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Assessment of genotoxicity associated with Behcet’s disease using sister-chromatid exchange assay: vitamin E versus mitomycin C

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Abstract

Behcet’s disease (BD) is a multisystemic chronic inflammatory disorder that presents throughout the world with high frequency in Turkey and Middle East. BD has been shown to be associated with genotoxicity as patients with the disease have demonstrated high rates of sister chromatid exchange (SCE) and oxidative DNA damage. In this study, we examined the effect of vitamin E, which is known for its strong antioxidant activity, on the rate of SCE in cultured lymphocytes obtained from BD patients. In addition, the susceptibility of patient lymphocytes to the mutagenic agent mitomycin C (MMC) was also investigated. The results showed significant elevation in the rate of SCE in lymphocytes obtained from patients compared to those from healthy subjects (P < 0.01). Treatment with vitamin E normalized the elevated rate of SCE to a comparable level observed in the control group (P < 0.01). Finally, treatment of cultures with MMC significantly increased the rate of SCE in the lymphocytes of both patients and controls (P < 0.001). The magnitude of change in the rate of SCE induced by MMC was equivalent in both groups. This result suggests similar sensitivity of BD lymphocytes and control ones to MMC. In conclusion, genotoxicity associated with BD can be overcome by treatment with vitamin E. Lymphocytes of BD have normal sensitivity to the mutagenic agent MMC.

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Abbreviations

BD:

Behcet’s disease

MMC:

Mitomycin C

SCE:

Sister chromatid exchange

References

  • Abbas AM, Sakr HF (2013) Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet. J Physiol Biochem 69:737–750

    Article  CAS  Google Scholar 

  • Agarwal MK, Iqbal M, Athar M (2005) Vitamin E inhibits hepatic oxidative stress, toxicity and hyperproliferation in rats treated with the renal carcinogen ferric nitrilotriacetate. Redox Rep 10:62–70

    Article  CAS  Google Scholar 

  • Agrawal A, Sharma B (2010) Pesticides induced oxidative stress in mammalian systems: a review. Int J Biol Med Res 1:90–104

    Google Scholar 

  • Al-Sweedan SA, Khabour O, Isam R (2012) Genotoxicity assessment in patients with thalassemia minor. Mutat Res 744:167–171

    Article  CAS  Google Scholar 

  • Altindag O, Karakoc M, Kocyigit A, Celik H, Soran N (2007) Increased DNA damage and oxidative stress in patients with rheumatoid arthritis. Clin Biochem 40:167–171

    Article  CAS  Google Scholar 

  • Alzoubi K, Khabour O, Hussain N, Al-Azzam S, Mhaidat N (2012a) Evaluation of vitamin B12 effects on DNA damage induced by pioglitazone. Mutat Res 748:48–51

    Article  CAS  Google Scholar 

  • Alzoubi KH, Khabour OF, Rashid BA, Damaj IM, Salah HA (2012b) The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment: the role of oxidative stress. Behav Brain Res 226:205–210

    Article  CAS  Google Scholar 

  • Aslan M, Nazligu Y, Bolukbas C, Bolukbas FF, Horoz M, Dulger AC, Erdur FM, Celik H, Kocyigit A (2011) Peripheral lymphocyte DNA damage and oxidative stress in patients with ulcerative colitis. Pol Arch Med Wewn 121:223–229

    CAS  Google Scholar 

  • Ayed-Boussema I, Pascussi JM, Maurel P, Bacha H, Hassen W (2011) Zearalenone activates pregnane X receptor, constitutive androstane receptor and aryl hydrocarbon receptor and corresponding phase I target genes mRNA in primary cultures of human hepatocytes. Environ Toxicol Pharmacol 31:79–87

    Article  CAS  Google Scholar 

  • Azab M, Khabour OF, Al-Omari L, Alzubi MA, Alzoubi K (2009) Effect of every-other-day fasting on spontaneous chromosomal damage in rat’s bone-marrow cells. J Toxicol Environ Health A 72:295–300

    Article  CAS  Google Scholar 

  • Bashir S, Harris G, Denman MA, Blake DR, Winyard PG (1993) Oxidative DNA damage and cellular sensitivity to oxidative stress in human autoimmune diseases. Ann Rheum Dis 52:659–666

    Article  CAS  Google Scholar 

  • Bhatti FU, Mehmood A, Wajid N, Rauf M, Khan SN, Riazuddin S (2013) Vitamin E protects chondrocytes against hydrogen peroxide-induced oxidative stress in vitro. Inflamm Res 62:781–789

    Article  CAS  Google Scholar 

  • Evereklioglu C (2005) Current concepts in the etiology and treatment of Behcet disease. Surv Ophthalmol 50:297–350

    Article  Google Scholar 

  • Fantappie O, Lodovici M, Fabrizio P, Marchettia S, Fabbroni V, Solazzo M, Lasagna N, Pantaleo P, Mazzanti R (2004) Vitamin E protects DNA from oxidative damage in human hepatocellular carcinoma cell lines. Free Radic Res 38:751–759

    Article  CAS  Google Scholar 

  • Gulbahar O, Adisen H, Koca C, Aricioglu A, Gulekon A (2007) Changes in serum carbonyl and malondialdehyde levels following colchicine and vitamin E treatment in Behcet’s disease. Methods Find Exp Clin Pharmacol 29:521–524

    CAS  Google Scholar 

  • Hamurcu Z, Donmez-Altuntas H, Borlu M, Demirtas H, Ascioslu O (2005) Micronucleus frequency in the oral mucosa and lymphocytes of patients with Behcet’s disease. Clin Exp Dermatol 30:565–569

    Article  CAS  Google Scholar 

  • Harzallah O, Kerkeni A, Baati T, Mahjoub S (2008) Oxidative stress: correlation with Behcet’s disease duration, activity and severity. Eur J Intern Med 19:541–547

    Article  CAS  Google Scholar 

  • Hatemi G, Yazici Y, Yazici H (2013) Behcet’s syndrome. Rheum Dis Clin N Am 39:245–261

    Article  Google Scholar 

  • Huang Z, Senoh Y, Katoh S, Miwa N (2004) Preventive effects of a water-soluble derivative of chroman moiety of vitamin E on lipid hydroperoxide-induced cell injuries and DNA cleavages through repressions of oxidative stress in the cytoplasm of human keratinocytes. J Cell Biochem 92:425–435

    Article  CAS  Google Scholar 

  • Hyman M, Pizzorno J, Weil A (2005) A rational approach to antioxidant therapy and vitamin E. Altern Ther Health Med 11:14–17

    Google Scholar 

  • Ikbal M, Atasoy M, Pirim I, Aliagaoglu C, Karatay S, Erdem T (2006) The alteration of sister chromatid exchange frequencies in Behcet’s disease with and without HLA-B51. J Eur Acad Dermatol Venereol 20:149–152

    Article  CAS  Google Scholar 

  • Isik A, Koca SS, Ustundag B, Selek S (2007) Decreased total antioxidant response and increased oxidative stress in Behcet’s disease. Tohoku J Exp Med 212:133–141

    Article  Google Scholar 

  • Kan Y, Cengiz EI, Ugurlu P, Yanar M (2012) The protective role of vitamin E on gill and liver tissue histopathology and micronucleus frequencies in peripheral erythrocytes of Oreochromis niloticus exposed to deltamethrin. Environ Toxicol Pharmacol 34:170–179

    Article  CAS  Google Scholar 

  • Kao-Shan CS, Fine RL, Whang-Peng J, Lee EC, Chabner BA (1987) Increased fragile sites and sister chromatid exchanges in bone marrow and peripheral blood of young cigarette smokers. Cancer Res 47:6278–6282

    CAS  Google Scholar 

  • Karaman A, Kadi M, Kara F (2009) Sister chromatid exchange and micronucleus studies in patients with Behcet’s disease. J Cutan Pathol 36:831–837

    Article  Google Scholar 

  • Kaya Y, Cebi A, Soylemez N, Demir H, Alp HH, Bakan E (2012) Correlations between oxidative DNA damage, oxidative stress and coenzyme Q10 in patients with coronary artery disease. Int J Med Sci 9:621–626

    Article  CAS  Google Scholar 

  • Khabour OF, Alsatari ES, Azab M, Alzoubi KH, Sadiq MF (2011) Assessment of genotoxicity of waterpipe and cigarette smoking in lymphocytes using the sister-chromatid exchange assay: a comparative study. Environ Mol Mutagen 52:224–228

    Article  CAS  Google Scholar 

  • Khabour OF, Saleh N, Alzoubi KH, Hisaindee S, Al-Fyad D, Al-Kaabi L, Dodeen A, Esmadi FT (2013a) Genotoxicity of structurally related copper and zinc containing Schiff base complexes. Drug Chem Toxicol 36:435–442

    Article  CAS  Google Scholar 

  • Khabour OF, Soudah OA, Aaysh MH (2013b) Genotoxicity assessment in iron deficiency anemia patients using sister chromatid exchanges and chromosomal aberrations assays. Mutat Res 750:72–76

    Article  CAS  Google Scholar 

  • Khairallah M, Accorinti M, Muccioli C, Kahloun R, Kempen JH (2012) Epidemiology of Behcet disease. Ocul Immunol Inflamm 20:324–335

    Article  CAS  Google Scholar 

  • Kocyigit A, Keles H, Selek S, Guzel S, Celik H, Erel O (2005) Increased DNA damage and oxidative stress in patients with cutaneous leishmaniasis. Mutat Res 585:71–78

    Article  CAS  Google Scholar 

  • Maluf SW, Marroni NP, Heuser VD, Pra D (2013) DNA damage and oxidative stress in human disease. Biomed Res Int 2013:696104

    Article  Google Scholar 

  • Mateuca RA, Decordier I, Kirsch-Volders M (2012) Cytogenetic methods in human biomonitoring: principles and uses. Methods Mol Biol 817:305–334

    Article  CAS  Google Scholar 

  • M’Bemba-Meka P, Lemieux N, Chakrabarti SK (2007) Role of oxidative stress and intracellular calcium in nickel carbonate hydroxide-induced sister-chromatid exchange, and alterations in replication index and mitotic index in cultured human peripheral blood lymphocytes. Arch Toxicol 81:89–99

    Article  Google Scholar 

  • Ohta Y, Yashiro K, Ohashi K, Imai Y, Kusumoto C, Matsura T, Hidaka M, Fukuzawa K (2013) Vitamin E depletion enhances liver oxidative damage in rats with water-immersion restraint stress. J Nutr Sci Vitaminol (Tokyo) 59:79–86

    Article  CAS  Google Scholar 

  • Oztas S, Gullulu G, Tatar A, Astam N, Akyol I, Karakuzu A, Aktas A, Odabas AR (2006) Chromosome and sister chromatid exchange studies in Behcet’s patients. J Dermatol 33:406–410

    Article  Google Scholar 

  • Pacal L, Varvarovska J, Rusavy Z, Lacigova S, Stetina R, Racek J, Pomahacova R, Tanhauserova V, Kankova K (2011) Parameters of oxidative stress, DNA damage and DNA repair in type 1 and type 2 diabetes mellitus. Arch Physiol Biochem 117:222–230

    Article  CAS  Google Scholar 

  • Pal S, Polyak SJ, Bano N, Qiu WC, Carithers RL, Shuhart M, Gretch DR, Das A (2010) Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA repair enzyme NEIL1. J Gastroenterol Hepatol 25:627–634

    Article  CAS  Google Scholar 

  • Prasad K, McNair ED, Qureshi AM, Casper-Bell G (2012) Vitamin E slows the progression of hypercholesterolemia-induced oxidative stress in heart, liver and kidney. Mol Cell Biochem 368:181–187

    Article  CAS  Google Scholar 

  • Sadiq MF, Khabour OF, el-Shanti HE, Samawi HM (2000) The effect of trifluoperazine on the genotoxicity of bleomycin in cultured human lymphocytes. Drug Chem Toxicol 23:361–369

    Article  CAS  Google Scholar 

  • Saxena R, Garg P, Jain DK (2011) In vitro anti-oxidant effect of vitamin E on oxidative stress induced due to pesticides in rat erythrocytes. Toxicol Int 18:73–76

    Article  Google Scholar 

  • Sezer ED, Aksu K, Caglayan O, Keser G, Karabulut G, Ercan G (2012) DNA damage and its relationship with other oxidative stress parameters in Behcet’s disease. Rheumatol Int 32:217–222

    Article  CAS  Google Scholar 

  • Sharma RK, Sharma B (2012) In-vitro carbofuran induced genotoxicity in human lymphocytes and its mitigation by vitamins C and E. Dis Markers 32:153–163

    Article  CAS  Google Scholar 

  • Sharma RK, Rai DK, Sharma B (2012) In-vitro carbofuran induced micronucleus formation in human blood lymphocytes. Cell Mol Biol (Noisy-le-grand) 58:128–133

    CAS  Google Scholar 

  • Sonmez S, Kaya M, Aktas A, Ikbal M, Senel K (1998) High frequency of sister chromatid exchanges in lymphocytes of the patients with Behcet’s disease. Mutat Res 397:235–238

    Article  CAS  Google Scholar 

  • Sun J, Zhong W, Gu Y, Groome LJ, Wang Y (2013) 1,25(OH)D suppresses COX-2 up-regulation and thromboxane production in placental trophoblast cells in response to hypoxic stimulation. Placenta 35:143–145

  • Tang XL, Liu XJ, Sun WM, Zhao J, Zheng RL (2005) Oxidative stress in Graves’ disease patients and antioxidant protection against lymphocytes DNA damage in vitro. Pharmazie 60:696–700

    CAS  Google Scholar 

  • Taysi S, Demircan B, Akdeniz N, Atasoy M, Sari RA (2007) Oxidant/antioxidant status in men with Behcet’s disease. Clin Rheumatol 26:418–422

    Article  Google Scholar 

  • Verity DH, Wallace GR, Vaughan RW, Stanford MR (2003) Behcet’s disease: from Hippocrates to the third millennium. Br J Ophthalmol 87:1175–1183

    Article  CAS  Google Scholar 

  • Wang J, Sun P, Bao Y, Dou B, Song D, Li Y (2012) Vitamin E renders protection to PC12 cells against oxidative damage and apoptosis induced by single-walled carbon nanotubes. Toxicol In Vitro 26:32–41

    Article  Google Scholar 

  • Zana M, Szecsenyi A, Czibula A, Bjelik A, Juhasz A, Rimanoczy A, Szabo K, Vetro A, Szucs P, Varkonyi A, Pakaski M, Boda K, Rasko I, Janka Z, Kalman J (2006) Age-dependent oxidative stress-induced DNA damage in Down’s lymphocytes. Biochem Biophys Res Commun 345:726–733

    Article  CAS  Google Scholar 

  • Zingg JM, Azzi A (2004) Non-antioxidant activities of vitamin E. Curr Med Chem 11:1113–1133

    Article  CAS  Google Scholar 

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Acknowledgments

This work has been done with funds from the Research Deanship at Jordan University of Science and Technology, Grant Number (JUST-171) to OK.

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The authors have no conflict of interest to declare.

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Correspondence to Omar F. Khabour.

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Khabour, O.F., Alawneh, K., Al-Kofahi, E. et al. Assessment of genotoxicity associated with Behcet’s disease using sister-chromatid exchange assay: vitamin E versus mitomycin C. Cytotechnology 67, 1051–1057 (2015). https://doi.org/10.1007/s10616-014-9744-x

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