influences the oxidative stress response of the human lens. Redox Biol 8:354–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soloneski S, Nikoloff N, Larramendy ML (2016) Analysis of possible genotoxicity of the herbicide flurochloridone and its commercial formulations: endo III and Fpg alkaline comet assays in Chinese hamster ovary (CHO-K1) cells. Mutat Res, Genet Toxicol Environ Mutagen 797:46–52

    Article  CAS  Google Scholar 

  • Souza TA, Franchi LP, Rosa LR, da Veiga MA, Takahashi CS (2016) Cytotoxicity and genotoxicity of silver nanoparticles of different sizes in CHO-K1 and CHO-XRS5 cell lines. Mutat Res Genet Toxicol Environ Mutagen 795:70–83

    Article  CAS  PubMed  Google Scholar 

  • Speit G, Hartmann A (2005) The comet assay: a sensitive genotoxicity test for the detection of DNA damage. Methods Mol Biol 291:85–95

    CAS  PubMed  Google Scholar 

  • Sunjog K, Kolarevic S, Kracun-Kolarevic M, Visnjic-Jeftic Z, Skoric S, Gacic Z, Lenhardt M, Vasic N, Vukovic-Gacic B (2016) Assessment of status of three water bodies in Serbia based on tissue metal and metalloid concentration (ICP-OES) and genotoxicity (comet assay). Environ Pollut 213:600–607

    Article  CAS  PubMed  Google Scholar 

  • Sutris JM, How V, Sumeri SA, Muhammad M, Sardi D, Mohd Mokhtar MT, Muhammad H, Ghazi HF, Isa ZM (2016) Genotoxicity following organophosphate pesticides exposure among orang asli children living in an agricultural island in Kuala Langat, Selangor, Malaysia. Int J Occup Environ Med 7:42–51

    CAS  PubMed  Google Scholar 

  • Tabei Y, Sonoda A, Nakajima Y, Biju V, Makita Y, Yoshida Y, Horie M (2016) Intracellular accumulation of indium ions released from nanoparticles induces oxidative stress, proinflammatory response and DNA damage. J Biochem 159:225–237

    Article  CAS  PubMed  Google Scholar 

  • Tarnow P, Hutzler C, Grabiger S, Schon K, Tralau T, Luch A (2016) Estrogenic activity of mineral oil aromatic hydrocarbons used in printing inks. PLoS One 11:e0147239

  • Tekiner IH, Mutlu H, Algingil S, Dincerler E (2015) Considerations for nanosciences in food science and nutrition: enhanced food properties. Recent Pat Food Nutr Agric 7:3–8

    Article  PubMed  Google Scholar 

  • Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221

    Article  CAS  PubMed  Google Scholar 

  • Toufexi E, Dailianis S, Vlastos D, Manariotis ID (2016) Mediated effect of ultrasound treated Diclofenac on mussel hemocytes: first evidence for the involvement of respiratory burst enzymes in the induction of DCF-mediated unspecific mode of action. Aquat Toxicol 175:144–153

    Article  CAS  PubMed  Google Scholar 

  • Tugrul S, Kocyigit A, Dogan R, Eren SB, Senturk E, Ozturan O, Ozar OF (2016) Total antioxidant status and oxidative stress in recurrent aphthous stomatitis. Int J Dermatol 55:e130–e135

    Article  CAS  PubMed  Google Scholar 

  • Uboldi C, Orsiere T, Darolles C, Aloin V, Tassistro V, George I, Malard V (2016) Poorly soluble cobalt oxide particles trigger genotoxicity via multiple pathways. Part Fibre Toxicol 13:5

    Article  PubMed  PubMed Central  Google Scholar 

  • Uthaman S, Lee SJ, Cherukula K, Cho CS, Park IK (2015) Polysaccharide-coated magnetic nanoparticles for imaging and gene therapy. Biomed Res Int 2015:959175

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Valencak TG, Raith J, Staniek K, Gille L, Strasser A (2016) Lactation affects isolated mitochondria and its fatty acid composition but has no effect on tissue protein oxidation, lipid peroxidation or DNA-damage in laboratory mice. Antioxidants 5(1):2. doi:10.3390/antiox5010002

    Article  PubMed Central  CAS  Google Scholar 

  • Valverde M, Rojas E (2009) Environmental and occupational biomonitoring using the Comet assay. Mutat Res 681:93–109

    Article  CAS  PubMed  Google Scholar 

  • Vande Loock K, Decordier I, Ciardelli R, Haumont D, Kirsch-Volders M (2010) An aphidicolin-block nucleotide excision repair assay measuring DNA incision and repair capacity. Mutagenesis 25:25–32

    Article  CAS  PubMed  Google Scholar 

  • Velali E, Papachristou E, Pantazaki A, Choli-Papadopoulou T, Planou S, Kouras A, Manoli E, Besis A, Voutsa D, Samara C (2016) Redox activity and in vitro bioactivity of the water-soluble fraction of urban particulate matter in relation to particle size and chemical composition. Environ Pollut 208:774–786

    Article  CAS  PubMed  Google Scholar 

  • Venkatesh P, Panyutin IV, Remeeva E, Neumann RD, Panyutin IG (2016) Effect of chromatin structure on the extent and distribution of DNA double strand breaks produced by ionizing radiation; comparative study of hESC and differentiated cells lines. Int J Mol Sci 17(1):58. doi:10.3390/ijms17010058

    Article  PubMed Central  Google Scholar 

  • Ventura L, Giovannini A, Savio M, Dona M, Macovei A, Buttafava A, Carbonera D, Balestrazzi A (2013) Single cell gel electrophoresis (Comet) assay with plants: research on DNA repair and ecogenotoxicity testing. Chemosphere 92:1–9

    Article  CAS  PubMed  Google Scholar 

  • Veronez AC, Salla RV, Baroni VD, Barcarolli IF, Bianchini A, Dos Reis Martinez CB, Chippari-Gomes AR (2016) Genetic and biochemical effects induced by iron ore, Fe and Mn exposure in tadpoles of the bullfrog Lithobates catesbeianus. Aquat Toxicol 174:101–108

    Article  CAS  PubMed  Google Scholar 

  • Vilfan ID, Conwell CC, Hud NV (2004) Formation of native-like mammalian sperm cell chromatin with folded bull protamine. J Biol Chem 279:20088–20095

    Article  CAS  PubMed  Google Scholar 

  • Viswanathan S, Manisankar P (2015) Nanomaterials for electrochemical sensing and decontamination of pesticides. J Nanosci Nanotechnol 15:6914–6923

    Article  CAS  PubMed  Google Scholar 

  • Wang G, Lu G, Yin P, Zhao L, Jimmy YQ (2016a) Genotoxicity assessment of membrane concentrates of landfill leachate treated with Fenton reagent and UV-Fenton reagent using human hepatoma cell line. J Hazard Mater 307:154–162

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Wang J, Wang G, Zhu L, Wang J (2016b) DNA damage and oxidative stress induced by imidacloprid exposure in the earthworm Eisenia fetida. Chemosphere 144:510–517

    Article  CAS  PubMed  Google Scholar 

  • Wang P, Lombi E, Zhao FJ, Kopittke PM (2016c) Nanotechnology: a new opportunity in plant sciences. Trends Plant Sci. doi:10.1016/j.tplants.2016.04.005

    PubMed  Google Scholar 

  • Watson C, Ge J, Cohen J, Pyrgiotakis G, Engelward BP, Demokritou P (2014) High-throughput screening platform for engineered nanoparticle-mediated genotoxicity using CometChip technology. ACS Nano 8:2118–2133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilczek G, Medrzak M, Augustyniak M, Wilczek P, Stalmach M (2016) Genotoxic effects of starvation and dimethoate in haemocytes and midgut gland cells of wolf spider Xerolycosa nemoralis (Lycosidae). Environ Pollut 213:370–378

    Article  CAS  PubMed  Google Scholar 

  • Will O, Gocke E, Eckert I, Schulz I, Pflaum M, Mahler HC, Epe B (1999) Oxidative DNA damage and mutations induced by a polar photosensitizer, Ro19-8022. Mutat Res 435:89–101

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Zhang L, Yang C, Zong M, Huang Q, Tao L (2016) Detection on emamectin benzoate-induced apoptosis and DNA damage in Spodoptera frugiperda Sf-9 cell line. Pestic Biochem Physiol 126:6–12

    Article  CAS  PubMed  Google Scholar 

  • Xu Z, Shao J, Li L, Peng X, Chen M, Li G, Yan H, Yang B, Luo P, He Q (2016) All-trans retinoic acid synergizes with topotecan to suppress AML cells via promoting RARalpha-mediated DNA damage. BMC Cancer 16:2

    Article  PubMed  PubMed Central  Google Scholar 

  • Yahia D, Haruka I, Kagashi Y, Tsuda S (2016) 8-Hydroxy-2′-deoxyguanosine as a biomarker of oxidative DNA damage induced by perfluorinated compounds in TK6 cells. Environ Toxicol 31:192–200

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Yuan Y, Fu C, Xu X, Zhou J, Wang S, Kong L, Li Z, Guo Q, Wei L (2016a) LZ-106, a novel analog of enoxacin, inducing apoptosis via activation of ROS-dependent DNA damage response in NSCLCs. Free Radic Biol Med 95:155–168

    Article  CAS  PubMed  Google Scholar 

  • Yang SM, Tsai KD, Wong HY, Liu YH, Chen TW, Cherng J, Hsu KC, Ang YU, Cherng JM (2016b) Molecular mechanism of Cinnamomum verum component cuminaldehyde inhibits cell growth and induces cell death in human lung squamous cell carcinoma NCI-H520 cells in vitro and in vivo. J Cancer 7:251–261

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Ji F, Cui Y, Li M (2016c) Ecotoxicological effects of earthworm following long-term Dechlorane Plus exposure. Chemosphere 144:2476–2481

    Article  CAS  PubMed  Google Scholar 

  • Yilmaz S, Ustundag A, Cemiloglu UO, Duydu Y (2016) Protective effect of boric acid on oxidative DNA damage in chinese hamster lung fibroblast V79 cell lines. Cell J 17:748–754

    PubMed  PubMed Central  Google Scholar 

  • Yu V, Rahimy M, Korrapati A, Xuan Y, Zou AE, Krishnan AR, Tsui T, Aguilera JA, Advani S, Crotty Alexander LE, Brumund KT, Wang-Rodriguez J, Ongkeko WM (2016) Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Oral Oncol 52:58–65

    Article  CAS  PubMed  Google Scholar 

  • Zapata LM, Bock BC, Orozco LY, Palacio JA (2016) Application of the micronucleus test and comet assay in Trachemys callirostris erythrocytes as a model for in situ genotoxic monitoring. Ecotoxicol Environ Saf 127:108–116

    Article  CAS  PubMed  Google Scholar 

  • Zeeshan M, Murugadas A, Ghaskadbi S, Rajendran RB, Akbarsha MA (2016) ROS dependent copper toxicity in Hydra-biochemical and molecular study. Comp Biochem Physiol C Toxicol Pharmacol 185–186:1–12

    Article  PubMed  CAS  Google Scholar 

  • Zeng F, Sherry JP, Bols NC (2016) Use of the rainbow trout cell lines, RTgill-W1 and RTL-W1 to evaluate the toxic potential of benzotriazoles. Ecotoxicol Environ Saf 124:315–323

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Han BJ, Zeng CC, Lai SH, Li W, Tang B, Wan D, Jiang GB, Liu YJ (2016a) Synthesis, characterization, in vitro cytotoxicity and anticancer effects of ruthenium(II) complexes on BEL-7402 cells. J Inorg Biochem 157:62–72

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Cheng X, Gao Y, Bao J, Guan H, Lu R, Yu H, Xu Q, Sun Y (2016b) Induction of ROS-independent DNA damage by curcumin leads to G2/M cell cycle arrest and apoptosis in human papillary thyroid carcinoma BCPAP cells. Food Funct 7:315–325

    Article  CAS  PubMed  Google Scholar 

  • Zhao D, Shah NP (2016) Synergistic application of black tea extracts and lactic acid bacteria in protecting human colonocytes against oxidative damage. J Agric Food Chem 64:2238–2246

    Article  CAS  PubMed  Google Scholar 

  • Zhen N, Yang Q, Wu Q, Zhu X, Wang Y, Sun F, Mei W, Yu Y (2016) A novelly synthesized phenanthroline derivative is a promising DNA-damaging anticancer agent inhibiting G1/S checkpoint transition and inducing cell apoptosis in cancer cells. Cancer Chemother Pharmacol 77:169–180

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nutritional Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Straße 24, 07743, Jena, Germany

    M. Glei, T. Schneider & W. Schlörmann

Authors
  1. M. Glei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Schlörmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Glei.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 192 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Glei, M., Schneider, T. & Schlörmann, W. Comet assay: an essential tool in toxicological research. Arch Toxicol 90, 2315–2336 (2016). https://doi.org/10.1007/s00204-016-1767-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-016-1767-y

Keywords

Search

Navigation