Skip to main content
SpringerLink
Log in

Antioxidant vitamins and cancer risk: is oxidative damage to DNA a relevant biomarker?

  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Oxidative damage to DNA is regarded as an important step in carcinogenesis. These lesions may arise as a consequence of exposure to xenobiotics, but are also generated as a consequence of endogenous generation of oxidizing compounds. Measurements of oxidative damage to guanines, such as 8-oxo-7, 8-dihydroguanine (8-oxodG) are increasingly being regarded as reliable biomarkers of oxidative stress and they may have a predictive value of cancer risk, although this needs to be established independently in several cohort studies. A survey of intervention studies of the ingestion of antioxidant-containing foods or tablets of antioxidants indicate that about one-third of the studies reported a protective effect in terms of lower levels of oxidative damage to DNA in white blood cells or decreased urinary excretion of 8-oxodG. Although firm conclusions cannot be reached, there appears to be links between ingestion of antioxidants, oxidative damage to DNA, and risk of cancer.

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

Similar content being viewed by others

References

  1. Astley SB, Lindsay DG (2002) European research on the functional effects of dietary antioxidants (EUROFEDA). Conclusions. Mol Aspects Med 23:287–291

    Article  Google Scholar 

  2. de la Asuncion JG, del Olmo ML, Sastre J, Millan A, Pellin A, Pallardo FV, Vina J (1998) AZT treatment induces molecular and ultrastructural oxidative damage to muscle mitochondria. Prevention by antioxidant vitamins. J Clin Invest 102:4–9

    Article  Google Scholar 

  3. van den Berg R, van Vliet T, Broekmans WMR, Cnubben NHP, Vaes WHJ, Roza L, Haenen GRMM, Bast A, van den Berg H (2001) A vegetable/fruit concentrate with high antioxidant capacity has no effect on biomarkers of antioxidant status in male smokers. J Nutr 131:1714–1722

    Google Scholar 

  4. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2007) Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297:842–857

    Article  CAS  Google Scholar 

  5. Boyle SP, Dobson VL, Duthie SJ, Hinselwood DC, Kyle JAM, Collins AR (2000) Bioavailability and efficiency of rutin as an antioxidant: a human supplementation study. Eur J Clin Nutr 54:774–782

    Article  CAS  Google Scholar 

  6. Cadet J, Douki T, Gasparutto D, Ravanat JL (2003) Oxidative damage to DNA: formation, measurement and biochemical features. Mutat Res 531:5–23

    CAS  Google Scholar 

  7. Cerutti PA (1994) Oxy-radicals and cancer. Lancet 344:862–863

    Article  CAS  Google Scholar 

  8. Cheng KC, Cahill DS, Kasai H, Nishimura S, Loeb LA (1992) 8-hydroxyguanine, an abundant form of oxidative DNA damage causes G → T and A → C substitutions. J Biol Chem 267:166–172

    CAS  Google Scholar 

  9. Collins AR, Cadet J, Möller L, Poulsen HE, Vina J (2004) Are we sure we know how to measure 8-oxo-7,8-dihydroguanine in DNA from human cells? Arch Biochem Biophys 423:57–65

    Article  CAS  Google Scholar 

  10. Collins AR, Harrington V, Drew J, Melvin R (2003) Nutritional modulation of DNA repair in a human intervention study. Carcinogenesis 24:511–515

    Article  CAS  Google Scholar 

  11. 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  Google Scholar 

  12. Cooke MS, Evans MD, Podmore ID, Herbert KE, Mistry N, Mistry P, Hickenbotham PT, Hussieni A, Griffiths HR, Lunec J (1998) Novel repair action of vitamin C upon in vivo oxidative DNA damage. FEBS Lett 363:363–367

    Article  Google Scholar 

  13. Cooke MS, Olinski R, Evans MD (2006) Does measurement of oxidative damage to DNA have clinical significance? Clin Chim Acta 365:30–49

    Article  CAS  Google Scholar 

  14. Dennog C, Radermacher P, Barnett YA, Speit G (1999) Antioxidant status in humans after exposure to hyperbaric oxygen. Mutat Res 428:83–89

    CAS  Google Scholar 

  15. Dizdaroglu M (1992) Oxidative damage to DNA in mammalian chromatin. Mutat Res 275:331–342

    CAS  Google Scholar 

  16. Duthie SJ, Jenkinson AM, Crozier A, Mullen W, Pirie L, Kyle J, Yap LS, Christen P, Duthie GG (2006) The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers. Eur J Nutr 45:113–122

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  18. Evans MD, Cooke MS (2004) Factors contributing to the outcome of oxidative damage to nucleic acids. BioEssays 26:533–542

    Article  CAS  Google Scholar 

  19. Evans MD, Cooke MS (eds) (2007) Oxidative damage to nucleic acids. Landes Bioscience and Springer, Georgetown

    Google Scholar 

  20. Fan W-Y, Ogusu K, Kouda K, Nakamura H, Satoh T, Ochi H, Takeuchi H (2000) Reduced oxidative DNA damage by vegetable juice intake: a controlled trial. J Physiol Anthropol 19:287–289

    Article  CAS  Google Scholar 

  21. Freese R, Dragsted LO, Loft S, Mutanen M (2007) No effect on oxidative stress biomarkers by modified intakes of polyunsaturated fatty acids or vegetables and fruit. Eur J Clin Nutr. doi:10.1038/sj.ejcn.1602865

  22. Gackowski D, Kruszewsk M, Banaszkiewicz Z, Jawien A, Olinski R (2002) Lymphocyte labile iron pool, plasma iron, transferrin saturation and ferritin levels in colon cancer patients. Acta Biochim Pol 49:269–272

    CAS  Google Scholar 

  23. Gackowski D, Kruszewski M, Bartlomiejczyk T, Jawien A, Ciecierski M, Olinski R (2002) The level of 8-oxo-7,8-dihydro-2′-deoxyguanosine is positively correlated with the size of the labile iron pool in human lymphocytes. J Biol Inorg Chem 7:548–550

    Article  CAS  Google Scholar 

  24. Gill CIR, Haldar S, Porter S, Matthews S, Sullivan S, Coulter J, McGlynn H, Rowland I (2004) The effect of cruciferous and leguminous sprouts on genotoxicity, in vitro and in vivo. Cancer Epidemiol Biomarkers Prev 13:1199–1205

    Google Scholar 

  25. 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  Google Scholar 

  26. Hakim IA, Harris RB, Brown S, Chow HH, Wiseman S, Agarwal S, Talbot W (2003) Effect of increased tea consumption on oxidative DNA damage among smokers: a randomized controlled study. J Nutr 133:3303S–3309S

    CAS  Google Scholar 

  27. Hakim IA, Harris RB, Chow HH, Dean M, Brown S, Ali IU (2004) Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers: role of glutathione S-transferase genotypes. Cancer Epidemiol Biomarkers Prev 13:242–249

    Article  CAS  Google Scholar 

  28. Halliwell B (1996) Oxidative stress, nutrition and health. Experimental strategies for optimization of nutritional antioxidant intake in humans. Free Radic Res 25:57–74

    Article  CAS  Google Scholar 

  29. Herbert KE, Fletcher S, Chauhan D, Ladapo A, Nirwan J, Munson S, Mistry P (2006) Dietary supplementation with different vitamin C doses: no effect on oxidative DNA damage in healthy people. Eur J Nutr 45:97–104

    Article  CAS  Google Scholar 

  30. Huang H-Y, Helzlsouer KJ, Appel LJ (2000) The effects of vitamin C and vitamn E on oxidative DNA damage: Results from a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 9:647–652

    CAS  Google Scholar 

  31. IARC (2003) IARC handbooks of cancer prevention. Fruit and vegetables. IARC Press, Iyon

    Google Scholar 

  32. Jackson AL, Loeb LA (2001) The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat Res 477:7–21

    CAS  Google Scholar 

  33. Jacob RA, Kelley DS, Pianalto FS, Swendseid ME, Henning SM, Zhang JZ, Ames BN, Fraga CG, Peters JH (1991) Immunocompetence and oxidant defense during ascorbate depletion of healthy men. Am J Clin Nutr 54:1302S–1309S

    CAS  Google Scholar 

  34. Jacobson JS, Begg MD, Wang LW, Wang Q, Agarwal M, Norkus E, Singh VN, Young T-L, Yang D, Santella RM (2000) Effects of a 6-month vitamin intervention on DNA damage in heavy smokers. Cancer Epidemiol Biomarkers Prev 9:1303–1311

    CAS  Google Scholar 

  35. Janse van RC, Erasmus E, Loots dT, Oosthuizen W, Jerling JC, Kruger HS, Louw R, Brits M, van der Westhuizen FH (2005) Rosa roxburghii supplementation in a controlled feeding study increases plasma antioxidant capacity and glutathione redox state. Eur J Nutr 44:452–457

    Article  Google Scholar 

  36. Jenkinson AM, Collins AR, Duthie SJ, Wahle KWJ, Duthie GG (1999) The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes. FASEB J 13:2138–2142

    CAS  Google Scholar 

  37. Kiefer I, Prock P, Lawrence C, Wise J, Bieger W, Bayer P, Rathmanner T, Kunze M, Rieder A (2004) Supplementation with mixed fruit and vegetable juice concentrates increased serum antioxidants and folate in healthy adults. J Am Coll Nutr 23:205–211

    Google Scholar 

  38. Kiokias S, Gordon MH (2003) Dietary supplementation with a natural carotenoid mixture decreases oxidative stress. Eur J Clin Nutr 57:1135–1140

    Article  CAS  Google Scholar 

  39. Klaunig JE, Xu Y, Han C, Kamendulis LM, Chen J, Heiser C, Gordon MS, Mohler III ER (1999) The effect of tea consumption on oxidative stress in smokers and nonsmokers. Proc Soc Exp Biol Med 220:249–254

    Article  CAS  Google Scholar 

  40. Lean MEJ, Noroozi M, Kelly I, Burns J, Talwar D, Sattar N, Crozier A (1999) Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 48:176–181

    Article  CAS  Google Scholar 

  41. Loft S, Vistisen K, Ewertz M, Tjønneland A, Overvad K, Poulsen HE (1992) Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index. Carcinogenesis 13:2241–2247

    Article  CAS  Google Scholar 

  42. Luo H, Tang L, Tang M, Billam M, Huang T, Yu J, Wei Z, Liang Y, Wang K, Zhang ZQ, Zhang L, Wang JS (2006) Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver cancer: modulation of urinary excretion of green tea polyphenols and 8-hydroxydeoxyguanosine. Carcinogenesis 27:262–268

    Article  CAS  Google Scholar 

  43. Machowetz A, Poulsen HE, Gruendel S, Weimann A, Fito M, Marrugat J, de la Torre R, Salonen JT, Nyyssonen K, Mursu J, Nascetti S, Gaddi A, Kiesewetter H, Baumler H, Selmi H, Kaikkonen J, Zunft HJ, Covas MI, Koebnick C (2007) Effect of olive oils on biomarkers of oxidative DNA stress in Northern and Southern Europeans. FASEB J 21:45–52

    Article  CAS  Google Scholar 

  44. Mitchell JH, Collins AR (1999) Effects of a soy milk supplementation on plasma cholesterol levels and oxidative DNA damage in men—a pilot study. Eur J Nutr 38:143–148

    Article  CAS  Google Scholar 

  45. Møller P, Loft S (2002) Oxidative DNA damage in white blood cells of humans in dietary antioxidant intervention studies. Am J Clin Nutr 76:303–310

    Google Scholar 

  46. Møller P, Loft S (2004) Interventions with antioxidants and nutrients in relation to oxidative DNA damage and repair. Mutat Res 551:79–89

    Google Scholar 

  47. Møller P, Loft S (2006) Dietary antioxidants and beneficial effect on oxidatively damaged DNA. Free Radic Biol Med 41:388–415

    Article  Google Scholar 

  48. Møller P, Loft S, Alfthan G, Freese R (2004) Oxidative DNA damage in circulating mononuclear blood cells after ingestion of blackcurrant juice or anthocyanin-rich drink. Mutat Res 551:119–126

    Google Scholar 

  49. Møller 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  Google Scholar 

  50. Møller P, Vogel U, Pedersen A, Dragsted LO, Sandström B, Loft S (2003) No effect of 600 g fruit and vegetables per day on oxidative DNA damage and repair in healthy human non-smokers. Cancer Epidemiol Biomarkers Prev 12:1016–1022

    Google Scholar 

  51. Nelson JL, Bernstein PS, Schmidt MC, Von Tress MS, Askew EW (2003) Dietary modification and moderate antioxidant supplementation differentially affect serum carotenoids, antioxidant levels and markers of oxidative stress in older humans. J Nutr 133:3117–3123

    CAS  Google Scholar 

  52. Olinski R, Gackowski D, Rozalski R, Foksinski M, Bialkowski K (2003) Oxidative DNA damage in cancer patients: a cause or a consequence of the disease development? Mutat Res 531:177–190

    CAS  Google Scholar 

  53. Pfeiffer JM, Askew EW, Roberts DE, Wood SM, Benson JE, Johnson SC, Freedman MS (1999) Effect of antioxidant supplementation on urine and blood markers of oxidative stress during extended moderate-altitude training. Wilderness Environ Med 10:66–74

    CAS  Google Scholar 

  54. Pool-Zobel BL, Adlercreutz H, Glei M, Liegibel UM, Sittlingon J, Rowland I, Wähälä K, Rechkemmer G (2000) Isoflavonoids and lignans have different potentials to modulate oxidative genetic damage in human colon cells. Carcinogenesis 21:1247–1252

    Article  CAS  Google Scholar 

  55. van Poppel G, Poulsen H, Loft S, Verhagen H (1995) No influence of beta carotene on oxidative DNA damage in male smokers. J Natl Cancer Inst 87:310–311

    Article  Google Scholar 

  56. Porkkala-Sarataho E, Salonen JT, Nyyssönen K, Kaikkonen J, Salonen R, Ristonmaa U, Diczfalusy U, Brigelius-Flohe R, Loft S, Poulsen HE (2000) Long-term effects of vitamin E, vitamin C, and combined supplementation of urinary 7-hydro-8-oxo-2′-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men. Arterioscle Thromb Vasc Biol 20:2087–2093

    CAS  Google Scholar 

  57. Prieme H, Loft S, Nyyssönen K, Salonen JT, Poulsen HE (1997) No effect of supplementation with vitamin E, ascorbic acid, or coenzyme Q10 on oxidative DNA damage estimated by 8-oxo-7,8-dihydro-2′-deoxyguanosine excretion in smokers. Am J Clin Nutr 65:503–507

    CAS  Google Scholar 

  58. Sacheck JM, Milbury PE, Cannon JG, Roubenoff R, Blumberg JB (2003) Effect of vitamin E and eccentric exercise on selected biomarkers of oxidative stress in young and elderly men. Free Radic Biol Med 34:1575–1588

    Article  CAS  Google Scholar 

  59. Schmidt MC, Askew EW, Roberts DE, Prior RL, Ensign Jr WY, Hesslink RE (2002) Oxidative stress in humans training in a cold, moderate altitude environment and their response to a phytochemical antioxidant supplementation. Wilderness Environ Med 13:94–105

    Google Scholar 

  60. Stewart RJ, Askew EW, McDonald CM, Metos J, Jackson WD, Balon TW, Prior RL (2002) Antioxidant status of young children: response to an antioxidant supplement. J Am Diet Assoc 102:1652–1657

    Article  CAS  Google Scholar 

  61. Subudhi AW, Jacobs KA, Hagobian TA, Fattor JA, Fulco CS, Muza SR, Rock PB, Hoffman AR, Cymerman A, Friedlander AL (2004) Antioxidant supplementation does not attenuate oxidative stress at high altitude. Aviat Space Environ Med 75:881–888

    CAS  Google Scholar 

  62. Sumida S, Doi T, Sakurai M, Yoshioka Y, Okamura K (1997) Effect of a single bout of exercise and β-carotene supplementation on the urinary excretion of 8-hydroxy-deoxyguanosine in humans. Free Radic Res 27:607–618

    Article  CAS  Google Scholar 

  63. Thompson HJ, Heimendinger J, Gillette C, Sedlacek SM, Haegele A, O’Neill C, Wolfe P (2005) In vivo investigation of changes in biomarkers of oxidative stress induced by plant food rich diets. J Agric Food Chem 53:6126–6132

    Article  CAS  Google Scholar 

  64. Toyokuni S, Okamoto K, Yodoi J, Haiai H (1995) Persistent oxidative stress in cancer. FEBS Lett 358:1–3

    Article  CAS  Google Scholar 

  65. Tuomainen TP, Loft S, Nyyssonen K, Punnonen K, Salonen JT, Poulsen HE (2007) Body iron is a contributor to oxidative damage of DNA. Free Radic Res 41:324–328

    Article  CAS  Google Scholar 

  66. Verhagen H, Poulsen HE, Loft S, van Poppel G, Willems MI, van Bladeren PJ (1995) Reduction of oxidative DNA-damage in humans by Brussels sprouts. Carcinogenesis 16:969–970

    Article  CAS  Google Scholar 

  67. Verhagen H, de Vries A, Nijhoff WA, Schouten A, van Poppel G, Peters WH, van den Berg H (1997) Effect of Brussels sprouts on oxidative DNA-damage in man. Cancer Lett 114:127–130

    Article  CAS  Google Scholar 

  68. Watanabe S, Haba R, Terashima K, Arai Y, Miura T, Chiba H, Takamatsu K (2000) Antioxidant activity of soya hypocotyl tea in humans. Biofactors 12:227–232

    CAS  Google Scholar 

  69. Weinbrenner T, Fito M, de la Torre R, Saez GT, Rijken P, Tormos C, Coolen S, Albaladejo MF, Abanades S, Schroder H, Marrugat J, Covas MI (2004) Olive oils high in phenolic compounds modulate oxidative/antioxidative status in men. J Nutr 134:2314–2321

    CAS  Google Scholar 

  70. World Cancer Research Fund/American Institute for Cancer Research (2007) Food, nutrition and the prevention of cancer: a global perspective. WCRF/AICR, Washington

    Google Scholar 

  71. Young JF, Dragsted LO, Haraldsdottir J, Daneshvar B, Kall MA, Loft S, Nilsson L, Mayer SE, Hyunh-Ba T, Hermetter A, Sandström B (2002) Green tea extracts only affects markers of oxidative stress postpradinally. Lasting antioxidant effect of flavonoid-free diet. Br J Nutr 87:343–355

    Article  CAS  Google Scholar 

Download references

Acknowledgment

This review was written as a part of the research integration in the Workpackage “Mechanisms of modulation of cancer by dietary factors” in the NoE Environmental Cancer risk, Nutrition and Individual Susceptibility (ECNIS, no. 513943; www.ecnis.org).”

Conflict of interest none.

Author information

Authors and Affiliations

  1. Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

    Steffen Loft & Peter Møller

  2. Øster Farimagsgade 5A, Postbox 2099 , 1014, Copenhagen K, Denmark

    Peter Møller

  3. University of Leicester, Leicester, UK

    Marcus S. Cooke

  4. Dept. of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

    Rafal Rozalski & Ryszard Olinski

Authors
  1. Steffen Loft
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Møller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcus S. Cooke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rafal Rozalski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ryszard Olinski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Møller.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loft, S., Møller, P., Cooke, M.S. et al. Antioxidant vitamins and cancer risk: is oxidative damage to DNA a relevant biomarker?. Eur J Nutr 47 (Suppl 2), 19–28 (2008). https://doi.org/10.1007/s00394-008-2004-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-008-2004-0

Key words

Search

Navigation