Skip to main content
SpringerLink
Log in

Oxidative DNA Damage Profiles in Mammalian Cells

  • Conference paper
Risk and Progression Factors in Carcinogenesis

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 143))

Abstract

Reactive oxygen species (ROS) are formed inside cells not only under the influence of exogenous agents (visible light, ionizing radiation, and many oxidants such as peroxides or quinones), but also under normal (physiological) conditions as byproducts of oxygen metabolism and other cellular redox reactions (Pryor 1986; Halliwell and Gutteridge 1986; Sies 1986; Clayson et al. 1994). ROS such as hydroxyl radicals and singlet oxygen are a serious threat to the integrity of the cellular genome, since they efficiently react with DNA to generate many types of DNA modifications, at least some of which are pre- mutagenic (Breimer 1990; Halliwell and Aruoma 1991; Epe 1991; Feig et al. 1994). Steady-state levels of 8-hydroxyguanine (8-oxoG) and other oxidative DNA base modifications observed in untreated cells indicate that the various cellular defense and DNA repair systems (Demple and Harrison 1994) do not completely eliminate the mutagenic risk associated with ROS formation even under normal growth conditions. This led to the assumption that oxidative DNA damage is a causal or ancillary risk factor for the development of cancer and several age-correlated degenerative diseases (Ames 1983; Wallace 1992; Gutteridge 1993). A strategy to verify this hypothesis and to quantify the mutagenic risk associated with oxidative DNA damage could be to determine (a) what type of oxidative DNA damage profile (pattern of DNA modifications) is generated in the cells under the conditions of interest and (b) the mutagenicity associated with this damage profile. Then, the quantification of any suitable marker modification of this damage profile should allow an estimation of the mutagenicity to be expected.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Akman SA, Forrest GP, Doroshow JH, Dizdaroglu M (1991) Mutation of potassium permanganate- and hydrogen peroxide-treated plasmid pZ189 replicating in CV-1 monkey kidney cells. Mutat Res 261: 123–130

    Article  PubMed  CAS  Google Scholar 

  • Ames BN (1983) Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science 221: 1256–1264

    Article  PubMed  CAS  Google Scholar 

  • Ballmaier D, Epe B (1995) Oxidative DNA damage induced by potassium bromate under cell-free conditions and in mammalian cells. Carcinogenesis 16: 335–342

    Article  PubMed  CAS  Google Scholar 

  • Boiteux S, Gajewski E, Laval J, Dizdaroglu M (1992) Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization. Biochemistry 31: 106–110

    Article  PubMed  CAS  Google Scholar 

  • Boiteux S (1993) Properties and biological functions of the NTH and FPG proteins of Escherichia coli: two DNA glycosylases that repair oxidative damage in DNA. Photochem Photobiol B 19: 87–96

    Article  CAS  Google Scholar 

  • Breimer (1990) Molecular mechanisms of oxygen radical carcinogenesis and mutagenesis: the role of base damage. Molec Carcinogenesis 3: 188–197

    Article  CAS  Google Scholar 

  • Cantoni O, Sestili P, Cattabeni F, Bellomo G, Pou S, Cohen M, Cerutti P (1989) Calcium chelator quin 2 prevents hydrogen-peroxide-induced DNA breakage and cytotoxicity. Eur J Biochem 182: 209–212

    Article  PubMed  CAS  Google Scholar 

  • Clayson DB, Mehta R, Iverson F (1994) Oxidative DNA damage - the effects of certain genotoxic and operationally non-genotoxic carcinogens. Mutat Res 317: 25–42

    PubMed  CAS  Google Scholar 

  • Costa de Oliveira R, Ribeiro DT, Nigro RG, Di Mascio P, Menck CFM (1992) Singlet oxygen induced mutation spectrum in mammalian cells. Nucleic Acids Res 20: 4319–4323

    Article  Google Scholar 

  • Decuyper-Debergh D, Piette J, van de Vorst A (1987) Singlet oxygen-induced mutations in M13 lacZ phage DNA. EMBO J 6: 3155–3161

    PubMed  CAS  Google Scholar 

  • Demple B, Harrison L (1994) Repair of oxidative damage to DNA: enzymology and biology. Annu Rev Biochem 63: 915–948

    Article  PubMed  CAS  Google Scholar 

  • Di Mascio P, Sies H (1989) Quantification of singlet oxygen generated by thermolysis of 3,3’-(l,4-naphthylidene)dipropionate. Monomol and dimol photoemission and the effects of 1, 4-diazabicyclo [2.2.2]octane. J Am Chem Soc 111: 2909–2914

    Article  CAS  Google Scholar 

  • Epe B (1991) Genotoxicity of singlet oxygen. Chem Biol Interact 80: 239–260

    Article  PubMed  CAS  Google Scholar 

  • Epe B, Hegler J (1994) Oxidative DNA damage: endonuclease fingerprinting. Methods Enzymol 234: 122–131

    Article  PubMed  CAS  Google Scholar 

  • Epe B, Mützel P, Adam W (1988) DNA damage by oxygen radicals and excited state species: a comparative study using enzymatic probes in vitro. Chem Biol Interact 67: 149–165

    Article  PubMed  CAS  Google Scholar 

  • Epe B, Pflaum M, Boiteux S (1993a) DNA damage induced by photosensitizers in cellular and cell-free systems. Mutat Res 299: 135–145

    Article  PubMed  CAS  Google Scholar 

  • Epe B, Henzl H, Adam W, Saha-Möller CR (1993b) Endonuclease-sensitive DNA modifications induced by acetone and acetophenone as photosensitizers. Nucleic Acids Res 21: 863–869

    Article  PubMed  CAS  Google Scholar 

  • Epe B, Häring M, Ramaiah D, Stopper H, Adam W, Abou-Elzahab MM, Saha-Möller CR (1993c) DNA damage induced by furocoumarin hydroperoxides plus UV (360 nm). Carcinogenesis 14: 2271–2276

    Article  PubMed  CAS  Google Scholar 

  • Feig DI, Sowers LC, Loeb LA (1994) Reverse chemical mutagenesis: identification of the mutagenic lesions resulting from reactive oxygen species-mediated damage to DNA. Proc Natl Acad Sci USA 91: 6609–6613

    Article  PubMed  CAS  Google Scholar 

  • Gutteridge JMC (1993) Free radicals in disease processes: a compilation of cause and consequences. Free Radical Res Commun 19: 141–158

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B, Gutteridge JM (1986) Oxygen free radicals and iron in relation to biology and medicine, some problems and concepts. Arch Biochem Biophys 246: 501–514

    Article  PubMed  CAS  Google Scholar 

  • Häring M, Rüdiger H, Demple B, Boiteux S, Epe B (1994) Recognition of oxidized abasic sites by repair endonucleases. Nucleic Acids Res 22: 2010–2015

    Article  PubMed  Google Scholar 

  • Hess KM, Dix TA (1992) Evaluation of N-hydroxy-2-thiopyridone as a nonmetal dependent source of the hydroxyl radical ( HO’) in aqueous systems. Anal Biochem 206: 309–314

    Article  PubMed  CAS  Google Scholar 

  • Kurokawa Y, Maekawa A, Takahashi M, Hayashi Y (1990) Toxicity and carcinogenicity of potassium bromate - a new renal carcinogen. Environ Health Perspect 87: 309–335

    PubMed  CAS  Google Scholar 

  • Lindahl T (1990) Repair of intrinsic DNA lesions. Mutat Res 238: 305–311

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Meneghini R (1988) Genotoxicity of active oxygen species in mammalian cells. Mutat Res 195: 215–230 (1988)

    Google Scholar 

  • Moraes EC, Keyse SM, Pidoux M, Tyrrell RM (1989) The spectrum of mutations generated by passage of a hydrogen peroxide damaged shuttle vector plasmid through a mammalian host. Nucleic Acids Res 17: 8301–8312

    Article  PubMed  CAS  Google Scholar 

  • Müller E, Boiteux S, Cunningham RP, Epe B (1990) Enzymatic recognition of DNA modifications induced by singlet oxygen and photosensitizers. Nucleic Acids Res 18: 5969–5973

    Article  PubMed  Google Scholar 

  • Nakabeppu Y, Yamashita K, Sekiguchi M (1982) Purification and characterization of normal and mutant forms of T4 endonuclease V. Proc Natl Acad Sci USA 257: 2556–2562

    CAS  Google Scholar 

  • Pflaum M, Boiteux S, Epe B (1994) Visible light generates oxidative DNA base modifications in high excess of strand breaks in mammalian cells. Carcinogenesis 15: 297–300

    Article  PubMed  CAS  Google Scholar 

  • Pryor WA (1986) Oxy-radicals and related species: their formation, lifetimes, and reactions. Annu Rev Physiol 48: 657–667

    Article  PubMed  CAS  Google Scholar 

  • Retèl J, Hoebee B, Braun JEF, Lutgerink JT, van der Akker E, Wanamarta AH, Joenje H, Lafleur MVM (1993) Mutational specificity of oxidative DNA damage. Mutât Res 299: 165–182

    PubMed  Google Scholar 

  • Salditi M, Braunstein SN, Camerini-Otero RD, Franklin RM (1972) Structure and synthesis of a lipid-containing bacteriophage. Virology 48: 259–262

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Sies H (1986) Biochemistry of oxidative stress. Angew Chem Int Ed Engl 25: 1058–1071

    Article  Google Scholar 

  • Steenken S (1989) 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

    Article  CAS  Google Scholar 

  • Tchou J, Bodepudi V, Shibutani S, Antoshechkin I, Miller J, Grollman AP, Johnson F (1994) Substrate specificity of Fpg protein. J Biol Chem 269: 15318–15324

    PubMed  CAS  Google Scholar 

  • Tindall KR, Stankowski LF Jr, Machanoff R, Hsie AW (1986) Analyses of mutation in pSV2gpt-transformed CHO cells. Mutat Res 160: 121–131

    Article  PubMed  CAS  Google Scholar 

  • Tudek B, Laval J, Boiteux S (1993) SOS-independent mutagenesis in lacZ induced by methylene blue plus visible light. Mol Gen Genet 236: 433–439

    Article  PubMed  CAS  Google Scholar 

  • Wallace SS (1988) AP endonucleases and DNA glycosylases that recognize oxidative DNA damage. Environ Mol Mutagen 12: 431–477

    PubMed  CAS  Google Scholar 

  • Wallace DG (1992) Mitochondrial genetics: a paradigm for aging and degenerative diseases? Science 256: 628–632

    Article  PubMed  CAS  Google Scholar 

  • Waters LC, Sikpi MO, Preston RJ, Mitra S, Jaberaboansari A (1991) Mutations induced by ionizing radiation in a plasmid replicated in human cells. Radiat Res 127: 190–201

    Article  Google Scholar 

  • Weis M, Kass GE, Orrenius S (1994) Further characterization of the events involved in mitochondrial Ca2+ release and pore formation by prooxidants. Biochem Pharmacol 47: 2147–2156

    Article  PubMed  CAS  Google Scholar 

  • Wood ML, Dizdaroglu M, Gajewski E, Essigmann JM (1990) Mechanistic studies of ionizing radiation and oxidative mutagenesis: genetic effects of a single 8-hydroxy-guanine (7-hydro-8-oxoguanine) residue inserted at a unique site in a viral genome. Biochemistry 29: 7024–7032

    Article  PubMed  CAS  Google Scholar 

  • Zhivotovsky B, Wade D, Gahm A, Orrenius S, Nicotera P (1994) Formation of 50 kbp chromatin fragments in isolated liver nuclei is mediated by protease and endonuclease activation. FEBS Lett 351: 150–154

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, University of Mainz, Staudinger Weg 5, 55099, Mainz, Germany

    D. Ballmaier, M. Pflaum, C. Kielbassa & B. Epe

Authors
  1. D. Ballmaier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Pflaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Kielbassa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. Epe
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pathologisches Institut, der Universität Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany

    H. K. Müller-Hermelink

  2. Institut für Pharmakologie und Toxikologie, der Universität Würzburg, Versbacher Straße 9, 97078, Würzburg, Germany

    H.-G. Neumann  & W. Dekant  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin · Heidelberg

About this paper

Cite this paper

Ballmaier, D., Pflaum, M., Kielbassa, C., Epe, B. (1997). Oxidative DNA Damage Profiles in Mammalian Cells. In: Müller-Hermelink, H.K., Neumann, HG., Dekant, W. (eds) Risk and Progression Factors in Carcinogenesis. Recent Results in Cancer Research, vol 143. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60393-8_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60393-8_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64385-9

  • Online ISBN: 978-3-642-60393-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation