Zuhal HAMURCU, Feyzullah KOCA, Neşe KOCAKULAK AKPINAR, Hamiyet DONMEZ ALTUNTAS, Gönül SUNGUR, Bekir ÇOKSEVİM

Yüksek İrtifada Yapılan Egzersizin İnsan Periferal Lenfositlerinde Kromozomal DNA Hasarına Etkisi

Yüksek irtifa hipoksi ve hipoksik egzersiz oksidatif DNA hasarına neden olabilir. Çalışmamız 1055m ve 2500m’de yapılan egzersizin mikronükleus (MN) sıklığı üzerindeki etkisi araştırıldı. MN frekansı, kromozomal hasarın, genom kararsızlığının bir biyolojik işaretidir. 10 erkek, 10 kadın toplam 20 sağlıklı denek çalışmaya dahil edildi. Her iki yerde 5 gün boyunca günde 3 saat egzersiz yaptılar. Egzersizden önce ve egzersizden hemen sonra 1055 m ve 2500 m yükseklikte periferik kan örnekleri hem birinci hem de beşinci günde kültürlendi. Hastaların mitojenle uyarılmış lenfositlerinden elde edilen çift çekirdekli hücrelerde MN değerlerinin sayısı kaydedildi. 1055m koşullarında yapılan egzersizin MN oluşumunu indüklediğini bulduk (p

Effects of Exercise Performed at High Altitude on the Chromosomal DNA Damage in Human Peripheral Lymphocytes

High altitude hypoxia and hypoxic exercise may induce oxidative DNA damage.Our study was investigated the effect on the micronucleus (MN) frequency of performed exercise at 1055m and at 2500m. MN frequency is a biomarker of chromosomal damage,genome instability. 10 female and 10 male totally 20 subject were included in the study. They performed exercise 3 hours per day during5 days at each two location. The peripheral blood samples obtained before exercise and immediately after the exercise at 1055 m and2500 m altitude both first day and fifth day were cultured. The number of MN values was scored in binucleated cells obtained frommitogen-stimulated lymphocytes of subjects. We found that exercise performed at 1055m conditions induced MN formation (p

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1. P.Moller, Genotoxicity of environmental agents assessed by the alkaline comet assay, Basic Clin Pharmacol Toxicol., 1 (2005) 1-42.
2. J.A. Jefferson, J.Simoni , E. Escudero, M.E. Hurtado , E.R. Swenson , D.E. Wesson , G.F. Schreiner ,R.B. Schoene , R.J. Johnson , A. Hurtado , Increased oxidative stres following acute and chronic high altitude exposure, High Altitude Med Biol., 5 (2004) 61-9.
3. G.W. Davison, Exercise and Oxidative Damage in Nucleoid DNA Quantified Using Single Cell Gel Electrophoresis: Present and Future Application, Front Physiol., 7 (2016) 249.
4. H. Kumar, D.K. Choi, Hypoxia Inducible Factor Pathway and Physiological Adaptation: A Cell Survival Pathway? Mediators Inflamm., (2015) 584758
5. G. Alkorta-Aranburu, C.M. Beall, D.B. Witonsky, A. Gebremedhin, J.K. Pritchard, A. Di Rienzo, The genetic architecture of adaptations to high altitude in Ethiopia, PLoS Genet., 8 (2012) 1003.
6. E.W. Askew, Work at high altitude and oxidative stress: antioxidant nutrients, Toxicol., 180 (2002) 107-119.
7. P. Møller, L. Risom, C. Lundby, L. Mikkelsen, S. Loft , Hypoxia and oxidation levels of DNA and lipids in humans and animal experimental models, IUBMB Life., 60 (2008) 707-23.
8. A. Dosek, H. Ohno, Z. Acs, A.W. Taylor, Z. Radak, High altitude and oxidative stress, Respir Physiol Neurobiol., 158 (2007) 128-131.
9. Z. Radak, K. Suzuki, M. Higuchi, L. Balogh, I. Boldogh, E. Koltai, Physical exercise, reactive oxygen species and neuroprotection, Free Radic Biol Med., 98 (2016)187-196.
10. R.J. Bloomer, A.H. Goldfarb, L. Wideman, M.J. McKenzie, L.A. Consitt, Effects of acute aerobic and anaerobic exercise on blood markers of oxidative stress, J. Strength. Cond. Res., 19 (2005) 276-85.
11. R.J. Bloomer, A.H. Goldfarb, J.M. Mckenzie, Oxidative stress response to aerobic exercise: Comparison of antioxidant supplements, Med Sci Sports Exerc., 38 (2006) 1098-105.
12. Z. Hamurcu , F. Bayram, G. Kahriman, H. Dönmez-Altuntas, G. Baskol, Micronucleus frequency in lymphocytes and 8-hydroxydeoxyguanosine level in plasma of women with polycystic ovary syndrome, Gynecol Endocrinol., 26 (2010) 590-5.
13. R.P. Araldi, T.C. de Melo, T.B. Mendes, P.L. de Sá Júnior, B.H. Nozima, E.T. Ito, R.F. de Carvalho, E.B. de Souza, R. de Cassia Stocco, Using the comet and micronucleus assays for genotoxicity studies: A review, Biomed. Pharmacother., 72 (2015) 74-82.
14. M. Kirsch-Volders, S. Bonassi, S. Knasmueller, N. Holland, C. Bolognesi, M.F. Fenech, Commentary: critical questions, misconceptions and a road map for improving the use of the lymphocyte cytokinesis-block micronucleus assay for in vivo biomonitoring of human exposure to genotoxic chemicals-a HUMN project perspective, Mutat. Res. Rev .Mutat Res., 759 (2014) 49-58.
15. M. Fenech, The micronucleus assay determination of chromosomal level DNA damage, Method. Mol. Biol., 410 (2008) 185-216.
16. M. Fenech, M. Kirsch-Volders, A.T. Natarajan, J. Surralles, J.W. Crott, J. Parry, H. Norppa, D.A. Eastmond, J.D. Tucker, P. Thomas, Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells, Mutagenesis., 26 (2011) 125- 32.
17. A. Wozniak, G. Drewa, G. Chesy, A. Rakowski, M. Rozwodowska, D. Olszewska, Effect of altitude training on the peroxidation and antioxidant enzymes in sportsmen, Med. Sci. Sport. Exer., 33 (2001) 1109-13.
18. P. Møller, S. Loft , C. Lundby, N.V. Olsen, Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans, FASEB J., 15 (2001) 1181-6.
19. V. Pialoux, R. Mounier, E. Rock, A. Mazur, L. Schmitt, J.P. Richalet, P. Robach, J. Brugniaux, J. Coudert , N. Fellmann, Effects of the ‘live high-train low’ method on prooxidant/ antioxidant balance on elite athletes, Eur. J. Clin. Nutr., 63 (2009) 756-762.
20. S. Sinha, A. Dutta, S.A. Singh, U.S. Ray, Protein nitration, lipid peroxidation and DNA damage at high altitude in acclimatized lowlanders and native highlanders: relation with oxygen consumption, Respir. Physiol. Neurobiol., 171 (2010) 115-21.
21. T.J. Vasankari, U.M. Kujala, H. Rusko, S. Sarna, M. Ahotupa, The effect of endurance exercise at moderate altitude on serum lipid peroxidation and antioxidative functions in humans, Eur. J. Appl. Physiol., 75 (1997) 396-399.
22. W. H. Chao, E.W. Askew, D.E. Roberts, S.M. Wood, J.B. Perkins, Oxidative stress in humans during work at moderate altitude, J. Nutr., 129 (1999) 2009-11.
23. J.M. Pfeiffer, E.W.Askew, D.E. Roberts, S.M. Wood, J.E. Benson, S.C. Johnson, M.S. Freedman, Effect of antioxidant supplementation on urine and blood markers of oxidative stress during extended moderate-altitude training, Wilderness Environ. Med., 10(1999) 66-74.
24. J. Magalhães, A. Ascensão, G. Viscor, J. Soares, J. Oliveira, F. Marques, J. Duarte, Oxidative stress in humans during and after 4 hours of hypoxia at a simulated altitude of 5500 m, Aviat. Space. Environ. Med., 75 (2004)16-22.
25. Z. Hamurcu, H. Dönmez-Altuntas, T. Patiroglu, Basal level micronucleus frequency in stimulated lymphocytes of untreated patients with leukemia, Cancer Genet. Cytogenet., 180 (2008) 140-4.
26. M.Fenech, Cytokinesis-block micronucleus cytome assay, Nat. Protoc., 2 (2007) 1084-104.
27. B. Tomasello, S. Grasso, G. Malfa, S. Stella, M. Favetta, M. Renis, Double-face activity of resveratrol in voluntary runners: assessment of DNA damage by comet assay, J. Med. Food., 15 (2012) 441-447.
28. K.H. Wagner, S. Reichhold, O. Neubauer, Impact of endurance and ultra endurance exercise on DNA damage, Ann. NY Acad. Sci., 1229 (2011) 115-23.
29. M.C. Fogarty, C.M. Hughes, G. Burke, J.C. Brown, T.R.Trinick, E. Duly, D.M Bailey, G.W. Davison, Exercise-induced lipid peroxidation: Implications for deoxyribonucleic acid damage and systemic free radical generation, Environ. Mol. Mutagen., 52 (2011) 35-42.
30. G. Gandhi, G. Chopra, DNA damage in peripheral blood leukocytes of physically active individuals as measured by the alkaline single cell gel electrophoresis assay, Environ. Mol. Mutagen., 50 (2009) 291-303.
31. Z. Radak, J. Pucsuk, S. Boros, L. Josfai, A.W. Taylor, Changes in urine 8-hydroxydeoxyguanozine levels of super marathon runners during a four-day race period, Life Sci., 66 (2000) 1763-1767.
32. V. Nair-Shalliker, M. Fenech, P.M. Forder, M.S. Clements, B.K. Armstrong, Sunlight and vitamin D affect DNA damage, cell division and cell death in human lymphocytes: a crosssectional study in South Australia, Mutagen., 27 (2012) 609- 14.
33. Z. Radak, Z. Zhao, E. Koltai, H. Ohno, M. Atalay, Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling, Antioxid. Redox. Signal., 18 (2013) 1208- 46.
34. Z. Hamurcu, H. Demirtas, O. Ascioglu, H. Dönmez-Altuntas,E. Aktas, Micronucleus evaluation in mitogen-stimulated lymphocytes of PUVA treated patients, Tohoku J. Exp. Med., 198 (2002) 11-21.
35. Z. Hamurcu, N. Saritas, G. Baskol, N. Akpinar, Effect of wrestling exercise on oxidative DNA damage, nitric oxide level and paraoxonase activity in adolescent boys, Pediatr. Exerc. Sci., 22 (2010) 60-68.
36. H.E.Poulsen, A.Weimann, S. Loft, Methods to detect DNA damage by free radicals: relation to exercise, Proc. Nutr. Soc., 58 (1999) 1007-1014.
37. C. Lundby, H. Pilegaard, G.Van Hall, M. Sander, J. Calbet, S. Loft, P. Møller, Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia, Toxicol., 192 (2003) 229-36.
38. S.W.Maluf, Monitoring DNA damage following radiation exposure using cytokinesis-block micronucleus method and alkaline single-cell gel electrophoresis, Clin. Chim. Acta., 347 (2004) 15-24
39. S.K.Powers, W.B Nelson, M.B. Hudson, Exercise-induced oxidative stress in humans: cause and consequences, Free Radic. Biol. Med., 51 (2011) 942-50.
40. T. Ohkuwa, H. Itoh, T. Yamamoto, C. Minami, Y. Yamazaki, S. Kimoto, R. Yoshida, Effects of hypoxia and hypoxic training on 8-hydroxydeoxyguanosine and glutathione levels in the liver, Metabolism., 53 (2004) 716-719.
41. C. Schiffl, C. Zieres, H. Zankl, Exhaustive physical exercise increases frequency of micronuclei, Mutat. Res., 389 (1997) 243-246. 42. M.Fenech, S. Bonassi, The effect of age, gender, diet and lifestyle on DNA damage measured using micronucleus frequency in human peripheral blood lymphocytes, Mutagen., 26 (2011) 43-9.
43. A. Hartmann, S. Pfuhler, C. Dennog, D. Germadnik, A. Pilger, G. Speit , Exercise-induced DNA effects in human leukocytes are not accompanied by increased formation of 8-hydroxy2’-deoxyguanosine or induction of micronuclei, Free Radic. Biol. Med., 24 (1998) 245-251.
44. K.Umegaki, M. Higuchi, K. Inoue, T. Esashi, Influence of one bout of intensive running on lymphocyte micronucleus frequencies in endurance-trained and untrained men, Int. J. Sports Med., 19 (1998) 581-585.
45. S. Reichhold, O. Neubauer, V. Ehrlich, S. Knasmüller, K.H.Wagner, No acute and persistent DNA damage after an Ironman triathlon, Cancer Epidemiol. Biomark. Prev., 17 (2008) 1913-1919.
46. S. Meintières, A. Biola, M. Pallardy, D. Marzin, Apoptosis can be a confusing factor in in vitro clastogenic assays, Mutagen., 16 (2001) 243-50.
47. N. Holland, A. Fucic, D.F. Merlo, R. Sram, M. KirschVolders, Micronuclei in neonates and children: effects of environmental, genetic, demographic and disease variables, Mutagen., 26 (2011) 51-56.
48. M.G.Andreassi, R. Barale, P. Iozzo, E. Picano, The association of micronucleus frequency with obesity, diabetes and cardiovascular disease, Mutagen., 26 (2011) 77-83.
49. M. Fenech, The Genome Health Clinic and Genome Health Nutrigenomics concepts: diagnosis and nutritional treatment of genome and epigenome damage on an individual basis, Mutagen., 20 (2005) 255-69.
50. L.Migliore, F. Coppedè, M. Fenech, P. Thomas P, Association of micronucleus frequency with neurodegenerative diseases, Mutagen., 26 (2011) 85-92.