Objective: Nowadays, much attention has been focused on the search for new non-invasive methodologies able to predict malignant transformation of oral mucosa cells. The aim of the present study was to comparatively evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated oral mucosa cells from smokers and non-smokers in buccal mucosa cells. Study Design: A total of 24 young, healthy smokers and 14 non-smokers were included in this setting. Individuals had epithelial cells from the cheek mechanically exfoliated, placed in fixative and dropped in clean slides which were checked for the above nuclear phenotypes. Results: Smokers presented more (p < 0.05) micronucleated oral mucosa cells than non-smokers. Tobacco smoke was not able to increase other nuclear alterations closely related to cytotoxicity such as karyorrhexis, pyknosis and karyolysis. Conclusion: In summary, these data indicate that the cigarette is able to induce micronuclei in oral mucosa cells, so the micronucleus test is a suitable method for predicting oral cancer risk.

1.
Nanjappa V, Renuse S, Sathe GJ, Raja R, Syed N, Radhakrishnan A, Subbannayya T, Patil A, Marimuthu A, Sahasrabuddhe NA, Guerrero-Preston R, Somani BL, Nair B, Kundu GC, Prasad TS, Califano JA, Gowda H, Sidransky D, Pandey A, Chatterjee A: Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes. Cancer Biol Ther 2015;16:1593-1603.
2.
Sanner T, Grimsrud TK: Nicotine: carcinogenicity and effects on response to cancer treatment - a review. Front Oncol 2015;5:196.
3.
Fenech M, Kirsch-Volders M, Natarajan AT, Surralles J, Crott JW, Parry J, Norppa H, Eastmond DA, Tucker JD, Thomas P: Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis 2011;26:125-132.
4.
Beliën JA, Copper MP, Braakhuis BJ, Snow GB, Baak JP: Standardization of counting micronuclei: definition of a protocol to measure genotoxic damage in human exfoliated cells. Carcinogenesis 1995;16:2395-2400.
5.
Tolbert PE, Shy CM, Allen JW: Micronuclei and other nuclear anomalies in buccal smears: methods development. Mutat Res 1992;271:69-77.
6.
Nersesyan A, Muradyan R, Kundi M, Knasmueller S: Impact of smoking on the frequencies of micronuclei and other nuclear abnormalities in exfoliated oral cells: a comparative study with different cigarette types. Mutagenesis 2011;26:295-3011.
7.
Bloching M, Hofmann A, Lautenschlager C, Berghaus A, Grummt T: Exfoliative cytology of normal buccal mucosa to predict the relative risk of cancer in the upper aerodigestive tract using the MN-assay. Oral Oncol 2000;36:550-555.
8.
Stich HF, Rosin MP: Quantitating the synergistic effect of smoking and alcohol consumption with the micronucleus test on human buccal mucosa cells. Int J Cancer 1983;31:305-308.
9.
Suhas S, Ganapathy KS, Gayatri Devi M, Ramesh C: Application of the micronucleus test to exfoliated epithelial cells from the oral cavity of beedi smokers, a high-risk group for oral cancer. Mutat Res 2004;561:15-21.
10.
Wu PA, Loh CH, Hsieh LL, Liu TY, Chen CJ, Liou SH: Clastogenic effect for cigarette smoking but not areca quid chewing as measured by micronuclei in exfoliated buccal mucosal cells. Mutat Res 2004;562:27-38.
11.
Kayal JJ, Trivedi AH, Dave BJ: Incidence of micronuclei in oral mucosa of users of tobacco products singly or in various combinations. Mutagenesis 1993;8:31-33.
12.
Motgi AA, Chavan MS, Diwan NN, Chowdhery A, Channe PP, Shete MVA: Assessment of cytogenic damage in the form of micronuclei in oral epithelial cells in patients using smokeless and smoked form of tobacco and non-tobacco users and its relevance for oral cancer. J Cancer Res Ther 2014;10:165-170.
13.
Ribeiro DA, Sannomiya EK, Pozzi R, Miranda SR, Angelieri F: Cellular death but not genetic damage in oral mucosa cells after exposure to digital lateral radiography. Clin Oral Investig 2011;15:357-360.
14.
Angelieri F, de Cássia Gonçalves Moleirinho T, Carlin V, Oshima CT, Ribeiro DA: Biomonitoring of oral epithelial cells in smokers and non-smokers submitted to panoramic X-ray: comparison between buccal mucosa and lateral border of the tongue. Clin Oral Investig 2010;14:669-674.
15.
International Agency for Research on Cancer: Tobacco Smoke and Involuntary Smoking. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Lyon, IARC, 2004, vol 83.
16.
Cairns J: Mutation selection and the natural history of cancer. Nature 1975;255:197-200.
17.
Stich HF, Stich W, Parida BB: Elevated frequency of micronucleated cells in the buccal mucosa of individuals at high risk for oral cancer: betel quid chewers. Cancer Lett 1982;17:125-134.
18.
Martins RA, Gomes GA, Aguiar O Jr, Ribeiro DA: Biomonitoring of oral epithelial cells in petrol station attendants: comparison between buccal mucosa and lateral border of the tongue. Environ Int 2009;35:1062-1065.
19.
Pereira CAB: Teste estatístico para comparar proporções em problemas de citogenética; in Rabelo-Gay N, Rodrigues MA, Monteleone-Neto R (eds): Mutagênese, Teratogênese e Carcinogênese (in Portuguese). São Paulo, Sociedade Brasileira de Genética, 1991, pp 113-121.
20.
Neri M, Fucic A, Knudsen LE, Lando C, Merlo F, Bonassi S: Micronuclei frequency in children exposed to environmental mutagens: a review. Mutat Res 2003;544:243-225.
21.
Thomas P, Harvey S, Gruner T, Fenech M: The buccal cytome and micronucleus frequency is substantially altered in Down's syndrome and normal ageing compared to young healthy controls. Mutat Res 2008;638:3-47.
22.
Kujan O, Oliver RJ, Khattab A, Roberts SA, Thakker N, Sloan A: Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol 2006;42:987-993.
23.
Sugano N, Minigeshi T, Kawamoto K, Ito K: Nicotine inhibits UV-induced activation of the apoptotic pathway. Toxicol Lett 2001;125:61-65.
24.
Burgaz S, Işcan A, Büyükbingöl ZK, Bozkurt A, Karakaya AE: Evaluation of micronuclei in exfoliated urothelial cells and urinary thioether excretion of smokers. Mutat Res 1995;335:163-116.
25.
Argentin G, Cicchetti R: Genotoxic and antiapoptotic effect of nicotine on human gingival fibroblasts. Toxicol Sci 2004;79:75-81.
26.
Murphy SE, Heiblum R: Effect of nicotine and tobacco-specific nitrosamines on the metabolism of N′-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by rat oral tissue. Carcinogenesis 1990;11:1663-1666.
27.
Richter E, Tricker AR: Nicotine inhibits the metabolic activation of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats. Carcinogenesis 1994;15:1061-1064.
28.
Weber RP, Coon JM, Triolo AJ: Nicotine inhibition of the metabolism of 3,4-benzopyrene, a carcinogen in tobacco smoke. Science 1974;184:1081-1083.
29.
Chen J, Higby R, Tian D, Tan D, Johnson MD, Xiao Y, Kellar KJ, Feng S, Shields PG: Toxicological analysis of low-nicotine and nicotine-free cigarettes. Toxicology 2008;249:194-203.
30.
Chen H, Liao K, Cui-Zhao L, Qiang-Wen F, Feng-Zeng X, Ping-Wu F, Liang-Guo S, Juan-Chen Y: Cigarette smoke extract induces apoptosis of rat alveolar type II cells via the PLTP/TGF-β1/Smad2 pathway. Int Immunopharmacol 2015;28:707-714.
31.
Liu Q, Tao Y, Zhao B: ESR study on scavenging effect of nicotine on free radicals. Appl Magn Reson 2003;24:105-112.
32.
Soto-Otero R, Mendez-Alvarez E, Hermida-Ameijeiras A, Lopez-Real M, Labandeira-Garcia JL: Effects of (-)-nicotine and (-)-cotinine on 6-hydroxydopamine-induced oxidative stress and neuro-toxicity: relevance for Parkinson's disease. Biochem Pharmacol 2002;64:125-135.
33.
Moler P, Knudsen LE, Loft H, Walin H: The comet assay as a rapid test in biomonitoring occupational exposure to DNA-damaging agents and effect of confounding factors. Cancer Epidemiol Biomarkers Prev 2000;9:1005-1015.
34.
Jones KH, York TP, Jackson-Cook C: Mechanisms leading to the formation of micronuclei containing sex chromosomes differ with age. Mutat Res 2012;18;747:207-217.
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