Abstract
In living cells reactive oxygen species (ROS) are formed continuously as a consequence of metabolic and other biochemical reactions as well as external factors. Some ROS have important physiological functions. Thus, antioxidant defense systems cannot provide complete protection from noxious effects of ROS. These include oxidative damage to DNA, which experimental studies in animals and in vitro have suggested are an important factor in carcinogenesis. Despite extensive repair oxidatively modified DNA is abundant in human tissues, in particular in tumors, i.e., in terms of 1–200 modified nucleosides per 105 intact nucleosides. The damaged nucleosides accumulate with age in both nuclear and mitochondrial DNA. The products of repair of these lesions are excreted into the urine in amounts corresponding to a damage rate of up to 104 modifications in each cell every day. The most abundant of these lesions, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), is also the most mutagenic, resulting in GT transversions which are frequently found in tumor relevant genes. A series of other oxidative modifications of base and sugar residues occur frequently in DNA, but they are less well studied and their biological significance less apparent. The biomarkers for study of oxidative DNA damage in humans include urinary excretion of oxidized nucleosides and bases as repair products and modifications in DNA isolated from target tissue or surrogate cells, such as lymphocytes. These biomarkers reflect the rate of damage and the balance between the damage and repair rate, respectively. By means of biomarkers a number of important factors have been studied in humans. Ionizing radiation, a carcinogenic and pure source of ROS, induced both urinary and leukocyte biomarkers of oxidative DNA damage. Tobacco smoking, another carcinogenic source of ROS, increased the oxidative DNA damage rate by 35–50% estimated from the urinary excretion of 8-oxodG, and the level of 8-oxodG in leukocytes by 20–50%. The main endogenous source of ROS, the oxygen consumption, showed a close correlation with the 8-oxodG excretion rate although moderate exercise appeared to have no immediate effect. So far, cross-sectional study of diet composition and intervention studies, including energy restriction and antioxidant supplements, have generally failed to show an influence on the oxidative DNA modification. However, a diet rich of Brussels sprouts reduced the oxidative DNA damage rate, estimated by the urinary excretion of 8-oxodG, and the intake of vitamin C was a determinant for the level of 8-oxodG in sperm DNA. A low-fat diet reduced another marker of oxidative DNA damage in leukocytes. In patients with diseases associated with a mechanistically based increased risk of cancer, including Fanconi anemia, chronic hepatitis, cystic fibrosis, and various autoimmune diseases, the biomarker studies indicate an increased rate of oxidative DNA damage or in some instances deficient repair. Human studies support the experimentally based notion of oxidative DNA damage as an important mutagenic and apparently carcinogenic factor. However, the proof of a causal relationship in humans is still lacking. This could possibly be supported by demonstration of the rate of oxidative DNA damage as an independent risk factor for cancer in a prospective study of biobank material using a nested case control design. In addition, oxidative damage may be important for the aging process, particularly with respect to mitochondrial DNA and the pathogenesis of inflammatory diseases.
Similar content being viewed by others
Abbreviations
- EC :
-
Electrochemical detection
- ELISA :
-
Enzyme linked immunosorbent assay
- GC/MS:
-
Gas chromatography — mass spectrometry
- HPLC :
-
High-performance liquid chromatography
- 8-oxodG :
-
8-Oxo-7,8-dihydro-2′-deoxyguanosine
- RA :
-
Rheumatoid arthritis
- ROS :
-
Reactive oxygen species
- SIM :
-
Selective ion monitoring
- SLE :
-
Systemic lupus erythematosus
- dTg :
-
Thymidine glycol
- Tg :
-
Thymine glycol
References
Spector A, William HG (1981) Hydrogen peroxide and human cataract. Exp Eye Res 33:673–681
Ames BN (1989) Endogenous oxidative DNA damage, aging, and cancer. Free Radic Res Commun 7:121–128
Fraga C, Shigenaga MK, Park J-W, Degan P, Ames BN (1990) Oxidative damage to DNA during aging: 8-hydroxy-2′-deoxyguanosine in rat organ DNA and urine. Proc Natl Acad Sci USA 87:4533–4537
Lunec J (1990) Free radicals: their involvement in disease processes. Ann Clin Biochem 27:173–182
Reilly PM, Schiller HJ, Bulkley GB (1991) Pharmacologic approach to tissue injury mediated be free radicals and other reactive oxygen metabolites. Am J Surg 161:488–503
Greenwald RA (1991) Oxygen radicals, inflammation, and arthritis: pathophysiological considerations and implications for treatment. Semin Arthritis Rheum 20:219–240
Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90:7915–7922
Ames BN, Gold LS, Willett WC (1995) The causes and prevention of cancer. Proc Natl Acad Sci USA 92:5258–5265
Clayson DB, Mehta R, Iverson F (1994) Oxidative DNA damage — the effects of certain genotoxic and operationally non-genotoxic carcinogens. Mutation Res 317:25–42
Cerutti P, Ghosh R, Oya Y, Amstad P (1994) The role of the cellular antioxidant defense in oxidant carcinogenesis. Environ Health Perspect 102 Suppl 10:123–129
Cerutti P, Shah G, Peskin A, Amstad P (1992) Oxidant carcinogenesis and antioxidant defense. Ann N Y Acad Sci 663:158–166
Ames BN, Shigenaga MK, Gold LS (1993) DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis. Environ Health Perspec 101 [Suppl 5]:35–44
Block G, Patterson B, Subar A (1992) Fruit, vegetables, and cancer prevention: a review of the epidemilogical evidence. Nutr Cancer 18:1–29
Block G (1992) The data support a role for antioxidants in reducing cancer risk. Nutr Rev 50:207–213
The Alpha-Tocopherol, Beta Carotene Cancer Prevention Group (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330:1029–1035
Smigel K, Edmonds S (1996) Beta carotene and vitamin A halted in lung cancer prevention trial. CancerNet News. Natl Cancer Inst
Omenn GS, Goodman GE, Thornquist MD, Rosenstock L, Barnhart S, Gylys-Colwell I, Metch B, Lund B (1993) The Carotene and Retinol Efficacy Trial (CARET) to prevent lung cancer in high-risk populations: pilot study with asbestos-exposed workers. Cancer Epidemiol Biomarkers Prev 2:381–387
Greenberg ER, Baron JA, Tosteson TD, Freeman DH, Beck GJ, Bond JH, Colacchio TA, Coller JA, Frankl HD, Haile RW, Mandel JS, Nierenberg DW, Rothstein R, Snover DC, Stevens MM, Summers RW, van Stolk RU (1994) A clinical trial of antioxidant vitamins to prevent colorectal adenoma. N Engl J Med 331:141–147
Blot WJ, Li JY, Taylor PR, Guo W, Dawsey S, Wang GQ, Yang CS, Zheng SF, Gail M, Li GY, et al. (1993) Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 85:1483–1492
Halliwell B, Gutteridge JMC (1989) Free radicals in biology and medicine. Clarendon, Oxford 2:1–543
Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause or consequence. Lancet 344:721–724
Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605
Frei B, Forte TM, Ames BN, Cross CE (1991) Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Biochem J 277:133–138
Nagashima M, Kasai H, Yokota J, Nagamachi Y, Ichinose T, Sagai M (1995) Formation of an oxidative DNA damage, 8-hydroxydeoxyguanosine, in mouse lung DNA after intratracheal instillation of diesel exhaust particles and effects of high dietary fat and beta-carotene on this process. Carcinogenesis 16:1441–1445
Kolachana P, Subrahmanyam VV, Meyer KB, Zhang L, Smith MT (1993) Benzene and its phenolic metabolites produce oxidative DNA damage in HL60 cells in vitro and in the bone marrow in vivo. Cancer Res 53:1023–1026
Shen HM, Ong CN, Lee BL, Shi CY (1995) Aflatoxin B 1-induced 8-hydroxydeoxyguanosine formation in rat hepatic DNA. Carcinogenesis 16:419–22
Mauthe RJ, Cook VM, Coffing SL, Baird WM (1995) Exposure of mammalian cell cultures to benzo[a]pyrene and light results in oxidative DNA damage as measured by 8-hydroxydeoxyguanosine formation. Carcinogenesis 16:133–137
Sussman MS, Bulkley GB (1990) Oxygen-derived free radicals in reperfusion injury. Meth Enzymol 186:711–723
Zimmerman BJ, Granger DN (1992) Reperfusion injury. Surg Clin North Am 72:65–83
Moncada S, Higgs A (1993) The l-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012
deRojas-Walker T, Tamir S, Ji H, Wishnok JS, Tannenbaum SR (1995) Nitric oxide induces oxidative damage in addition to deamination in macrophage DNA. Chem Res Toxicol 8:473–477
Davies KJA (1987) Protein damage and degradation by oxygen radicals. J Biol Chem 262:9895–9901
Epe B (1991) Genotoxicity of singlet oxygen. Chem-Biol Interact 80:239–260
Feig DI, Reid TM, Loeb LA (1994) Reactive oxygen species in tumorigenesis. Cancer Res suppl. 54:1890s-1894s
Dizdaroglu M (1991) Chemical determination of free radicalinduced damage to DNA. Free Radic Biol Med 10:225–242
Dizdaroglu M (1994) Chemical determination of oxidative DNA damage by gas chromatography-mass spectrometry. Meth Enzymol 234:3–16
Breen AP, Murphy A (1995) Reactions of oxyl radical with DNA. Free Radic Biol Med 18:1033–1077
Shigenaga MK, Gimeno CJ, Ames BN (1989) Urinary 8-hydroxy-2′-deoxyguanosine as a biological marker of in vivo oxidative DNA damage. Proc Natl Acad Sci USA 86:9697–9701
Floyd RA, Watson JJ, Wong PK, Altmiller DH, Rickard RC (1986) Hydroxyl free radical adduct of deoxyguanosine: sensitive detection and mechanisms of formation. Free Radic Res Commun 1:163–172
Floyd RA (1990) The role of 8-hydroxyguanine in carcinogenesis. Carcinogenesis 11:1447–1450
Fischer-Nielsen A, Jeding IB, Loft S (1994) Radiation induced formation of 8-hydroxy-2'deoxyguanosine and its prevention by scavengers. Carcinogenesis 15:1609–1612
Ramotar D, Demple B (1993) Enzymes that repair oxidative damage to DNA. In: Halliwell B, Aruoma OI (eds) DNA and free radicals. Horwood, Chichester
Bemple B, Harrison L (1994) Repair of oxidative damage to DNA: enzymology and biology. Annu Rev Biochem 63:915–948
Boiteux S, Gajewski E, Lavai J, Dizdaroglu M (1992) Substrate specificity of the Escherischia coli Fpg protein (formamidopyrimidine-DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization. Biochemistry 31:106–110
Bohr VA, Taffe BG, Larminat F (1995) DNA repair, oxidative stress and aging. In: Cutler RG, Packer L, Bertram J, Mori A (eds) Oxidative stress and aging. Birkhauser, Basel
Bessho T, Tano K, Kasai H, Ohtsuka E, Nishimura S (1993) Evidence for two DNA repair enzymes for 8-hydroxyguanine (7,8-dihydro-guanine) in human cells. J Biol Chem 268:19416–19421
Czeczot H, Tudek B, Lambeert B, Laval J, Boiteux S (1991) Escherischia coli fpg protein and UvrABC endonuclease repair DNA damage induced by methylene blue plus visible light in vivo and in vitro. J Bacteriol 173:3419–3424
Shibutani S, Takeshita M, Grollman AP (1991) Insertion of specific bases during DNA synthesis past the oxidation damaged base 8-oxodG. Nature 349:431–434
Kamiya H, Miura K, Ishikawa H, Nishimura S, Ohtsuka E (1992) c-Ha-ras containing 8-hydroxyguanine at codon 12 induces point mutations at the modified and adjacent positions. Cancer Res 52:3483–3485
Mo JY, Maki H, Sekiguchi M (1992) Hydrolytic elimination of a mutagenic nucleotide, 8-oxodGTP, by human 18-kilodalton protein: sanitization of nucleotide pool. Proc Natl Acad Sci USA 89:11021–11025
Sakumi K, Furuichi M, Tsuzuki T, Kakuman T, Kawabata S, Maki H, Sekiguchi M (1993) Cloning and expression of a cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis. J Biol Chem 268:23524–23530
Furuichi M, Yoshida MC, Oda H, Tajiri T, Nakabeppu Y, Tsuzuki T, Sekiguchi M (1994) Genomic structure and chromosome location of the human mutT homologue gene MTH1 encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion. Genomics 24:485–490
Wani G, D'Ambrosia SM (1995) Cell type-specific expression of human 8-oxo-7,8-dihydroguanosine triphosphatase in normal breast and skin tissues in vivo. Carcinogenesis 16:277–283
Tajiri T, Maki H, Sekiguchi M (1995) Functional cooperation of MutT, MutM and MutY proteins in preventing mutations caused by spontaneous oxidation of guanine nucleotide in Escherichia coli. Mutation Res 336:257–267
Digweed M (1993) Human genetic instability syndromes: single gene defects with increased risk of cancer. Toxicol Lett 67:259–281
Hansson J (1992) Inherited defects in DNA repair and susceptibility to DNA-damaging agents. Toxicol Lett 64–65:141–148
Retèl J, Hoebee B, Braun JEF, Lutgerink JT, van den Akker E, Wanamarta AH, Joneje H, Lafleur MVM (1993) Mutational specificity of oxidative DNA damage. Mutation Res 299:165–182
McBride TJ, Schneider JE, Floyd RA, Loeb LA (1992) Mutations induced by methylene blue plus light in single-stranded M13mp2. Proc Natl Acad Sci USA 89:6866–6870
Emmert S, Epe B, Saha-Moller CR, Adam W, Runger TM (1995) Assessment of genotoxicity and mutagenicity of 1,2-dioxetanes in human cells using a plasmid shuttle vector. Photochem Photobiol 61:136–141
Kuchino Y, Mori F, Kasai H, Inoue H, Iwai S, Miura K, Ohtsuka E, Nishimura S (1987) Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues. Nature 327:77–79
Kamiya H, Murata-Kamiya N, Fujimuro M, Kido K, Inoue H, Nishimura S, Masutani C, Hanaoka F, Ohtsuka E (1995) Comparison of incorporation and extension of nucleotides in vitro opposite 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) in hot spots of the c-Ha-ras gene. Jpn J Cancer Res 86:270–276
Shibutani (1993) Quantitation of base substitutions and deletions induced by chemical mutagens during DNA synthesis in vitro. Chem Res Toxicol 6:625–629
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
Higinbotham KG, Rice JM, Divan BA, Kasprzak KS, Reed CD, Perantoni AO (1992) GGT to GTT transversion in codon 12 of the K-ras oncogene in rat renal sarcomas induced with nickel subsulfide or nickel subsulfiede/iron are consistent with oxidative damage to DNA. Cancer Res 52:4747–4751
Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–52
Harris CC, Hollstein M (1993) Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 329:1318–1327
Hussain SP, Aguilar F, Amstad P, Cerutti P (1994) Oxy-radical induced mutagenesis of hotspot codons 248 and 249 of the human p53 gene. Oncogene 9:2277–2281
Feig DI, Loeb LA (1993) Mechanisms of mutation by oxidative DNA damage: reduced fidelity of mammalian DNA polymerase. Biochemistry 32:4466–4473
Weitzman SA, Turk PW, Milkowaki DH, Kozlowski K (1994) Free radical adducts induce alterations in DNA cytosine methylation. Proc Natl Acad Sci USA 91:1261–1264
Olinski R, Zastawny T, Budzbon J, Skokowski J, Zegarski W, Dizdaroglu M (1992) DNA base modification in chromatin of human cancerous tissues. FEBS Lett 309:193–198
Bartsch H, Petruzelli S, De Flora S, Hietanen E, Camus A-M, Castegnaro M, Geneste O, Camoirano A, Saracci R, Giuntini C (1991) Carcinogen metabolism and DNA adducts in human lung tissues as affected by tobacco smoking or metabolic phenotype: a case-control study on lung cancer. Mutation Res 250:103–114
Cathcart R, Schwiers E, Saul RL, Ames BN (1984) Thymine glycol and thymidine glycol in human and rat urine: a possible assay for oxidative DNA damage. Proc Natl Acad Sci USA 81:5633–5637
Adelman R, Saul RL, Ames BN (1988) Oxidative damage to DNA: relation to species metabolic rate and life span. Proc Natl Acad Sci USA 85:2706–2708
Loft S, Vistisen K, Ewertz M, Tjønneland A, Overvad K, Poulsen HE (1992) Oxidative DNA-damage estimated by 8-hydroxydeoxyguanosine excretion in man: influence of smoking, gender and body mass index. Carcinogenesis 13:2241–2247
Wang YJ, Ho YS, Lo MJ, Lin JK (1995) Oxidative modification of DNA bases in rat liver and lung during chemical carcinogenesis and aging. Chem-Biol Interact 94:135–145
Ogawa T, Higashi S, Kawarada Y, Mizumoto R (1995) Role of reactive oxygen in synthetic estrogen induction of hepatocellular carcinomas in rats and preventive effect of vitamins. Carcinogenesis 16:831–836
Hayakawa M, Hattori K, Sugiyama S, Ozawa T (1992) Ageassociated oxygen damage and mutations in mitochondrial DNA in human hearts. Biochem Biophys Res Commun 189:979–985
Mecocci P, MacGarvey U, Kaufman AE, Koontz D, Shoffner JM, Wallace DC, Beal MF (1993) Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol 34:609–616
Bashir S, Harris G, Denman MA, Blake DR, Winyard PG (1993) Oxidative DNA damage and cellular sensitivity to oxidative stress in human autoimmune diseases. Ann Rheum Dis 52:659–666
Frenkel K, Zhong Z, Wei H, Karkokoszka J, Patel U, Rashid K, Georgescu M, Solomon JJ (1991) Quantitative high-performance liquid chromatography analysis of DNA oxidized in vitro and in vivo. Anal Biochem 196:126–136
Cadet J, Weinfeld M (1993) Detecting DNA damage. Anal Biochem 65:675A-682A
Povey AC, Wilson VL, Weston A, Doan VT, Wood ML, Essigmann JM, Shields PG (1993) Detection of oxidative damage by 32P-postlabelling: 8-hydroxydeoxyguanosine as a marker of exposure. In: Phillips DH, Castegnaro M, Bartsch H (eds) Postlabelling methods for detection of DNA adducts. IARC, Lyon
Cajigas A, Gayer M, Beam C, Steinberg JJ (1994) Ozonation of DNA forms adducts: a 32P-DNA labelling and thin layer chromatography technique to measure DNA environmental biomarkers. Arch Environ Health 49:25–36
Musarrat J, Wani AA (1994) Qunatitative immunoanalysis of promutagenic 8-hydroxy-2′-deoxyguanosine in oxidized DNA. Carcinogenesis 15:2037–2043
Yin B, Whyatt RM, Perera FP, Randall MC, Cooper TB, Santella RM (1995) Determination of 8-hydroxydeoxyguanosine by an immunoaffinity chromatography-monoclonal antibody-based ELISA. Free Radic Biol Med 18:1023–1032
Halliwell B, Dizdaroglu M (1992) The measurement of oxidative damage to DNA by HPLC and GC/MS techniques. Free Radic Res Commun 16:75–87
Lunec J, Herbert K, Blount S, Griffiths HR, Emery P (1994) 8-Hydroxydeoxyguanosine. A marker of oxidative DNA damage in systemic lupus erythematosus. FEBS Lett 348:131–138
Teixeira AJ, Ferreira MR, van Dijk WJ, van de Werken G, de Jong AP (1995) Analysis of 8-hydroxy-2′-deoxyguanosine in rat urine and liver DNA by stable isotope dilution gas chromatography/mass spectrometry. Anal Biochem 226:307–319
Ravanat J-L, Turesky RJ, Gremaud E, Trudel LJ, Stader RH (1995) Determination of 8-oxoguanine in DNA by gas chromatography-mass spectrometry and HPLC-electrochemical detection: overestimation of the background level of the oxidized base by the gas chromatography-mass spectrometry assay. Chem Res Toxicol (in press)
Hamberg M, Zhang LY (1995) Quantitative determination of 8-hydroxyguanine and guanine by isotope dilution masss spectrometry. Anal Biochem 229:336–344
Claycamp HG (1992) Phenol sensitization of DNA to subsequent oxidative damage in 8-hydroxyguanine assays. Carcinogenesis 13:1289–1292
Adachi S, Zeisig M, Moller L (1995) Improvements in the analytical method for 8-hydroxydeoxyguanosine in nuclear DNA. Carcinogenesis 16:253–258
Takeuchi T, Nakajima M, Ohta Y, Mure K, Takeshita T, Morimot K (1994) Evaluation of 8-hydroxydeoxyguanosine, a typical oxidative DNA damage, in human leukocytes. Carcinogenesis 15:1519–1523
Degan P, Bonassi S, De Caterina M, Korkina LG, Pinto L, Scopacasa F, Zatterale A, Calzone R, Pagano G (1995) In vivo accumulation of 8-hydroxy-2′-deoxyguanosine in DNA correlates with release of reactive oxygen species in Fanconi's anaemia families. Carcinogenesis 16:735–741
Epe B, Pflaum M, Haring M, Hegler J, Rudiger H (1993) Use of repair endonucleases to characterize DNA damage induced by reactive oxygen species in cellular and cell-free systems. Toxicol Lett 67:57–72
Gedik CM, Ewen SW, Collins AR (1992) Single-cell gel electrophoresis applied to the analysis of UV-C damage and its repair in human cells. Inter J Rad Biol 62:313–320
McKelvey-Martin VJ, Green MH, Schmezer P, Pool-Zobel BL, De Meo MP, Collins A (1993) The single cell gel electrophoresis assay (comet assay): a European review. Mutation Res 288:47–63
Epe B (1995) DNA damage profiles induced by oxidizing agents. Rev Physiol Biochem Pharmacol 127:223–249
Collins AR, Ai-guo M, Duthie SJ (1995) The kinetics of repair of oxidative DNA damage (strand breaks and oxidised pyrimidines) in human cells. Mutation Res 336:69–77
Loft S, Larsen PN, Rasmussen A, Fischer-Nielsen A, Bondesen S, Kirkegaard P, Rasmussen LS, Ejlersen E, Tornøe K, Bergholdt R, Poulsen HE (1995) Oxidative DNA damage after transplantation of the liver and small intestine in pigs. Transplantation 59:16–20
Faure H, Incardona MF, Boujet C, Cadet J, Ducros V, Favier A (1993) Gas chromatographic-mass spectrometric determination of 5-hydroxymethyluracil in human urine by stable isotope dilution. J Chromatogr 616:1–7
Suzuki J, Inoue Y, Suzuki S (1995) Changes in urinary level of 8-hydroxyguanine by exposure to reactive oxygengenerating substances. Free Radic Biol Med 18:431–436
Simic MG, Bergtold DS (1991) Dietary modulation of DNA damage in human. Mutation Res 250:17–24
Tagesson C, Källberg M, Leanderson P (1992) Determination of urinary 8-hydroxydeoxyguanosine by coupled-column high-perfomance liquid chromatography with electrochemical detection: a noninvasive assay for in vivo oxidative DNA damage in humans. Toxicol Meth 1:242–251
Park E-M, Shigenaga MK, Degan P, Korn T, Kitzler JW, Wehr CM, Kolachana P, Ames BN (1992) Assay of excised oxidative DNA lesions: isolation of 8-oxoguanine and its nucleoside derivatives from biological fluids with a monoclonal antibody column. Proc Natl Acad Sci USA 89:3375–3379
Shigenaga MK, Aboujaoude EN, Chen Q, Ames BN (1994) Assays of oxidative DNA damage biomarkers 8-oxo-2′-deoxyguanosine and 8-oxoguanine in nuclear DNA and biological fluids by high-performance liquid chromatography with electrochemical detection. Meth Enzymol 234:16–33
Tagesson C, Kallberg M, Klintenberg C, Starkhammar H (1995) Determination of urinary 8-hydroxydeoxyguanosine by automated coupled-column high performance liquid chromatography: a powerful technique for assaying in vivo oxidative DNA damage in cancer patients. Eur J Cancer 31A:934–940
Osawa T, Yoshida A, Kawakishi S, Yamashita K, Ochi H (1995) Protective role of dietary antioxidants in oxidative stress. In: Cutler RG, Packer L, Bertram J, Mori A (eds) Oxidative stress and aging. Birkhauser, Basel
Prieme H, Loft S, Cutler RG, Poulsen HE (1995) Measurement of oxidative DNA injury in humans: evaluation of a comercially available ELISA assay. In: International Conference on Natural Antioxidants and Lipid Peroxidation in Atherosclerosis and Cancer. (in press)
Klein JC, Bleeker MJ, Saris CP, Roelen HCPF, Brugghe HF, van den Elst H, van der Marel GA, van Boom JH, Westra JG, Kriek E, Berns AJM (1992) Repair and replication of plasmids with site-specific 8-oxodG and 8-AAFdG residues in normal and repair-deficient human cells. Nucleic Acids Res 20:4437–4443
Hayakawa H, Taketomi A, Sakumi K, Kuwano M, Sekiguchi M (1995) Generation and elimination of 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate, a mutagenic substrate for DNA synthesis, in human cells. Biochemistry 34:89–95
Witt EH, Reznick AZ, Viguie CA, Starke-Reed P, Packer L (1992) Exercise, oxidative damage and effects of antioxidant manipulation. J Nutr 122:766–773
Loft S, Wierik EJMV, van der Berg H, Poulsen HE (1995) Energy restriction and oxidative DNA damage. Cancer Epidemiol Biomarkers Prev 4:515–519
Bergtold DS, Berg CD, Simic MG (1990) Urinary biomarkers in radiation therapy of cancer. Adv Exp Med Biol 264:311–316
Blount S, Griffiths HR, Lunec J (1991) Reactive oxygen species damage to DNA and its role in systemic lupus erythematosus. Mol Aspects Med 12:93–105
Kasai H, Crain PF, Kuchino Y, Nishimura S, Ootsuyama A, Tanooka H (1986) Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair. Carcinogenesis 7:1849–1851
Kiyosawa H, Suko M, Okudaira H, Murata K, Miyamoto T, Chung MH, Kasai H, Nishimura S (1990) Cigarette smokeing induces formation of 8-hydroxydeoxyguanosine, one of the oxidative DNA damages in human peripheral leucocytes. Free Radic Res Commun 11:23–27
Lagorio S, Tagesson C, Forastiere F, Axelson O, Carere A (1994) Exposure to benzene and urinary concentrations of 8-hydroxydeoxyguanosine, a biological marker of oxidative damage to DNA. Occup Environ Med 51:739–743
Wilson VL, Taffe BG, Shields PG, Powey AC, Harris CC (1993) Detection and quantification of 8-hydroxydeoxyguanosine addducts in peripheral blood of people exposed to ioonizing radiation. Environ Health Perspec 99:261–263
Loft S, Astrup A, Buemann B, Poulsen HE (1994) Oxidative DNA damage correlates with oxygen consumption in humans. FASEB J 8:534–537
Cutler RG (1991) Human longevity and aging: possible role of reactive oxygen species. Ann N Y Acad Sci 621:1–28
Loft S, Fischer-Nielsen A, Jeding IB, Vistisen K, Poulsen HE (1993) 8-Hydroxydeoxyguanosine as a biomarker of oxidative DNA damage. J Toxicol Environ Health 40:391–404
Sohal RS, Orr WC (1992) Relationship between antioxidants, prooxidants, and the aging process. Ann N Y Acad Sci 663:74–84
Else PL, Hulbert AJ (1985) Mammals: an allometric study of metabolism at tissue and mitochondrial level. Am J Physiol 248:R415-R421
Richter C, Park J-W, Ames BN (1988) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci USA 85:6465–6467
Richter C (1995) Oxidative damage to mitochondrial DNA and its relationship to ageing. Int J Biochem Cell Biol 27:647–653
Haramaki N, Packer L (1994) Oxidative stress indices in exercise. In: Sen CK, Packer L, Hänninen O (eds) Exercise and oxygen toxicity. Elsevier, Amsterdam
Inoue T, Mu Z, Sumikawa K, Adachi K, Okochi T (1993) Effect of physical exercise on the content of 8-hydroxydeoxyguanosine in nuclear DNA prepared from human lymphocytes. Jpn J Cancer Res 84:720–725
Nielsen HB, Hanel B, Loft S, Poulsen HE, Pedersen BK, Diamant M, Vistisen K, Secher NH (1995) Restricted pulmonary diffusion capacity after exercise is not an ARDS-like injury. J Sport Sci 13:109–113
Alessio HM (1993) Exercise-induced oxidative stress. Med Sci Sports Exerc 25:218–224
Poulsen HE, Loft S, Vistisen K (1995) Increased oxidative DNA damage after 30 days of vigorous exercise. J Sport Sci (in press)
Weindruch R, Albanes D, Kritchevsky D (1991) The role of calories and caloric restriction in carcinogenesis. Hematol Oncol Clin North Am 5:79–89
Masoro EJ, Shimokawa I, Yu BP (1991) Retardation of the aging processes in rats by food restriction. Ann N Y Acad Sci 621:337–352
Turturro A, Hart RW (1991) Longevity-assurance meachanism in caloric restriction. Ann N Y Acad Sci 621:363–372
Weraarchakull N, Strong R, Wood G, Richardson A (1989) The effect of aging and energy restriction on DNA repair. Exp Cell Res 181:197–204
Chung MH, Kasai H, Nishimura S, Yu BP (1992) Protection of DNA damage by dietary restriction. Free Radic Biol Med 12:523–525
Djuric Z, Lu MH, Lewis SM, Luongo DA, Chen XW, Heilbrun LK, Reading BA, Duffy PH, Hart RW (1992) Oxidative DNA damage levels in rats fed low-fat, high-fat or calorie-restricted diets. Toxicol Appl Pharmacol 115:156–160
Semsei I, Rao G, Richardson A (1989) Changes in the expression of Superoxide dismutase and catalase as a function of age and dietary restriction. Biochem Biophys Res Commun 164:620–625
Youngman LD, Park J-YK, Ames BN (1992) Protein oxidation associated with aging is reduced by dietary restriction of proetin or calories. Proc Natl Acad Sci USA 89:9112–9116
Wieric EJMV, Leeuwen REW van, Hendriks HFJ, Verhagen H, Loft H, Poulsen HE, Berg H van der (1995) Moderate energy restriction does not affect parameters of oxidative stress and genotoxicity in man. J Nutr 125:2631–2639
Djuric Z, Heilbrun LK, Reading BA, Boomer A, Valeriote FA, Martino S (1991) Effects of low-fat diet on levels of oxidative damage to DNA in human peripheral nucleated blood cells. J Natl Cancer Inst 83:766–769
Leanderson P, Tagesson C (1990) Cigarette smoke-induced DNA-damage: role of hydroquinone and catechol in the formation of the oxidative DNA-adduct, 8-hydroxydeoxyguanosine. Chem-Biol Interact 75:71–81
Leanderson P, Tagesson C (1992) Cigarette smoke-induced DNA damage in cultured human lung cells: role of hydroxyl radicals and enduclease activation. Chem-Biol Interact 810:197–208
Ziegler RG (1989) A review of the epidemiologic evidence that carotenoids reduce the risk of cancer. J Nutr 119:116–122
Riemersma RA, Wood DA, Macintyre CCA, Elton RA, Gey KF, Oliver MF (1991) Risk of angina pectoris and plasma concentration of vitamin A, C, and E and carotene. Lancet 337:1–5
Adachi S, Yoshida S, Kawamura K, Takahashi M, Uchida H, Odagiri Y, Takemoto K (1994) Inductions of oxidative DNA damage and mesothelioma by crocidolite, with special reference to the presence of iron inside and outside of asbestos fiber. Carcinogenesis 15:753–758
Hanaoka T, Tsugane S, Yamano Y, Takahashi T, Kasai H, Natori Y, Watanabe S (1993) Quantitative analysis of 8-hydroxyguanine in peripheral blood cells: an application for asbestosis patients. Int Arch Occup Environ Health 65:S215-S217
Tagesson C, Chabiuk D, Axelson O, Baranski B, Palus J, Wyszynska K (1993) Increased urinary excretion of the oxidative DNA adduct, 8-hydroxydeoxyguanosine, as a possible early indicator of occupational cancer hazards in the asbestos, rubber, and azo-dye industries. Polish J Occup Med Environ Health 6:357–368
Verhagen H, Poulsen HE, Loft S, van Poppel G, Willems MI, van Bladeren PJ (1995) Reduction of oxidative DNA-damage in man by Brussels sprouts. Carcinogenesis 16:969–970
Fraga CG, Motchnik PA, Shigenaga MK, Heibock HJ, Jacob RA, Ames BN (1991) Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci USA 88:11003–11006
van Poppel G, Poulsen HE, Loft S, Verhagen H (1995) No influence of beta-carotene on oxidative DNA damage in male smokers. J Natl Cancer Inst 87:310–311
Prestera T, Holtzclaw WD, Zhang Y, Talalay P (1993) Chemical and molecular regulation of enzymes that detoxify carcinogens. Proc Natl Acad Sci USA 90:2965–2969
Zhang Y, Kensler TW, Cho CG, Posner GH, Talalay P (1994) Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc Natl Acad Sci USA 91:3147–3150
Malins DC, Haimanot R (1991) Major alterations in the nucleotide structure of DNA in cancer of the female breast. Cancer Res 51:5430–5432
Malins DC, Holmes EH, Polissar NL, Gunselman S (1993) The etiology of breast cancer. Characteristic alterations in hydroxyl radical-induced DNA base lesions during oncogenesis with potential for evaluating incidence risk. Cancer Lett 71:3036–3042
Jaruga P, Zastawny TH, Skokowski J, Dizdaroglu M, Olinski R (1994) Oxidative DNA base damage and antioxidant enzyme activities in human lung cancer. FEBS Lett 341:59–64
Nagashima M, Tsuda H, Takenoshita S, Nagamachi Y, Hirohashi S, Yokota J, Kasai H (1995) 8-hydroxydeoxyguanosine levels in DNA of human breast cancer are not significantly different from those of non-cancerous breast tissues by the HPLC-ECD method. Cancer Lett 90:157–162
Shimoda R, Nagashima M, Sakamoto M, Yamaguchi N, Hirohashi S, Yokota J, Kasai H (1994) Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis. Cancer Res 54:3171–3172
Okamoto K, Toyokuni S, Uchida K, Ogawa O, Takenewa J, Kahehi Y, Kinoshita H, Hattori-Nakakuki Y, Hiai H, Yoshida O (1994) Formation of 8-hydroxy-2′deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in human renal-cell carcinoma. Int J Cancer 58:825–829
Cao E-H, Wang J-J (1993) Oxidative damage to DNA: levels of thymine glycol and thymidine glycol in neoplastic human urines. Carcinogenesis 14:1359–1362
Olinski R, Zastawny TH, Foksinski M, Barecki A, Dizdaroglu M (1995) DNA base modifications and antioxidant enzyme activities in human benign prostatic hyperplasia. Free Radic Biol Med 18:807–813
Carmichael PL, Hewer A, Osborne MR, Strain AJ, Phillips DH (1995) Detection of bulky DNA lesions in the liver of patients with Wilson's disease and primary haemochromatosis. Mutation Res 326:235–243
Yamamoto F, Kasai H, Togashi Y, Takeichi N, Hori T, Nishimura S (1993) Elevated level of 8-hydroxydeoxyguanosine in DNA of liver, kidney, and brain of Long-Evans cinnamon rats. Jpn J Cancer Res 84:508–511
Hagen TM, Huang S, Curnutte J, Fowler P, Martinez V, Wehr CM, Ames BN, Chisari FV (1994) Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma. Proc Natl Acad Sci USA 91:12808–12812
Takeuchi T, Morimoto K (1993) Increased formation of 8-hydroxydeoxyguanosine, an oxidative DNA damage, in lymphoblasts Fanconi's anemia pateints due to possible catalase deficiency. Carcinogenesis 14:1115–1120
Brown RK, McBurney A, Lunec J, Kelly FJ (1995) Oxidative damage to DNA in patients with cystic fibrosis. Free Radic Biol Med 18:801–806
Taylor A, Lipman RD, Jahngen-Hodge J, Plamer V, Smith D, Padhye N, Dallal GE, Cyr DE, Laxman E, Shepard D, Morrow F, Salomon R, Perrone G, Asmundsson G, Meydani M, Blumberg J, Mune M, Harrison DE, Archer JR, Shigenaga M (1995) Dietary calorie restriction in the Emory mouse: effects on lifespan, eye lens cataract prevalence and progression, levels of ascorbate, glutathione, glucose, and glycohemoglobin, tail collagen break time, DNA and RNA oxidation, skin integrity, fecundity, and cancer. Mech Ageing Dev 79:33–57
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Loft, S., Poulsen, H.E. Cancer risk and oxidative DNA damage in man. J Mol Med 74, 297–312 (1996). https://doi.org/10.1007/BF00207507
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00207507