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Circulating Cell-Free DNA

An Up-Coming Molecular Marker in Exercise Physiology

Sports Medicine volume 42, pages 565–586 (2012)Cite this article

Abstract

The phenomenon of circulating cell-free DNA (cfDNA) concentrations is of importance for many biomedical disciplines including the field of exercise physiology. Increases of cfDNA due to exercise are described to be a potential hallmark for the overtraining syndrome and might be related to, or trigger adaptations of, immune function induced by strenuous exercise. At the same time, exercise provides a practicable model for studying the phenomenon of cfDNA that is described to be of pathophysiological relevance for different topics in clinical medicine like autoimmune diseases and cancer.

In this review, we are summarizing the current knowledge of exercise-based acute and chronic alterations in cfDNA levels and their physiological significance. The effects of acute exercise on cfDNA concentrations have been investigated in resistance exercises and in continuous, stepwise and interval endurance exercises of different durations. cfDNA concentrations peaked immediately after acute exercise and showed a rapid return to baseline levels. Typical markers of skeletal muscle damage (creatine kinase, uric acid, C-reactive protein) show delayed kinetics compared with the cfDNA peak response. Exercise parameters such as intensity, duration or average energy expenditure do not explain the extent of increasing cfDNA concentrations after strenuous exercise. This could be due to complex processes inside the human organism during and after physical activity. Therefore, we hypothesize composite effects of different physiological stress parameters that come along with exercise to be responsible for increasing cfDNA concentrations. We suggest that due to acute stress, cfDNA levels increase rapidly by a spontaneous active or passive release mechanism that is not yet known. As a result of the rapid and parallel increase of cfDNA and lactate in an incremental treadmill test leading to exhaustion within 15–20 minutes, it is unlikely that cfDNA is released into the plasma by typical necrosis or apoptosis of cells in acute exercise settings. Recently, rapid DNA release mechanisms of activated immune-competent cells like NETosis (pathogen-induced cell death including the release of neutrophil extracellular traps [NETs]) have been discovered. cfDNA accumulations might comprise a similar kind of cell death including trap formation or an active release of cfDNA. Just like chronic diseases, chronic high-intensity resistance training protocols induced persistent increases of cfDNA levels. Chronic, strenuous exercise protocols, either long-duration endurance exercise or regular high-intensity workouts, induce chronic inflammation that might lead to a slow, constant release of DNA. This could be due to mechanisms of cell death like apoptosis or necrosis. Yet, it has neither been implicated nor proven sufficiently whether cfDNA can serve as a marker for overtraining. The relevance of cfDNA with regard to overtraining status, performance level, and the degree of physical exhaustion still remains unclear. Longitudinal studies are required that take into account standardized and controlled exercise, serial blood sampling, and large and homogeneous cohorts of different athletic achievement. Furthermore, it is important to establish standardized laboratory procedures for the measurement of genomic cfDNA concentrations by quantitative real-time polymerase chain reaction (PCR). We introduce a new hypothesis based on acute exercise and chronic exposure to stress, and rapid active and passive chronic release of cfDNA fragments into the circulation.

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cfDNA
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cfDNA

References

  1. Stroun M, Anker P, Lyautey J, et al. Isolation and characterization of DNA from the plasma of cancer patients. Eur J Cancer Clin Oncol 1987 Jun; 23 (6): 707–12

    PubMed  CAS  Article  Google Scholar 

  2. Bennett RM, Gabor GT, Merritt MM. DNA binding to human leukocytes: evidence for a receptor-mediated association, internalization, and degradation of DNA. J Clin Invest 1985 Dec; 76 (6): 2182–90

    PubMed  CAS  Article  Google Scholar 

  3. Tamkovich SN, Cherepanova AV, Kolesnikova EV, et al. Circulating DNA and DNase activity in human blood. Ann N Y Acad Sci 2006 Sep; 1075: 191–6

    PubMed  CAS  Article  Google Scholar 

  4. Anker P, Stroun M, Maurice PA. Spontaneous release of DNA by human blood lymphocytes as shown in an in vitro system. Cancer Res 1975 Sep; 35 (9): 2375–82

    PubMed  CAS  Google Scholar 

  5. Gahan PB. Circulating DNA: intracellular and intraorgan messenger? Ann N Y Acad Sci 2006 Sep; 1075: 21–33

    PubMed  CAS  Article  Google Scholar 

  6. Stroun M, Lyautey J, Lederrey C, et al. About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. Clin Chim Acta 2001 Nov; 313 (1–2): 139–42

    PubMed  CAS  Article  Google Scholar 

  7. Jahr S, Hentze H, Englisch S, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 2001 Feb 15; 61 (4): 1659–65

    PubMed  CAS  Google Scholar 

  8. Suzuki N, Kamataki A, Yamaki J, et al. Characterization of circulating DNA in healthy human plasma. Clinica Chimica Acta 2008; 387: 55–8

    CAS  Article  Google Scholar 

  9. Chan KCA, Zhang J, Hui ABY, et al. Size distributions of maternal and fetal DNA in maternal plasma. Clin Chem 2004 Jan; 50 (1): 88–92

    PubMed  CAS  Article  Google Scholar 

  10. Ziegler A, Zangemeister-Wittke U, Stahel RA. Circulating DNA: a new diagnostic gold mine? Cancer Treatment Reviews 2002 Oct; 28 (5): 255–71

    PubMed  CAS  Article  Google Scholar 

  11. Van der Vaart M, Pretorius PJ. Circulating DNA: its origin and fluctuation. Ann N Y Acad Sci 2008 Aug; 1137: 18–26

    PubMed  Article  Google Scholar 

  12. Fehrenbach E, Niess AM, Schlotz E, et al. Transcriptional and translational regulation of heat shock proteins in leukocytes of endurance runners. J Appl Physiol 2000 Aug; 89 (2): 704–10

    PubMed  CAS  Google Scholar 

  13. Brancaccio P, Lippi G, Maffulli N. Biochemical markers of muscular damage. Clin Chem Lab Med 2010 Jun; 48 (6): 757–67

    PubMed  CAS  Article  Google Scholar 

  14. Chevion S, Moran DS, Heled Y, et al. Plasma antioxidant status and cell injury after severe physical exercise. Proc Natl Acad Sci U S A 2003 Apr 29; 100 (9): 5119–23

    PubMed  CAS  Article  Google Scholar 

  15. Chan KCA, Lo YMD. Circulating nucleic acids as a tumor marker. Histol Histopathol 2002; 17 (3): 937–43

    PubMed  CAS  Google Scholar 

  16. Melnikov AA, Scholtens D, Talamonti MS, et al. Methylation profile of circulating plasma DNA in patients with pancreatic cancer. J Surg Oncol 2009 Feb 1; 99 (2): 119–22

    PubMed  Article  Google Scholar 

  17. deVos T, Tetzner R, Model F, et al. Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem 2009 Jul; 55 (7): 1337–46

    PubMed  CAS  Article  Google Scholar 

  18. Gleeson M. Immune function in sport and exercise. J Appl Physiol 2007 Aug; 103 (2): 693–9

    PubMed  CAS  Article  Google Scholar 

  19. Fehrenbach E, Schneider ME. Trauma-induced systemic inflammatory response versus exercise-induced immunomodulatory effects. Sports Med 2006; 36 (5): 373–84

    PubMed  Article  Google Scholar 

  20. Northoff H, Berg A, Weinstock C. Similarities and differences of the immune response to exercise and trauma: the IFN-gamma concept. Can J Physiol Pharmacol 1998 May; 76 (5): 497–504

    PubMed  CAS  Article  Google Scholar 

  21. Atamaniuk J, Vidotto C, Tschan H, et al. Increased concentrations of cell-free plasma DNA after exhaustive exercise. Clin Chem 2004 Sep; 50 (9): 1668–70

    PubMed  CAS  Article  Google Scholar 

  22. Fatouros IG, Destouni A, Margonis K, et al. Cell-free plasma DNA as a novel marker of aseptic inflammation severity related to exercise overtraining. Clin Chem 2006 Sep; 52 (9): 1820–4

    PubMed  CAS  Article  Google Scholar 

  23. Atamaniuk J, Stuhlmeier KM, Vidotto C, et al. Effects of ultra-marathon on circulating DNA and mRNA expression of pro- and anti-apoptotic genes in mononuclear cells. Eur J Appl Physiol 2008 Nov; 104 (4): 711–7

    PubMed  CAS  Article  Google Scholar 

  24. Atamaniuk J, Vidotto C, Kinzlbauer M, et al. Cell-free plasma DNA and purine nucleotide degradation markers following weightlifting exercise. Eur J Physiol 2010 Nov; 110 (4): 695–701

    CAS  Article  Google Scholar 

  25. Fatouros IG, Jamurtas AZ, Nickolaidis MG, et al. Time sampling is crucial for measurements of cell-free plasma DNA following acute aseptic inflammation induced by exercise. Clin Biochem 2010 Nov; 43 (16–17): 1368–70

    PubMed  CAS  Article  Google Scholar 

  26. Beiter T, Fragasso A, Hudemann J, et al. Short-term treadmill running as a model for studying cell-free DNA kinetics in vivo. Clin Chem 2011 Apr; 57 (4): 633–6

    PubMed  CAS  Article  Google Scholar 

  27. Fleischhacker M, Schmidt B, Weickmann S, et al. Methods for isolation of cell-free plasma DNA strongly affect DNA yield. Clin Chim Acta 2011 Nov 20; 412 (23–24): 2085–8

    PubMed  CAS  Article  Google Scholar 

  28. Horlitz M, Lucas A, Sprenger-Haussels M. Optimized quantification of fragmented, free circulating DNA in human blood plasma using a calibrated duplex real-time PCR. PLoS One 2009 Sep 28; 4 (9): e7207

    PubMed  Article  Google Scholar 

  29. Kiode K, Sekizawa A, Iwasaki M, et al. Fragmentation of cell-free fetal DNA in plasma and urine of pregnant women. Prenat Diagn 2005 Jul; 25 (7): 604–7

    Article  Google Scholar 

  30. Sikora A, Zimmermann BG, Rusterholz C, et al. Detection of increased amounts of cell-free fetal DNA with short PCR amplicons. Clin Chem 2010 Jan; 56 (1): 136–8

    PubMed  CAS  Article  Google Scholar 

  31. Fehrenbach E, Northoff H. Free radicals, exercise, apoptosis, and heat shock proteins. Exerc Immunol Rev 2001; 7: 66–89

    PubMed  CAS  Google Scholar 

  32. Hellsten Y, Hansson HA, Johnson L, et al. Increased expression of xanthine oxidase and insulin-like growth factor I (IGF-I) immunoreactivity in skeletal muscle after strenuous exercise in humans. Acta Physiol Scand 1996 Jun; 157 (2): 191–7

    PubMed  CAS  Article  Google Scholar 

  33. Hellsten Y, Frandsen U, Orthenblad N, et al. Xanthine oxidase in human skeletal muscle following eccentric exercise: a role in inflammation. J Physiol 1997 Jan 1; 498: 239–48

    PubMed  CAS  Google Scholar 

  34. Lo YMD, Zhang J, Leung TN, et al. Rapid clearance of fetal DNA from maternal plasma. Am J Hum Genet 1999 Jan; 64 (1): 218–24

    PubMed  CAS  Article  Google Scholar 

  35. Castiglioni A, Canti V, Rovere-Querini P, et al. Highmobility group box 1 (HMGB1) as a master regulator of innate immunity. Cell Tissue Res 2011; 343: 189–99

    PubMed  CAS  Article  Google Scholar 

  36. Hashimoto T, Hussien R, Oommen S, et al. Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis. FASEB J 2007 Aug; 21 (10): 2602–12

    PubMed  CAS  Article  Google Scholar 

  37. Margonis K, Fatouros IG, Jamutas AZ, et al. Oxidative stress biomarkers response to physical overtraining: implications for diagnosis. Free Radic Biol Med 2007 Sep 15; 43 (6): 901–10

    PubMed  CAS  Article  Google Scholar 

  38. Hirose L, Nosaka K, Newton M, et al. Changes in inflammatory mediators following eccentric exercise of the elbow flexors. Exerc Immunol Rev 2004; 10: 75–90

    PubMed  Google Scholar 

  39. Coyle EF. Physical activity as a metabolic stressor. Am J Clin Nutr 2000 Aug; 72 (2 Suppl.): 512S–20S

    PubMed  CAS  Google Scholar 

  40. Neubauer O, Reichhold S, Nersesyan A, et al. Exercise-induced DNA damage: is there a relationship with inflammatory responses? Exerc Immunol Rev 2008; 14: 51–72

    PubMed  Google Scholar 

  41. Lippi G, Schena F, Salvagno GL, et al. Acute variation of biochemical markers of muscle damage following 21-km, half-marathon run. Scand J Clin Lab Invest 2008; 68 (7): 667–72

    PubMed  CAS  Article  Google Scholar 

  42. Kanter MM, Lesmes GR, Kaminsky LA, et al. Serum creatine kinase and lactate dehydrogenase changes following an eighty kilometer race: relationship to lipid peroxidation. Eur J Appl Physiol Occup Physiol 1988; 57 (1): 60–3

    PubMed  CAS  Article  Google Scholar 

  43. Ratamess NA, Falvo MJ, Mangine GT, et al. The effect of rest interval length on metabolic responses to the bench press exercise. Eur J Appl Physiol 2007 May; 100 (1): 1–17

    PubMed  Article  Google Scholar 

  44. Lehmann M, Berg A, Kapp R, et al. Correlations between laboratory testing and distance running performance in marathoners of similar performance ability. Int J Sports Med 1983 Nov; 4 (4): 226–30

    PubMed  CAS  Article  Google Scholar 

  45. Niess AM, Fehrenbach E, Strobel G, et al. Evaluation of stress response to interval training at low and moderate altitude. Med Sci Sports Exerc 2003 Feb; 35 (2): 263–9

    PubMed  Article  Google Scholar 

  46. Williams C, Nute ML. Some physiological demands of a half-marathon race on recreational runners. Br J Sports Med 1983 Sep; 17 (3): 152–61

    PubMed  CAS  Article  Google Scholar 

  47. Zaccaria M, Ermolao A, Roi GS, et al. Leptin reduction after endurance races differing in duration and energy expenditure. Eur J Appl Physiol 2002 Jun; 87 (2): 108–11

    PubMed  CAS  Article  Google Scholar 

  48. Fehrenbach E, Passek F, Niess AM, et al. HSP expression in human leukocytes is modulated by endurance exercise. Med Sci Sports Exerc 2000 Mar; 32 (3): 592–600

    PubMed  CAS  Article  Google Scholar 

  49. Kim HJ, Lee YH, Kim CK. Biomarkers of muscle and cartilage damage and inflammation during 200 km run. Eur J Appl Physiol 2007 Mar; 99 (4): 443–7

    PubMed  CAS  Article  Google Scholar 

  50. Kraemer WJ, Volek JS, Bush JA, et al. Hormonal responses to consecutive days of heavy-resistance exercise with or without nutritional supplementation. J Appl Physiol 1998 Oct; 85(4): 1544–55

    PubMed  CAS  Google Scholar 

  51. Achten J, Venables MC, Jeukendrup AE. Fat oxidation rates are higher during running compared with cycling over a wide range of intensities. Metabolism 2003 Jun; 52 (6):747–52

    PubMed  CAS  Article  Google Scholar 

  52. Niess AM, Hartmann A, Grünert-Fuchs M, et al. DNA damage after exhaustive treadmill running in trained and untrained men. Int J Sports Med 1996 Aug; 17 (6): 397–403

    PubMed  CAS  Article  Google Scholar 

  53. Mastaloudis A, Morrow JD, Hopkins DW, et al. Antioxidant supplementation prevents exercise-induced lipid peroxidation, but not inflammation, in ultramarathon runners. Free Radic Biol Med 2004 May 15; 36 (10): 1329–41

    PubMed  CAS  Article  Google Scholar 

  54. Noakes TD, Carter JW. The response of plasma biochemical parameters to a 56-km race in novice and experienced ultra-marathon runners. Eur J Appl Physiol. 1982; 42: 179–86

    Article  Google Scholar 

  55. Paul GL, DeLany JP, Snook JT, et al. Serum and urinary markers of skeletal muscle tissue damage after weight lifting exercise. Eur J Appl Physiol Occup Physiol 1989; 58 (7): 786–90

    PubMed  CAS  Article  Google Scholar 

  56. Adams WC, Fox RH, Fry AJ, et al. Thermoregulation during marathon running in cool, moderate, and hot environments. J Appl Physiol 1975 Jun; 38 (6): 1030–7

    PubMed  CAS  Google Scholar 

  57. Mastaloudis A, Leonard SW, Traber MG. Oxidative stress in athletes during extreme endurance exercise. Free Radic Biol Med 2001 Oct 1; 31 (7): 911–22

    PubMed  CAS  Article  Google Scholar 

  58. Dumke CL, Shooter L, Lind RH, et al. Indirect calorimetry during ultradistance running: a case report. J Sci Sports Med 2006; 5: 692–8

    Google Scholar 

  59. Hudson MB, Hosick PA, McCaulley GO, et al. The effect of resistance exercise on humoral markers of oxidative stress. Med Sci Sports Exerc 2008 Mar; 40 (3): 542–8

    PubMed  CAS  Article  Google Scholar 

  60. Scala D, McMillan J, Blessing D, et al. Metabolic cost of a preparatory phase of training in weight lifting: a practical observation. J Appl Sports Sci Res 1987; 1: 48–52

    Google Scholar 

  61. Branth S, Hambraeus L, Piehl-Aulin K, et al., Metabolic stress-like condition can be induced by prolonged strenuous exercise in athletes. Ups J Med Sci 2009; 114(1): 12–25

    PubMed  Article  Google Scholar 

  62. Cooper CE, Vollaard NB, Choueiri T, et al. Exercise, free radicals and oxidative stress. Biochem Soc Trans 2002 Apr; 30 (2): 280–5

    PubMed  CAS  Article  Google Scholar 

  63. Niess AM, Sommer M, Schlotz E, et al. Expression of the inducible nitric oxide synthase (iNOS) in human leukocytes: responses to running exercise. Med Sci Sports Exerc 2000 Jul; 32 (7): 1220–5

    PubMed  CAS  Article  Google Scholar 

  64. Bianchi DW. Circulating fetal DNA: its origin and diagnostic potential: a review. Placenta 2004 Apr; 25 Suppl. A: 93–101

    Article  Google Scholar 

  65. Mooren FC, Blöming D, Lechtermann A, et al. Lymphocyte apoptosis after exhaustive and moderate exercise. J Appl Physiol 2002 Jul; 93 (1): 147–53

    PubMed  CAS  Google Scholar 

  66. Goldstein JC, Kluck RM, Green DR. A single cell analysis of apoptosis: ordering the apoptotic phenotype. Ann N Y Acad Sci 2000; 926: 132–41

    PubMed  CAS  Article  Google Scholar 

  67. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972 Aug; 26 (4): 239–57

    PubMed  CAS  Article  Google Scholar 

  68. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol 1980; 68: 251–306

    PubMed  CAS  Article  Google Scholar 

  69. Goldstein JC, Waterhouse NJ, Juin P, et al. The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant. Nat Cell Biol 2000 Mar; 2 (3): 156–62

    PubMed  CAS  Article  Google Scholar 

  70. Mars M, Govender S, Weston A, et al. High intensity exercise: a cause of lymphocyte apoptosis? Biochem Biophys Res Commun 1998 Aug 19; 249 (2): 366–70

    PubMed  CAS  Article  Google Scholar 

  71. Krüger K, Agnischock S, Lechtermann A, et al. Intensive resistance exercise induces lymphocyte apoptosis via cortisol and glucocorticoid receptor-dependent pathways. J Appl Physiol 2011 May; 110(5): 1226–32

    PubMed  Article  Google Scholar 

  72. Brinkmann V, Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol 2007 Aug; 5 (8): 577–82

    PubMed  CAS  Article  Google Scholar 

  73. Hawley CJ, Schoene RB. Overtraining syndrome: a guide to diagnosis, treatment, and prevention. Phys Sportsmed 2003 Jun; 31 (6): 25–31

    PubMed  Google Scholar 

  74. Rietjens GJWM, Kuipers H, Adam JJ, et al. Physiological, biochemical and psychological markers of strenuous training-induced fatigue. Int J Sports Med 2005 Jan–Feb; 26 (1): 16–26

    PubMed  CAS  Article  Google Scholar 

  75. Swanson DR. Atrial fibrillation in athletes: implicit literature-based connections suggest that overtraining and subsequent inflammation may be a contributory mechanism. Med Hypotheses 2006; 66 (6): 1085–92

    PubMed  Article  Google Scholar 

  76. Meeusen R, Watson P, Hasegawa H, et al. Brain neurotransmitters in fatigue and overtraining. Appl Physiol Nutr Metab 2007 Oct; 32 (5): 857–64

    PubMed  CAS  Article  Google Scholar 

  77. Urhausen A, Kindermann W. Diagnosis of overtraining: what tools do we have? Sports Med 2002; 32 (2): 95–102

    PubMed  Article  Google Scholar 

  78. Urhausen A, Gabriel H, Kindermann W. Blood hormones as markers of training stress and overtraining. Sports Med 1995 Oct; 20 (4): 251–76

    PubMed  CAS  Article  Google Scholar 

  79. Milne GL, Musiek ES, Morrow JD. F2-isoprostanes as markers of oxidative stress in vivo: an overview. Bio-markers 2005 Nov; 10 Suppl. 1: 10–23

    Google Scholar 

  80. Halson SL, Jeukendrup AE. Does overtraining exist? An analysis of overreaching and overtraining research. Sports Med 2004; 34 (14): 967–81

    PubMed  Article  Google Scholar 

  81. Mackinnon LT. Overtraining effects on immunity and performance in athletes. Immun Cell Bio 2000; 78: 502–9

    CAS  Article  Google Scholar 

  82. Stroun M, Maurice P, Vasioukhin V, et al. The origin and mechanism of circulating DNA. Ann N Y Acad Sci 2000 Apr; 906: 161–8

    PubMed  CAS  Article  Google Scholar 

  83. Pedersen BK, Steensberg A. Exercise and hypoxia: effects on leukocytes and interleukin-6-shared mechanisms? Med Sci Sports Exerc 2002 Dec; 34 (12): 2004–13

    PubMed  CAS  Article  Google Scholar 

  84. von Köckritz-Blickwede M, Nizet V. Innate immunity turned inside-out: antimicrobial defense by phagocyte extracellular traps. J Mol Med (Berl) 2009 Aug; 87 (8): 775–83

    Article  Google Scholar 

  85. Record M, Subra C, Silvente-Poirot S, et al. Exosomes as intercellular signalosomes and pharmacological effectors. Biochem Pharmacol 2011 May 15; 81 (10): 1171–82

    PubMed  CAS  Article  Google Scholar 

  86. Kocsis AK, Szabolcs A, Hofner P, et al. Plasma concentrations of high-mobility group box protein 1, soluble receptor for advanced glycation end-products and circulating DNA in patients with acute pancreatitis. Pancreatology 2009; 9 (4): 383–91

    PubMed  CAS  Article  Google Scholar 

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Acknowledgements

The authors thank the reviewer for the many constructive comments on the first version of their review and Katherine E. Curtis for proof reading the manuscript. No funding was received to assist in the preparation of this article. The authors have no conflicts of interest to declare that are directly relevant to the content of this article.

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  1. Department of Sports Medicine, Faculty of Social Science, Media and Sport, Johannes Gutenberg-University, Albert-Schweitzer-Straße 22, 55128, Mainz, Germany

    Sarah Breitbach, Suzan Tug &  Perikles Simon

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  1. Sarah Breitbach
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  2. Suzan Tug
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Correspondence to Perikles Simon.

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Breitbach, S., Tug, S. & Simon, P. Circulating Cell-Free DNA. Sports Med 42, 565–586 (2012). https://doi.org/10.2165/11631380-000000000-00000

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Keywords

  • Resistance Exercise
  • Endurance Exercise
  • Strenuous Exercise
  • Uric Acid Concentration
  • Average Energy Expenditure