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Role of oxygen radicals in DNA damage and cancer incidence

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Abstract

The development of cancer in humans and animals is a multistep process. The complex series of cellular and molecular changes participating in cancer development are mediated by a diversity of endogenous and exogenous stimuli. One type of endogenous damage is that arising from intermediates of oxygen (dioxygen) reduction—oxygen-free radicals (OFR), which attacks not only the bases but also the deoxyribosyl backbone of DNA. Thanks to improvements in analytical techniques, a major achievement in the understanding of carcinogenesis in the past two decades has been the identification and quantification of various adducts of OFR with DNA. OFR are also known to attack other cellular components such as lipids, leaving behind reactive species that in turn can couple to DNA bases. Endogenous DNA lesions are genotoxic and induce mutations. The most extensively studied lesion is the formation of 8-OH-dG. This lesion is important because it is relatively easily formed and is mutagenic and therefore is a potential biomarker of carcinogenesis. Mutations that may arise from formation of 8-OH-dG involve GC → TA transversions. In view of these findings, OFR are considered as an important class of carcinogens. The effect of OFR is balanced by the antioxidant action of non-enzymatic antioxidants as well as antioxidant enzymes. Non-enzymatic antioxidants involve vitamin C, vitamin E, carotenoids (CAR), selenium and others. However, under certain conditions, some antioxidants can also exhibit a pro-oxidant mechanism of action. For example, β-carotene at high concentration and with increased partial pressure of dioxygen is known to behave as a pro-oxidant. Some concerns have also been raised over the potentially deleterious transition metal ion-mediated (iron, copper) pro-oxidant effect of vitamin C. Clinical studies mapping the effect of preventive antioxidants have shown surprisingly little or no effect on cancer incidence. The epidemiological trials together with in vitro experiments suggest that the optimal approach is to reduce endogenous and exogenous sources of oxidative stress, rather than increase intake of anti-oxidants. In this review, we highlight some major achievements in the study of DNA damage caused by OFR and the role in carcinogenesis played by oxidatively damaged DNA. The protective effect of antioxidants against free radicals is also discussed (Mol Cell Biochem 266: 37–56, 2004)

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References

  1. Halliwell B, Gutteridge JMC: Free Radicals in Biology and Medicine. Claredon Press, Oxford, 1989

    Google Scholar 

  2. Kehrer JP: Free-radicals as mediators of tissue-injury and disease. Crit Rev Toxicol 23: 21–48, 1993

    Google Scholar 

  3. Shen HM, Shi CY, Shen Y, Ong CN: Detection of elevated reactive oxygen species level in cultured rat hepatocytes treated with aflatoxin B-1. Free Rad Biol Med 2: 139–146, 1996

    Google Scholar 

  4. Ames NB, Shigenaga MK, Hagen TM: Oxidants, antioxidants, and the degenerative disease of aging. Proc Natl Acad Sci USA 90: 7915–7922, 1993

    Google Scholar 

  5. Halliwell B, Gutteridge JMC, Cross CE: Free-radicals, antioxidants, and human-disease — Where are we now. J Lab Clin Med 119: 598–620, 1992

    Google Scholar 

  6. Ward JF, Limoli CL, Calabro-Jones P, Evans JW: Radiation versus chemical damage to DNA. In: P.A. Ceruti, O.F. Nygaard, M.G. Simic (eds). Anticarcinogenesis and Radiation Protection. Plenum, New York, 1988, pp 321–327

    Google Scholar 

  7. Esterbauer H, Eckl P, Ortner A: Possible mutagens derived from lipids and lipid precursors. Mutat Res 238: 223–233, 1990

    Google Scholar 

  8. Bartsch H: DNA adducts in human carcinogenesis: Etiological relevance and structure-activity relationship. Mut Res Rev Genet Toxicol 340: 67–79, 1996

    Google Scholar 

  9. Winterbourn CC: Superoxide as an intracellular radical sink. Free Rad Biol Med 14: 85–90, 1993

    Google Scholar 

  10. Liochev SI, Fridovich I: The role of o-2-center-dot-in the production of ho-center-dot-in-vitro and in-vivo. Free Rad Biol Med 16: 29–33, 1994

    Google Scholar 

  11. Miller DM, Buettner GR, Aust SD: Transition-metals as catalysts of autoxidation reactions. Free Rad Biol Med 8: 95–108, 1990

    Google Scholar 

  12. Symons MCR: Chemical and Biochemical Aspects of Electron-Spin-Resonance spectroscopy, Van Nostrand, Reinhold, 1978

    Google Scholar 

  13. Bard AJ, Parsons R, Jordan J: Standard Potentials in Aqueous Solutions. IUPAC. Marcel Dekker, New York, USA, 1985

    Google Scholar 

  14. Wardman P: Reduction potentials of one-electron couples involving free radicals in aqueous solution. J Phys Chem Ref Data 18: 1637–1755, 1989

    Google Scholar 

  15. Fridovich I: Biological effects of the superoxide radical. Arch Biochem Biophys 247: 1–11, 1986

    Google Scholar 

  16. Salvador A, Sousa J, Pinto RE: Hydroperoxyl, superoxide and pH gradients in the mitochondrial matrix: A theoretical assessment. Free Rad Biol Med 31: 1208–1215, 2001

    Google Scholar 

  17. Hanukoglu I, Rapoport R, Weiner L, Sklan D: Electron leakage from the mitochondrial NADPH-adrenodoxin reductase-adrenodoxin-p450scc (cholesterol side-chain cleavage) system. Arch Biochem Bio-phys 305: 489–498, 1993

    Google Scholar 

  18. Benzi G, Pastoris O, Marzatico F, Villa RF, Dagani F, Curti D: The mitochondrial electron-transfer alteration as a factor involved in the brain aging. Neurobiol Aging 13: 361–368, 1992

    Google Scholar 

  19. Freeman BA, Crapo JD: Free-radicals and tissue-injury. Lab Invest 47: 412–426, 1982

    Google Scholar 

  20. Kinnula VL, Crapo JD, Raivio KO: Biology of disease-generation and disposal of reactive oxygen metabolites in the lung. Lab Invest 73: 3–19, 1995

    Google Scholar 

  21. Brookes PS, Levonen AL, Shiva S, Sarti P, Darley-Usmar VM, Mitochondria: Regulators of signal transduction by reactive oxygen and nitrogen species. Free Rad Biol Med 33: 755–764, 2002

    Google Scholar 

  22. Butler J, Hoey BM: The one-electron reduction potential of several substrates can be related to their reduction rates by cytochrome-P-450 reductase. Biochim Biophys Acta 1161: 73–78, 1993

    Google Scholar 

  23. Thannickal VJ, Fanburg BL: Reactive oxygen species in cell signaling. Am J Physiol-Lung cell Mol Physiol 279: L1005–L1028, 2000

    Google Scholar 

  24. Moriwaki Y, Yamamoto T, Higashino K: Enzymes involved in purine metabolism — A review of histochemical localization and functional implications. Histol Histopathol 14: 1321–1340, 1999

    Google Scholar 

  25. Harrison R: Structure and function of xanthine oxidoreductase: Where are we now? Free Rad Biol Med 33: 774–797, 2002.

    Google Scholar 

  26. Borges F, Fernandes E, Roleira F: Progress towards the discovery of xanthine oxidase inhibitors. Curr Med Chem 9: 195–217, 2002

    Google Scholar 

  27. Stohs SJ, Bagchi D: Oxidative mechanisms in the toxicity of metal-ions. Free Rad Biol Med 18: 321–336, 1995

    Google Scholar 

  28. Fahl WE, Lalwani ND, Watanabe T, Goel SK, Reddy JK: DNA damage related to increased hydrogen-peroxide generation by hypolipidemic drug-induced liver peroxisomes. Proc Natl Acad Sci USA; Biol. Sci. 81: 7827–7830, 1984

    Google Scholar 

  29. Thannickal VJ, Fanburg BL: Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 279: L1005–L1028, 2000

    Google Scholar 

  30. Vignais PV: The superoxide-generating NADPH oxidase: Structural aspects and activation mechanism. Cell Mol Life Sci 59: 1428–1459, 2002

    Google Scholar 

  31. Van Heerebeek L, Meischl C, Stooker W, Meijer CLJM, Niessen HWM, Roos D: NADPH oxidase(s): New source(s) of reactive oxygen species in the vascular system? J Clin Pathol 55: 561–568, 2002

    Google Scholar 

  32. Jirapongsananuruk O, Malech HL, Kuhns DB, Niemela JE, Brown MR, Anderson-Cohen M, Fleisher TA: Diagnostic paradigm for evaluation of male patients with chronic granulomatous disease, based on the dihydrorhodamine 123 assay. J Allergy Clin Immun 111:374–379, 2003

    Google Scholar 

  33. Proctor PH: Free Radicals and Human Disease, vol 1. CRC Handbook of Free Radicals and Antioxidants, 1989, pp 209–221

  34. Rodriguez AM, Carrico PM, Mazurkiewicz JE, Melendez JA: Mitochondrial or cytosolic catalase reverses the MnSOD-dependent inhibition of proliferation by enhancing respiratory chain activity, net ATP production, and decreasing the steady state levels of H2O2. Free Rad Biol Med 29: 801–813, 2000

    Google Scholar 

  35. Prutz WA, Butler J, Land EJ: The glutathione free-radical equilibrium, gs(.) +gs(-reversible-arrow-gss(.-)g, mediating electron-transfer to fe(iii)-cytochrome-c. Biophys Chem 49: 101–111, 1994

    Google Scholar 

  36. Prousek J: Fenton reaction after a century. Chem Listy 89: 11–21, 1995

    Google Scholar 

  37. Kalyanaraman B, Morehouse KM, Mason RP: An electron-paramag-netic resonance study of the interactions between the adriamycin semiquinone, hydrogen-peroxide, iron-chelators, and radical scavengers. Arch Biochem Biophys 286: 164–170, 1991

    Google Scholar 

  38. Buettner GR, Jurkiewicz BA: Catalytic metals, ascorbate and free radicals: Combinations to avoid. Rad Res 145: 532–541, 1996

    Google Scholar 

  39. Shi XL, Chiu A, Chen CT, Halliwell B, Castranova V, Vallyathan V: Reduction of chromium(VI) and its relationship to carcinogenesis. J Toxicol Environ Health B Crit Rev 2: 87–104, 1999

    Google Scholar 

  40. Klug-Roth D, Rabani J: Pulse radiolytic studies on reactions of aqueous superoxide radicals with copper(II) complexes. J Phys Chem 80: 588–591, 1976

    Google Scholar 

  41. Stohs SJ, Bagchi D: Oxidative mechanisms in the toxicity of metal-ions. Free Rad Biol Med 18: 321–336, 1995

    Google Scholar 

  42. Balasubramanian B, Pogozelski WK, Tullius TD: DNA strand breaking by the hydroxyl radical is governed by the accessible surface areas of the hydrogen atoms of the DNA backbone. Proc Natl Acad Sci USA 95: 9738–9743, 1998

    Google Scholar 

  43. Agatsuma S, Nagoshi T, Kobayashi M, Usa M, Watanabe H, Sekino H, Inaba H: Hydroxyl radical-induced characteristic chemiluminescent spectra from plasma of hemodialysis-patients. Clin Chem 38: 48–55, 1992

    Google Scholar 

  44. Schafer FQ, Qian SY, Buettner GR: Iron and free radical oxidations in cell membranes. Cell Mol Biol 46: 657–662, 2000

    Google Scholar 

  45. Hempel SL, Buettner GR, Wessels DA, Galvan GM, Omalley YQ: Extracellular iron(II) can protect cells from hydrogen peroxide. Arch Biochem Biophys 330: 401–408, 1996

    Google Scholar 

  46. Lloyd RV, Hanna PM, Mason RP: The origin of the hydroxyl radical oxygen in the Fenton reaction. Free Rad Biol Med 22: 885–888, 1997

    Google Scholar 

  47. Reddy S, Halliwell B, Jones AD, Longhurst JC: The use of phenylalanine to detect hydroxyl radical production in vivo: A cautionary note. Free Rad Biol Med 27: 1465–1465, 1999

    Google Scholar 

  48. Halliwell B, Clement MV, Ramalingam J, Long LH: Hydrogen peroxide. Ubiquitous in cell culture and in vivo? IUBMB Life 50: 251–257, 2000

    Google Scholar 

  49. Kadiiska MB, Mason RP: In vivo copper-mediated free radical production: An ESR spin-trapping study. Spectrochim Acta A, Mol Biomol Spectr 58: 1227–1239, 2002

    Google Scholar 

  50. Toyokuni S: Iron and carcinogenesis: From Fenton reaction to target genes. Redix Rep 7: 189–197, 2002

    Google Scholar 

  51. Imlay JA, Park S, Woodmansee A: What is the intracellular reductant that drives the fenton reaction? Free Rad Biol Med 33(suppl 2): 255, 2002

    Google Scholar 

  52. Raleigh JA, Shum FY: Hydroxyl radical scavengers and membrane damage — Supplementary role for alpha-tocopherol in scavenging secondary radicals. Rad Res 94: 664–665, 1983

    Google Scholar 

  53. Zastawny TH, Altman SA, Randerseichhorn L, Madurawe R, Lumpkin JA, Dizdaroglu M, Rao G: DNA-base modifications and membrane damage in cultured-mammalian-cells treated with iron ions. Free Rad Biol Med 18: 1013–1022, 1995

    Google Scholar 

  54. Mao H, Deng ZW, Wang F, Harris TM, Stone MP: An intercalated and thermally stable FAPY adduct of aflatoxin B-1 in a DNA duplex: Structural refinement from H-1 NMR. Biochemistry 37: 4374–4387, 1998

    Google Scholar 

  55. Boiteux S, Radicella JP: The human OGG1 gene: Structure, functions, and its implication in the process of carcinogenesis. Arch Biochem Biophys 377: 1–8, 2000

    Google Scholar 

  56. Jaruga PW, Rodriguez H, Dizdaroglu M: Measurement of 8-hydroxy-2-deoxyadenosine in DNA by liquid chromatography/mass spectrom-etry. Free Rad Biol Med 31: 336–344, 2001

    Google Scholar 

  57. Dizdaroglu M, Olinski R, Doroshow JH, Akman SA: Modification of DNA bases in chromatin of intact target human-cells by activated human polymorphonuclear leukocytes. Cancer Res 53: 1269–1272, 1993

    Google Scholar 

  58. Murata M, Imada M, Inoue S, Kawanishi S: Metal-mediated DNA damage induced by diabetogenic alloxan in the presence of NADH. Free Rad Biol Med 25: 586–595, 1998

    Google Scholar 

  59. Reiter RJ, Acuna-Castroviejo D, Tan DX, Burkhardt S: Free radical-mediated molecular damage-Mechanisms for the protective actions of melatonin in the central nervous system. Neuroprot Agents Annals NY Acad Sci 939: 200–215, 2001

    Google Scholar 

  60. Gichner T: DNA damage induced by indirect and direct acting mutagens in catalase-deficient transgenic tobacco—Cellular and acellular Comet assays, Mut Fres Genet Toxicol Environ Mutagen 535: 187–193, 2003

    Google Scholar 

  61. Mistry N, Podmore L, Cooke M, Butler P, Griffiths H, Herbert K, Lunec J: Novel monoclonal antibody recognition of oxidative DNA damage adduct, deoxycytidine-glyoxal. Lab Invest 83: 241–250, 2003

    Google Scholar 

  62. Rodriguez H, Valentine MR, Holmquist GP, Akman SA, Termini J: Mapping of peroxyl radical induced damage on genomic DNA. Biochemistry 38: 16578–16588, 1999

    Google Scholar 

  63. Chen CJ, Bozzelli JW: Thermochemical property, pathway and kinetic analysis on the reactions of allylic isobutenyl radical with O-2: An elementary reaction mechanism for isobutene oxidation. J Phys Chem A 104: 9715–9732, 2000

    Google Scholar 

  64. Hawkins CL, Davies MJ: Generation and propagation of radical reactions on proteins. Biochim Biophys Acta Bioenerg 1504: 196–219, 2001

    Google Scholar 

  65. Korytowski W, Zareba M, Girotti AW: Inhibition of free radical-mediated cholesterol peroxidation by diazeniumdiolate-derived nitric oxide: Effect of release rate on mechanism of action in a membrane system. Chem Res Toxicol 13: 1265–1274, 2000.

    Google Scholar 

  66. Kanazawa A, Sawa T, Akaike T, Maeda H, Dietary lipid peroxidation products and DNA damage in colon carcinogenesis. Eur J Lipid Sci Technol 104: 439–447, 2002

    Google Scholar 

  67. Razskazovskii Y, Sevilla MD: Reactions of sulphonyl peroxyl radicals with DNA and its components: Hydrogen abstraction from the sugar backbone versus addition to pyrimidine double bonds. Int J Radiat Biol 69: 75–87, 1996

    Google Scholar 

  68. Basaga HS: Biochemical aspects of free-radicals. Biochem Cell Biol-Biochimie et Biologie Cellulaire 68: 989–998, 1990

    Google Scholar 

  69. Alfassi ZB: The Chemistry of Free Radicals: Peroxyl Radicals. Wiley, New York, 1997, pp 546

    Google Scholar 

  70. Khan N, Swartz H: Measurements in vivo of parameters pertinent to ROS/RNS using EPR spectroscopy. Mol Cell Biochem 234–235: 341–357, 2002

    Google Scholar 

  71. Halliwell B, Aruoma OI: DNA damage by oxygen-derived species-Its mechanism and measurement in mammalian systems. FEBS Lett 281: 9–19, 1991

    Google Scholar 

  72. Wang D, Kreutzer DA, Essigmann JM: Mutagenicity and repair of oxidative DNA damage: Insights from studies using defined lesions. Mutat Res Fundam Mol Mech Mutagen 400: 99–115, 1998

    Google Scholar 

  73. Dizdaroglu M, Jaruga P, Birincioglu M, Rodriguez H: Free radical-induced damage to DNA: Mechanisms and measurement. Free Rad Biol Med 32: 1102–1115, 2002

    Google Scholar 

  74. Jaruga P, Dizdaroglu M: Repair of products of oxidative DNA base damage in human cells. Nucl Acid Res 24: 1389–1394, 1996

    Google Scholar 

  75. Marnett LJ, Oxyradicals and DNA damage. Carcinogenesis 21: 361–370, 2000

    Google Scholar 

  76. Dreher D, Junod AF: Role of oxygen free radicals in cancer development. Eur J Cancer 32A: 30–38, 1996

    Google Scholar 

  77. Wallace SS: Enzymatic processing of radiation-induced free radical damage in DNA. Radiat Res 150: S60–S79, 1998

    Google Scholar 

  78. Crawford DR, Edbauer-Nechamen CA, Schools GP, Salmon SL, Davies JMS and Davies KJA: Oxidant-modulated gene expression. In: Davies and Ursini (eds). The Oxygen Paradox, 1995, pp 327–335

  79. Bohr VA, Taffe BG, Larminat F: DNA repair, oxidative stress and aging. In: R.G. Cutler, L. Packer, A. Bertram, A. Mori (eds). Oxidative Stress and Aging. Birkhauser Verlag Basel, Switzerland, 1995, pp 101–110

    Google Scholar 

  80. Cerutti PA, Trump BF: Inflammation and oxidative stress in carcino-genesis. Cancer Cells 3: 1–7, 1991

    Google Scholar 

  81. Lander HM, Ogiste JS, Teng KK, Novogrodsky A. p21ras as a common signaling target of reactive free radicals and cellular redox stress. J Biol Chem 270: 21195–21198, 1995

    Google Scholar 

  82. Guyton KZ, Kensler TW. Oxidative mechanisms in carcinogenesis. Br Med Bull 49: 523–544, 1993

    Google Scholar 

  83. Cerda S, Weitzman SA: Influence of oxygen radical injury on DNA methylation. Mut Res Rev Mutat Res 386: 141–152, 1997

    Google Scholar 

  84. Bohr VA, Taffe BG, Larminat F: DNA repair, oxidative stress and ag-ing. In: R.G. Cutler, L. Packer, J. Bertram, A. Mori (eds). Oxidative Stress and Aging. Birkhauser Verlag Basel, Switzerland, 1995, pp 101–110

    Google Scholar 

  85. Jackson JH: Potential molecular mechanisms of oxidant-induced carcinogenesis. Environ Health Perspect 102: 155–158, 1994

    Google Scholar 

  86. Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P: Mutations in the p53 gene occur in diverse human tumor types. Nature 342: 705–708, 1989

    Google Scholar 

  87. Yandell DW, Campbell TA, Dayton SH, Petersen R, Walton D, Little JB, McConkie-Rosell A, Buckle EG, Dryja TP: Oncogenic point mu-tations in the human retinoblastoma gene: Their application to genetic counseling. N Engl J Med 321: 1689–1695, 1989

    Google Scholar 

  88. Valko M, Morris H, Mazur M, Rapta P, Bilton RF: Oxygen free radical generating mechanisms in the colon: Do the semiquinones of vitamin K play a role in the aetiology of colon cancer? Biochim Biophys Acta Gen Subj 1527: 161–166, 2001

    Google Scholar 

  89. Brezova V, Valko M, Breza M, Morris H, Telser J, Dvoranova D, Kaiserova K, Varecka L, Mazur M, Leibfritz D: Role of radicals and singlet oxygen in photoactivated DNA cleavageby the anticancer drug camptothecin: Anelectron paramagnetic resonance study. J Phys Chem B 107: 2415–2425, 2003

    Google Scholar 

  90. Lombardi V, Valko L, Stolc S, Valko M, Ondrejickova O, Horakova L, Placek J, Troncone A: Free radicals in rabbit spinal cord ischemia: Electron spin resonance spectroscopy and correlation with SOD activity. Cell Mol Neurobiol 18: 399–412, 1998

    Google Scholar 

  91. Stolc S, Valko L, Valko M, Lombardi V: A technique for the fast sampling of biological tissues for electron paramagnetic resonance spectroscopy. Free Rad Biol Med 20: 89–91, 1996

    Google Scholar 

  92. Dizdaroglu M, Jaruga P, Birincioglu M, Rodriguez H: Free radical-induced damage to DNA: Mechanisms and measurement. Free Rad Biol Med 32, 1102–1115, 2002

    Google Scholar 

  93. von Sonntag C: The Chemical Basis of Radiation Biology. Taylor and Francis, New York, 1987

    Google Scholar 

  94. Dizdaroglu M: Oxidative damage to DNA in mammalian chromatin. Mutat Res 275: 331–342, 1992

    Google Scholar 

  95. Breen AP, Murphy JA: Reactions of oxyl radicals with DNA. Free Rad Biol Med 18: 1033–1077, 1995

    Google Scholar 

  96. Steenken S: Purine bases, nucleosides, and nucleotides: Aqueous solution redox chemistry and transformation reactions of their radical cations and e and OH adducts. Chem Rev 89: 503–520, 1989

    Google Scholar 

  97. Vieira AJSC, Candeias LP, Steenken S: Hydroxyl radical-induced damage to the purine-bases of DNA — In vitro studies. J Chim Phys 90: 881–897, 1993

    Google Scholar 

  98. Breen AP, Murphy JA: Reactions of oxyl radicals with DNA. Free Rad Biol Med 18: 1033–1077, 1995

    Google Scholar 

  99. Lu CY, Yao S, Han ZH, Lin WZ, Wang WF, Zhang WL, Lin NY: Reaction of reducing hydroxyl radical adducts of pyrimidine nucleotides with riboflavin and flavin adenine dinucleotide (FAD) via electron transfer: A pulse radiolysis study. Biophys Chem 85: 17–24, 2000

    Google Scholar 

  100. Shigenaga MK, Gimeno CJ, Ames BN: Urinary 8-hydroxy-2'-deoxyguanosine as a biological marker of in vivo oxidative DNA damage. Proc Natl Acad Sci USA 86: 9697–9701, 1989

    Google Scholar 

  101. Grollman AP, Moriya M: Mutagenesis by 8-oxoguanine: An enemy within. Trends Genet 9: 246–249, 1993

    Google Scholar 

  102. Dizdaroglu M: Mechanisms of free radical damage to DNA. In:O.I. Aruoma, B. Halliwell (eds). DNA and Free Radicals: Techniques, Mechanisms and Applications. OICA International, St. Lucia, 1998, pp 3–26

    Google Scholar 

  103. Collins A, Cadet J, Epe B, Gedik C: Problems in the measurement of 8-oxoguanine in human DNA. Report of a workshop, DNA oxidation, held in Aberdeen, UK, 19–21 January, 1997. Carcinogenesis 18: 1833–1836, 1997

    Google Scholar 

  104. Grollman AP, Moriya M: Mutagenesis by 8-oxoguanine: An enemy within. Trends Genet 9: 246–249, 1993

    Google Scholar 

  105. Lunec J: ESCODD: European Standards Committee on Oxidative DNA Damage. Free Rad Res 29: 601–608, 1998

    Google Scholar 

  106. ESCODD: Comparison of different methods of measuring 8-oxoguanine as a marker of oxidative DNA damage. Free Rad Res 32: 333–341, 2000

    Google Scholar 

  107. Cooke MS, Lunec J, Evans MD: Progress in the analysis of urinary oxidative DNA damage. Free Rad Biol Med 33: 1601–1614, 2002

    Google Scholar 

  108. Bruner SD, Norman DPG, Verdine GL: Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature 403: 859–866, 2000

    Google Scholar 

  109. Kasai H, Chemistry-based studies on oxidative DNA damage: Formation, repair, and mutagenesis. Free Rad Biol Med 33: 450–456, 2002.

    Google Scholar 

  110. Lunec J, Holloway KA, Cooke MS, Faux S, Griffiths HR, Evans MD: Urinary 8-oxo-2-deoxyguanosine: Redox regulation of DNA repair in vivo? Free Rad Biol Med 33: 875–885, 2002

    Google Scholar 

  111. Asami S, Hirano T, Yamaguchi R, Tsurudome Y, Itoh H, Kasai H: Effects of forced and spontaneous exercise on 8-hydroxydeoxyguanosine levels in rat organs. Biochem Biophys Res Commun 243: 678–682, 1998

    Google Scholar 

  112. Inoue M, Kamiya H, Fujikawa K, Ootsuyama Y, Murata-Kamiya N, Osaki T, Yasumoto K, Kasai H: Induction of chromosomal gene mutations in Escherichia coli by direct incorporation of oxidatively damaged nucleotides—New evaluation method for mutagenesis by damaged DNA precursors in vivo. J Biol Chem 273: 11069–11074, 1998

    Google Scholar 

  113. Fujikawa K, Kamiya H, Yakushiji H, Nakabeppu Y, Kasai H: Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP. Nucleic Acids Res 29: 449–454, 2001

    Google Scholar 

  114. Floyd RA: Measurement of oxidative stress in vivo. In: K.A.J. Davies (ed). Proceedings of the First Oxygen Society Meeting. Pergamon Press, New York, 1994, pp 79–84

    Google Scholar 

  115. Porter NA: Mechanisms for the autooxidation of polyunsatrurated lipids. Acc Chem Res 19: 262–268, 1986

    Google Scholar 

  116. Tang DG, La EH, Kern J, Kehrer JP: Fatty acid oxidation and signaling in apoptosis. Biol Chem 383: 425–442, 2002

    Google Scholar 

  117. Devries CEE, Van Noorden CJF: Effects of dietary fatty-acid com-position on tumor-growth and metastasis. Antic Res 12: 1513–1522, 1992

    Google Scholar 

  118. Zollner H, Esterbauer H, Schauenstein E: Relationship between chemical constitution and therapeutic activity of alpha, beta-unsaturated aldehydes in Ehrlich-solid-tumor of mouse. Zeit Krebs Klin Onkol 83: 27–30, 1975

    Google Scholar 

  119. Basu AK, Marnett LJ: Unequivocal demonstration that malondialdehyde is a mutagen. Carcinogenesis 4: 331–333, 1983

    Google Scholar 

  120. Yau TM: Mutagenicity and cytotoxicity of malonaldehyde in mammalian-cells. Mech Ageing Dev 11: 137–144, 1979

    Google Scholar 

  121. Marnett LJ: Lipid peroxidation — DNA damage by malondialdehyde. Mut Res Fund Mol Mech Mutagen 424: 83–95, 1999

    Google Scholar 

  122. Mao H, Schnetz-Boutaud NC, Weisenseel JP, Marnett LJ, Stone MP: Duplex DNA catalyzes the chemical rearrangement of a malondialdehyde deoxyguanosine adduct. Proc Natl Acad Sci USA96: 6615–6620, 1999

    Google Scholar 

  123. Nath RG, Chung FL, Detection of exocyclic 1, n- 2 propanodeoxyguanosine adducts as common DNA lesions in rodents and humans. Proc Natl Acad Sci USA 91: 7491–7495, 1994

    Google Scholar 

  124. Kawanishi M, Matsuda T, Nakayama A, Takebe H, Matsui S, Yagi T: Molecular analysis of mutations induced by acrolein in human fibroblast cells using supf shuttle vector plasmids. Mut Res Gen Toxicol Environ Mutagen 417: 65–73, 1998

    Google Scholar 

  125. Johnson KA, Fink SP, Marnett LJ: Repair of propanodeoxyguanosine by nucleotide excision repair in vivo and in vitro. J Biol Chem 272: 11434–11438, 1997

    Google Scholar 

  126. Fedtke N, Boucheron JA, Walker VE, Swenberg JA: Vinyl chloride-induced DNA adducts: 2. Formation and persistence of 7-(2'-oxoethyl) guanine and n2, 3-ethenoguanine in rat-tissue DNA. Carcinogenesis 11: 1287–1292, 1990

    Google Scholar 

  127. Basu AK, Wood ML, Niedernhofer LJ, Ramos LA, Essigmann JM: Mutagenic and genotoxic effects of 3-vinyl chloride-induced DNA lesions-1, n(6)-Ethenoadenine, 3, n(4)-ethenocytosine, and 4-amino-5-(imidazol-2-yl)imidazole. Biochemistry 32: 12793–12801, 1993

    Google Scholar 

  128. Moriy AM, Zhang W, Johnson F, Grollman AP: Mutagenic potency of exocyclic DNA-adducts — Marked differences between Escherichia coli and simian kidney-cells. Proc Natl Acad Sci USA 91(25): 11899–11903, 1994

    Google Scholar 

  129. Pandya GA, Moriya M: 1, N-6-Ethenodeoxyadenosine, a DNA adduct highly mutagenic in mammalian cells. Biochemistry 35: 11487–11492, 1996

    Google Scholar 

  130. Coussens LM, Werb Z: Inflammation and cancer. Nature 420: 860–867, 2002

    Google Scholar 

  131. Shacter F, Weitzman SA: Chronic inflammation and cancer. Oncology 16: 217–222, 2002

    Google Scholar 

  132. Chisari FV, Ferrari C: Hepatitis-b virus immunopathology. Springer Sem Immunopathol 17: 261–281, 1995

    Google Scholar 

  133. Naito Y, Yoshikawa T: Molecular and cellular mechanisms involved in Helicobacter pylori-induced inflammation and oxidative stress. Free Rad Biol Med 33: 323–336, 2002

    Google Scholar 

  134. Bianchini F, Jaeckel A, Vineis P, Martinez-Garcia C, Elmstahl S, van Kappel AL, Boeing H, Ohshima H, Riboli E, Kaaks R: Inverse correlation between alcohol consumption and lymphocyte levels of 8-hydroxydeoxyguanosine in humans. Carcinogenesis 22: 885–890, 2001

    Google Scholar 

  135. Nia AB, Van Schooten FJ, Schilderman PAEL, De Kok TMCM, Haenen GR, Van Herwijnen MHM, Van Agen E, Pachen D, Kleinjans JCS: A multi-biomarker approach to study the effects of smoking on oxidative DNA damage and repair and antioxidative defense mechanisms. Carcinogenesis 22: 395–401, 2001

    Google Scholar 

  136. Demple B, Harrison L: Repair of oxidative damage to DNA: Enzymology and biology. Ann Rev Biochem 63: 915–948, 1994

    Google Scholar 

  137. Kasai H, Crain PF, Kuchino Y, Nishimura S, Ootsuyama A, Tanooka H: Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair. Carcinogenesis 7: 1894–1851, 1986

    Google Scholar 

  138. Chung MH, Kasai H, Jones DS, Inoue H, Ishikawa H, Otsuka E, Nishimura S. An endonuclease activity of Escherichia coli that specifically removes 8-hydroxyguanine residues from DNA. Mutat Res 254: 1–12, 1991

    Google Scholar 

  139. Boiteux S, O'Connor TR, Laval J: Formamidopyrimidine-DNA glycosylase of Escherichia coli: Cloning and sequencing of the fpg structural gene and overproduction of the protein. EMBO J 6: 3177–3183, 1987

    Google Scholar 

  140. Tchou J, Kasai H, Shibutani S, Chung M-H, Laval J, Grollman AP, Nishimura S: 8-Oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity. Proc Natl Acad Sci USA 88: 4690–4694, 1991

    Google Scholar 

  141. Michaels ML, Tchou J, Grollman AP, Miller JH: A repair system for 8-oxo 7, 8-dihydrodeoxyguanine. Biochemistry 31: 10964–10968, 1992

    Google Scholar 

  142. Maki H, Sekiguchi M: Mut T protein specifically hydrolyzes a potent mutagenic substrate for DNA synthesis. Nature 355: 273–275, 1992

    Google Scholar 

  143. Tajiri T, Maki H, Sekiguchi M: Functional cooperation of MutT, MutM and MutY proteins in preventing mutations caused by spontaneous oxidation of guanine nucleotide in Escherichia coli. Mutat Res 336: 257–267, 1995

    Google Scholar 

  144. Bessho T, Tano K, Kasai H, Otsuka E, Nishimura S: Evidence for two DNA repair enzymes for 8-hy-droxyguanine 7, 8-dihydro-8-oxoguanine in human cells. J Biol Chem 268: 19416–19421, 1993

    Google Scholar 

  145. Laval F, Wink DA, Laval J: A discussion of mechanisms of NO genotoxicity: Implication of inhibition of DNA repair proteins. Rev Physiol Biochem Pharmacol 131: 175–191, 1997

    Google Scholar 

  146. Blokhina O, Virolainen E, Fagerstedt KV: Antioxidants, oxidative damage and oxygen deprivation stress: Areview. Ann Bot 91: 179–194, 2003

    Google Scholar 

  147. Knight JA, Review: Free radicals, antioxidants, and the immune system. Ann Clinic Lab Sci 30: 145–158, 2000

    Google Scholar 

  148. La Vecchia C, Altieri A, Tavani A: Vegetables, fruit, antioxidants and cancer: A review of Italian studies. Eur J Nutr 40: 261–267, 2001

    Google Scholar 

  149. Emmert DH, Kirchner JT: The role of vitamin E in the prevention of heart disease. Arch Fam Med 8: 537–542, 1999.

    Google Scholar 

  150. Kondo K, Kurihara M, Fukuhara K: Mechanism of antioxidant effect of catechins. Flavon Polyphen Methods Enzymol 335: 203–217, 2001

    Google Scholar 

  151. Ursini F, Tubaro F, Rong J, Sevanian A: Optimization of nutrition: Polyphenols and vascular protection. Nutr Rev 57: 241–249, 1999

    Google Scholar 

  152. Russell RM:Beta-carotene and lung cancer. Pure Appl Chem 74: 1461–1467, 2002

    Google Scholar 

  153. Holick CN, Michaud DS, Stolzenberg-Solomon R, Mayne ST, Pietinen P, Taylor PR, Virtamo J, Albanes D: Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the alpha-tocopherol, beta-carotene cohort study. Am J Epidemiol 156: 536–547, 2002

    Google Scholar 

  154. Brekelmans CTM: Risk factors and risk reduction of breast and ovarian cancer. Curr Opin Obserics Gynecol 15: 63–68, 2003

    Google Scholar 

  155. Terry P, Jain M, Miller AB, Howe GR, Rohan TE: Dietary carotenoids and risk of breast cancer. Am J Clinic Nutr 76: 883–888, 2002

    Google Scholar 

  156. Ward MH, Cantor KP, Riley D, Merkle S, Lynch CF: Nitrate in public water supplies and risk of bladder cancer. Epidemiology 14: 183–190, 2003

    Google Scholar 

  157. Fang YZ, Yang S, Wu GY: Free radicals, antioxidants, and nutrition. Nutrition 18: 872–879, 2002

    Google Scholar 

  158. Griffiths HR, Lunec J: Ascorbic acid in the 21st century — More than a simple antioxidant. Environ Toxicol Pharmacol 10: 173–182, 2001

    Google Scholar 

  159. Shang F, Lu M, Dudek E, Reddan J, Taylor A: Vitamin C and vitamin E restore the resistance of GSH-depleted lens cells to H2O2. Free Rad Biol Med 34: 521–530, 2003

    Google Scholar 

  160. Zhang SM, Hernan MA, Chen H, Spiegelman D, Willett WC, Ascherio A: Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk. Neurology 59: 1161–1169, 2002

    Google Scholar 

  161. Flagg EW, Coates RJ, Greenberg RS: Epidemiologic studies of antioxidants and cancer in humans. J Am Coll Nutr 14: 419–427, 1995

    Google Scholar 

  162. Buettner GR, Jurkiewicz BA: Ascorbate free radical as a marker of oxidative stress: An EPR study. Free Rad Biol Med 14: 49–55, 1993

    Google Scholar 

  163. Mukai K, Nishimura M, Kikuchi S: Stopped-flow investigation of the reaction of vitamin-c with tocopheroxyl radical in aqueous triton x-100 micellar solutions — The structure-activity relationship of the regeneration reaction of tocopherol by vitamin-c. J Biol Chem 266: 274–278, 1991

    Google Scholar 

  164. Buettner GR, Jurkiewicz BA: Catalytic metals, ascorbate and free radicals: Combinations to avoid. Radiat Res 145: 532–541, 1996

    Google Scholar 

  165. Berger TM, Polidori MC, Dabbagh A, Evans PJ, Halliwell B, Morrow JD, Roberts LJ, Frei B: Antioxidant activity of vitamin C in iron-overloaded human plasma. J Biol Chem 272: 15656–15660, 1997

    Google Scholar 

  166. Kašparová S, Brezová V, Valko M, Horecký J, Mlynárik V, Liptaj T, Van ýová O, Uliýná O, Dobrota D: Investigation of creatine kinase reaction, free radical formation and oxidative phosphorylation in model of chronic ischemia in aged-rat brains. Cell Mol Neurobiol, (in press)

  167. Frei B: Cardiovascular-disease and nutrient antioxidants — Role of low-density-lipoprotein oxidation. Critic Rev Food Sci Nutr 35: 83–98, 1995

    Google Scholar 

  168. Siow RCM, Sato H, Leake DS, Ishii T, Bannai S, Mann GE: Induction of antioxidant stress proteins in vascular endothelial and smooth muscle cells: Protective action of vitamin C against atherogenic lipoproteins. Free Rad Res 31: 309–318, 1999

    Google Scholar 

  169. Retsky KL, Freeman MW, Frei B: Ascorbic-acid oxidation product(s) protect human low-density-lipoprotein against atherogenic modification — Antioxidant rather than prooxidant activity of vitamin-c in the presence of transition-metal ions. J Biol Chem 268: 1304–1309, 1993

    Google Scholar 

  170. Retsky KL, Chen K, Zeind J, Frei B: Inhibition of copper-induced LDL oxidation by vitamin C is associated with decreased copper-binding to LDL and 2-oxo-histidine formation. Free Rad Biol Med 26: 90–98, 1999

    Google Scholar 

  171. Zhang HM, Wakisaka N, Maeda O, Yamamoto T: Vitamin C inhibits the growth of a bacterial risk factor for gastric carcinoma: Helicobacter pylori. Cancer 80: 1897–1903, 1997

    Google Scholar 

  172. Schumann K: Interactions between drugs and vitamins at advanced age. Int J Vit Nutr Res 69: 173–178, 1999

    Google Scholar 

  173. Jacobs EJ, Connell CJ, McCullough ML, Chao A, Jonas CR, Rodriguez C, Calle EE, Thun MJ: Vitamin C, vitamin E, and multivitamin supplement use and stomach cancer mortality in the cancer prevention study II cohort. Cancer Epidemiol Biomarkers Prev 11: 35–41, 2002

    Google Scholar 

  174. Collins AR, Gedik CM, Olmedilla B, Southon S, Bellizzi M: Oxidative DNA damage measured in human lymphocytes: Large differences between sexes and between countries, and correlations with heart disease mortality rates. FASEB J 12: 1397–1400, 1998

    Google Scholar 

  175. Jacob RA: The integrated antioxidant system. Nutr Res 15: 755–766, 1995

    Google Scholar 

  176. Lee SH, Oe T, Blair IA: Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins. Science 292: 2083–2086, 2001

    Google Scholar 

  177. Halliwell B: Vitamin C: Antioxidant or pro-oxidant in vivo? Free Rad Res 25: 439–454, 1996

    Google Scholar 

  178. Buettner GR: The pecking order of free-radicals and antioxidants — Lipid-peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys 300: 535–543, 1993

    Google Scholar 

  179. Kelley EE, Buettner GR, Burns CP: Relative alpha-tocopherol deficiency in cultured-cells — Free radical-mediated lipid-peroxidation, lipid oxidizability, and cellular polyunsaturated fatty-acid content. Arch Biochem Biophys 319: 102–109, 1995

    Google Scholar 

  180. IUPAC Commission on Nomenclature of Organic Chemistry, 1976, Rules for the nomenclature of organic chemistry. Section E: Stereochemistry, Recommendations. Pure Appl Chem 45: 11–30, 1974

    Google Scholar 

  181. Van Acker SA, Koymans LM, Bast A: Molecular pharmacology of vitamin E: Structural aspects of antioxidant activity. Free Rad Biol Med 15: 311–328, 1993

    Google Scholar 

  182. Richter C: Biophysical consequences of lipid peroxidation in membranes. Chem Phys Lipids 44: 175–189, 1987

    Google Scholar 

  183. Gutteridge JM: Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41: 1819–1828, 1995

    Google Scholar 

  184. Davies KJA: Oxidative stress: The paradox of aerobic life. Biochem Soc Symp 61: 1–31, 1996

    Google Scholar 

  185. Jacobs EJ, Connell CJ, McCullough ML, Chao A, Jonas CR, Rodriguez C, Calle EE, Thun MJ: Vitamin C, vitamin E, and multivitamin supplement use and stomach cancer mortality in the cancer prevention study II cohort. Cancer Epidemiol Biomark Prev 11: 35–41, 2002

    Google Scholar 

  186. ATBC trial. Cigarette Smoke or Alcohol Consumption May Enhance Adverse Effects of Beta Carotene in Vitamin Prevention Trials. National Institute of Health, National Cancer Institute, 1996

  187. Edge R, McGarvey DJ, Truscott TG: The carotenoids as anti-oxidants — A review. J Photochem Photobiol B Biol 41: 189–200, 1997

    Google Scholar 

  188. Torun M, Yardim S, Gonenc A, Sargin H, Menevse A, Simsek B: Serum beta-carotene, vitamin-e, vitamin-c and malondialdehyde levels in several types of cancer. J Clin Pharm Therap 20: 259–263, 1995

    Google Scholar 

  189. van Lieshout M, West CE, van Breemen RB: Isotopic tracer techniques for studying the bioavailability and bioefficacy of dietary carotenoids, particularly beta-carotene, in humans: A review. Am J Clinic Nutr 77: 12–28, 2003

    Google Scholar 

  190. Burton GW, Ingold KU: Beta-carotene — An unusual type of lipid antioxidant. Science 224: 569–573, 1984

    Google Scholar 

  191. Rice-Evans CA, Sampson J, Bramley PM, Holloway DE: Why do we expect carotenoids to be antioxidants in vivo? Free Rad Res 26: 381–398, 1997

    Google Scholar 

  192. Wang XD, Russell RM: Procarcinogenic and anticarcinogenic effects of beta-carotene. Nutr Rev 57: 263–272, 1999.

    Google Scholar 

  193. CARET Trial: Cigarette Smoke or Alcohol Consumption May Enhance Adverse Effects of Beta Carotene in Vitamin Prevention Trials. National Institute of Health, National Cancer Institute, 1996

  194. Polyakov NE, Konovalov VV, Leshina TV, Luzina OA, Nalakhutdinov NF, Konovalova TA, Kispert LD: One-electron transfer product of quinone addition to carotenoids EPR and optical absorption studies. J Photochem Photobiol A Chem 141: 117–126, 2001

    Google Scholar 

  195. Gao YL, Konovalova TA, Lawrence JN, Smitha MA, Nunley J, Schad R, Kispert LD: Interaction of carotenoids and Cu2+ in Cu-MCM-41: Distance-dependent reversible electron transfer. J Phys Chem B 107: 2459–2465, 2003

    Google Scholar 

  196. Polyakov NE, Leshina TV, Konovalova TA, Kispert LD: Carotenoids as scavengers of free radicals in a Fenton reaction: Antioxidants or pro-oxidants? Free Rad Biol Med 31: 398–404, 2001

    Google Scholar 

  197. El-Agamey A, McGarvey DJ: Evidence for a lack of reactivity of carotenoid addition radicals towards oxygen: A laser flash photolysis study of the reactions of carotenoids with acylperoxyl radicals in polar and non-polar solvents. J Am Chem Soc 125: 3330–3340, 2003

    Google Scholar 

  198. Rietjens IMCM, Boersma MG, de Haan L, Spenkelink B, Awad B, Cnubben NHP, van Zanden JJ, van der Woude H, Alink GM, Koeman JH: The pro-oxidant chemistry of the natural antioxidants vitamin C, vitamin E, carotenoids and flavonoids. Environ Toxicol Pharmacol 11: 321–333, 2002

    Google Scholar 

  199. Young AJ, Lowe GM: Antioxidant and prooxidant properties of carotenoids. Arch Biochem Biophys 385: 20–27, 2001

    Google Scholar 

  200. Woods JA, Bilton RF, Young AJ: Beta-Carotene enhances hydrogen peroxide-induced DNAdamage in human hepatocellular HepG2 Cells. FEBS Lett 449: 255–258, 1999

    Google Scholar 

  201. Farombi EO, Britton G: Antioxidant activity of palm oil carotenes in peroxyl radical-mediated peroxidation of phosphatidyl choline liposomes. EDOX REPORT 4: 61–68

  202. Kennedy TA, Liebler DE: Peroxyl radical oxidation of beta-carotene — Formation of beta-carotene epoxides. Chem Res Toxicol 4: 290–295, 1991

    Google Scholar 

  203. Kennedy TA, Liebler DE: Peroxyl radical scavenging by beta-carotene in lipid bilayers — Effect of oxygen partial-pressure. J Biol Chem 267: 4658–4663, 1992

    Google Scholar 

  204. Mortensen A, Skibsted LH, Sampson J, RiceEvans C, Everett SA: Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants. FEBS Lett 418: 91–97, 1997

    Google Scholar 

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Authors and Affiliations

  1. Faculty of Chemical and Food Technology, Slovak Technical University, SK-812 37, Bratislava, Slovakia.

    Marian Valko, Mario Izakovic & Milan Mazur

  2. School of Chemistry, University of Reading, Reading, UK

    Christopher J. Rhodes

  3. Chemistry Program, Roosevelt University, Chicago, IL, USA

    Joshua Telser

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Valko, M., Izakovic, M., Mazur, M. et al. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem 266, 37–56 (2004). https://doi.org/10.1023/B:MCBI.0000049134.69131.89

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