Skip to main content
SpringerLink
Log in

A discussion of mechanisms of NO genotoxicty: Implication of inhibition of DNA repair proteins

  • Chapter
  • First Online:
Reviews of Physiology Biochemistry and Pharmacology, Volume 131

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 131))

  • 57 Accesses

Abstract

The involvement of NO in genotoxicity and carcinogenic mechanisms may be varied. On one hand NO can form RNOS which can modify DNA. Most of these experiments were done under very high concentrations of NO and RNOS and may have little or nothing to do with in vivo mechanisms. However, NO can affect DNA specific repair systems even in whole cells at lower NO and RNOS concentrations which might enhance the damage of another agent. Though NO might alter DNA directly, the most likely involvement of its genotoxic action is through the increase in sensitivity to other mutagenic agents. From this discussion, it appears that the primary source of RNOS is from iNOS. Thus genotoxicity either by direct chemical alteration of DNA or interference with the repair system would be from an iNOS source.

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

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Arroyo PL, Hatch-Pigott V, Mower HF, Cooney RV (1992) Mutagenicity of nitric oxide and its inhibition by antioxidants. Mutation Res 281:193–202

    Article  PubMed  Google Scholar 

  • Caldecott KW, McKeown CK, Tucker JD, Ljungquist S, Thompson LH (1994) An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III. Mol Cell Biol 14:68–76

    PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Engler MJ, Richardson CC (1982) The enzymes. 15B:3–29

    Google Scholar 

  • Feldman PL, Griffith OW, Stuehr DJ (1992) The surprising life of nitric oxide. Chem Eng News December 20:26–38

    Google Scholar 

  • Graziewicz M, Wink DA, Laval F (1996) Nitric oxide inhibits DNA ligase activity. Potential mechanisms for No-mediated DNA damage. Carcinogenesis 17:2501–2505

    PubMed  Google Scholar 

  • Griffith OW, Stuehr DJ (1995) Nitric oxide synthases: properties and catalytic mechanism. Annu Rev Physiol 57:707–736

    Article  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JMC (1989) in Free radicals in biology and medicine. 416–509, Clarendon Press, Oxford

    Google Scholar 

  • Higashitani A, Tabata S, Endo H, Hotta Y (1990) Purification of DNA ligases from mouse testis and their behaviour during meiosis. Cell Struct Funct 15:67–72

    PubMed  Google Scholar 

  • Hogg N, Kalyanaraman B, Joseph J, Struck A, Parthasarathy S (1993) Inhibition of low-density lipoprotein oxidation by nitric oxide. Potential role in atherogenesis. FEBS Lett 334:170–174

    Article  PubMed  Google Scholar 

  • Ignarro LJ (1990) Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 30:535–560

    PubMed  Google Scholar 

  • Inoue S, Kawanishi S (1995) Oxidative DNA damage induced by simultaneous generation of nitric oxide and superoxide. FEBS Lett 371:86–88

    Article  PubMed  Google Scholar 

  • Ischiropoulous H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD, Beckman JS (1992) Peroxynitrite-mediated tyrosine nitrosation catalyzed by superoxide dismutase. Arch Biochem Biophys 298:431–437

    Article  PubMed  Google Scholar 

  • Juedes MJ, Wogan GN (1996) Peroxynitrite-induced mutation spectra of pSP189 following replication in bacteria and in human cells. Mutat Res 349:51–61

    PubMed  Google Scholar 

  • Kanner, J, Harel S, Granit R (1991) Nitric oxide as an antioxidant. Arch Biochem Biophys 289:130–136

    PubMed  Google Scholar 

  • King PA, Anderson VE, Edwards JO, Gustafson G, Plumb RC, Suggs JW (1992). A stable solid state that generates hydroxyl radical upon dissolution in equeous solutions: Reaction with proteins and nucleic acids. J Am Chem Soc 114:5430–5432

    Article  Google Scholar 

  • Koppenol WH (1996) Thermodynamics of reactions involving Nitriogen-Oxygen Compounds. Methods Enzymol 268:3–12

    PubMed  Google Scholar 

  • Koppenol WH, Moreno JJ, Pryor WA, Ischiropoulus H, Beckman JS (1992) Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol 5:834–842

    Article  PubMed  Google Scholar 

  • Kroncke K-D, Fechsel K, Schmidt T, Zenke FT, Dasting I, Wesener JR, Bettermann H, Breunig KD, Kolb-Bachofen V (1994) Nitric oxide destoys zinc-finger clusters inducing zinc release from metallothionein and inhibition of the zinc finger-type yeast transcription activator LAC9. Biochem Biophys Res Commun 200:1105–1110

    PubMed  Google Scholar 

  • Laval J (1996) Role of DNA repair enzymes in the cellular resistance to oxidative stress. Path Biol (Paris) 44:14–24

    Google Scholar 

  • Laval F, Wink DA (1994) Inhibition by nitric oxide of the repair protein O6-methylguanin-DNA-methyltransferase. Carcinogenesis 15:443–447

    PubMed  Google Scholar 

  • Li C, Goodchild J, Baril EF (1994) DNA ligase I is associated with the 21 S complex of enzymes for DNA synthesis in HeLa cells. Nucleic Acids Res 22:632–638

    PubMed  Google Scholar 

  • Lindahl T, Barnes DE (1992) Mammalian DNA ligases. Annu Rev Biochem 61:251–281

    Article  PubMed  Google Scholar 

  • Ling-Ling C, Nakamura T, Nakatsu Y, Sakumi K, Hayakawa H (1992) Specific amino acid sequences required for O6-methylguanine-DNA-methyltransferase activity: analysis of three residues at or near the methyl acceptor site. Carcinogenesis 13:837–843

    PubMed  Google Scholar 

  • Liu RH, Baldwin B, Tennant BC, Hotchkiss JH (1991) Elevated formation of nitrate and N-nitrosodimethylamine in woodchicks (Marmota monax) associated with chronic woodchuck hepatitis virus infection. Cancer Res 51:3925–3929

    PubMed  Google Scholar 

  • Liu RH, Jacob JR, Tennant BD, Hotchkiss JH (1992) Nitrite and nitrosamine synthesis by hepatocytes isolated from normal woodchucks (Marmota monax) and woodchucks chronically infected with woochuck hepatitis virus. Cancer Res 52:4139–4143

    PubMed  Google Scholar 

  • Ljungquist S, Kenne K, Olsso L, Sandstrom M (1994) Altered DNA ligase III activity in the CHO EM9 mutant. Mutat Res 314:177–186

    PubMed  Google Scholar 

  • Marletta MA (1988) Mammalian synthesis of nitrite, nitrate, nitric oxide and N-nitrosating agents. Chem Res Toxicol 1:249–257

    Article  PubMed  Google Scholar 

  • Marletta MA (1993) Nitric oxide synthase structure and mechanism. J Biol Chem 268:12231–12234

    PubMed  Google Scholar 

  • Messmer UK, Ankarcrona M, Nicotera P, Brune B (1994) p53 expression in nitric oxide-induced apoptosis. FEBS Lett 355:23–26

    Article  PubMed  Google Scholar 

  • Miles AM, Gibson M, Krishna M, Cook JC, Pacelli R, Wink DA, Grisham MB (1995) Effects of superoxide on nitric oxide-dependent N-nitrosation reactions. Free Radic Res 233:379–390

    Google Scholar 

  • Miles AM, Bohle DS, Glassbrenner PA, Hansert B, Wink DA, Grisham MB (1996) Modulation of superoxide-dependent oxidation and hydroxylation reactions by nitric oxide. J Biol Chem 271:40–47

    PubMed  Google Scholar 

  • Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142

    PubMed  Google Scholar 

  • Nathan C, Xie Q (1994) Regulation of biosynthesis of nitric oxide. J Biol Chem 269:13725–13728

    PubMed  Google Scholar 

  • Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR (1992) DNA damage and mutation in human cells exposed to nitric oxide. Proc Natl Acad Sci USA 89:3030–3034

    PubMed  Google Scholar 

  • O'Connor T, Graves RV, Murcia G, Castaing B, Laval J (1993) Fpg protein of Escherichia coli is a zinc finger protein whose cystiene residues have a structural and/or functional role. J Biol Chem 268:9063–9070

    PubMed  Google Scholar 

  • Pacelli R, Krishna MC, Wink DA, Mitchell JB (1994) Nitric oxide protects DNA from hydrogen peroxide-induced double strand cleavage. Proc Am Assoc Cancer Res 35:540

    Google Scholar 

  • Pryor WA, Jin X, Squadrito G (1994) One and two electron oxidations of methionine by peroxynitrite. Proc Natl Acad Sci USA 92:11173–11177

    Google Scholar 

  • Pryor WA, Squadrito GL (1996) The chemistry of peroxynitrite and peroxynitrous acid: products from the reaction of nitric oxide with superoxide. Am J Phys. 268:L699–721

    Google Scholar 

  • Radi R, Beckman JS, Bush KM, Freeman BA (1991) Peroxynitrite oxidation of sulfhydryls: the cytotoxic potential of superoxide and nitric oxide. J Biol Chem 266:4244–4250

    PubMed  Google Scholar 

  • Routledge MN, Wink DA, Keefer LK, Dipple A (1993) Mutations induced by saturated aqueous nitric oxide in the pSP189 supF gene in human Ad293 and E. coli MBM7070 cells. Carcinogenesis 14:1251–1254

    PubMed  Google Scholar 

  • Routledge MN, Mirsky FJ, Wink DA, Keefer LK, Dipple A (1994a) Nitrite-induced mutations in a forward mutation assay: influence of nitrite concentration and pH. Mutat Res 322:341–346

    Article  PubMed  Google Scholar 

  • Routledge MN, Wink DA, Keefer LK, Dipple A (1994b) DNA sequence changes induced by two nitric oxide donor drugs in the supF assay. Chem Res Toxicol 7:628–632

    Article  PubMed  Google Scholar 

  • Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, Kirk M, Freeman BA (1994) Nitric oxide regulation of superoxide and peroxynitrite dependent lipid peroxidation: formation of novel nitrogen containing oxidized lipid derivatives. J Biol Chem 269:26066–26075

    PubMed  Google Scholar 

  • Salgo MG, Stone K, Squadrito GL, Battista JR, Pryor WA (1995) Peroxynitrite causes DNA nicks in plasmid pBR322. Biochem Biophys Res Commun 210:1025–1030

    Article  PubMed  Google Scholar 

  • Schmeidescamp M, Klevit RE (1994) zing finger diversity. Curr Opin Struct. Biol 4:28–35

    Google Scholar 

  • Schmutte Crideout WM III, Shen JC, Jones PA (1994) Mutagenicity of nitric oxide is not caused by deamination of cytosine or 5-methylcytosine in double-stranded DNA. Carcinogenesis 15:2899–2903

    PubMed  Google Scholar 

  • Tomkinson AE, Roberts E, Daly G, Totty NF, Lindahl T (1991) Three distinct DNA ligases in mammalian cells. J Biol Chem 266:21728–21735

    PubMed  Google Scholar 

  • Wei Y, Robins P, Carter K, Caldecott K, Pappin DJC, Yu G, Wang R, Shell BK, Nash RA, Schar P, Barnes DE, Haseltine WA, Lindahl T (1995) Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination. Mol Cell Biol 15:3206–3216

    PubMed  Google Scholar 

  • Williams DLH (1988). In: in Nitrosation. Cambridge University Press, New York, pp 173–194

    Google Scholar 

  • Wink DA, Laval J (1994) The Fpg protein, a DNA repair enzyme, is inhibited by the biomediator nitric oxide in vitro and in vivo. Carcinogenesis 15:2125–2129

    PubMed  Google Scholar 

  • Wink DA, Ford PC (1995) Nitric oxide reactions important to biological systems: a survey of some kinetics investigations. Methods: A Companion to Methods in Enzymology 14–20 Academic Press.

    Google Scholar 

  • Wink DA, Kasprzak KS, Maragos CM, Elespuru RK, Misra M, Dunams TM, Cebula TA, Koch WH, Andrews AW, Allen JS, Keefer LK (1991) DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254:1001–1003

    PubMed  Google Scholar 

  • Wink DA, Darbyshire JF, Nims RW, Saveedra JE, Ford PC (1993) Reactions of the bioregulatory agent nitric oxide in oxygenated aquious media: determination of the kinetics for oxidation and nitrosation by intermediates generated in the NO/O2 reaction. Chem Res Toxicol 6:23–27

    Article  PubMed  Google Scholar 

  • Wink DA, Nims RW, Darbyshire JF, Christodoulou D, Hanbauer I, Cox GW, Laval F, Laval J, Cook JA, Krishna MC, DeGraff W, Mitchell J B (1994a) Reaction kinetics for nitrosation of cysteine and glutathione in aerobic nitric oxide solutions at neutral pH. Insights into the fate and physiological effects of intermediates generated in the NO/O2 reaction. Chem Res Toxicol 7:519–525

    Article  PubMed  Google Scholar 

  • Wink DA, Hanbauer I, Laval F, Cook JA, Krishna MC, Mitchell JB (1994b) Nitric oxide protects against the cytotoxic effects of reactive oxygen species. Ann NY Acad Sci 738:265–278

    PubMed  Google Scholar 

  • Wink DA, Hanbauer I, Grisham MB, Laval F, Nims RW, Laval J, Cook JC, Pacelli R, Liebmann J, Krishna MC, Ford MC, Mitchell JB (1996) The chemical biology of NO. Insights into regulation, protective and toxic mechanisms of nitric oxide. Curr Top Cell Regul 34:159–187

    PubMed  Google Scholar 

  • Yermilov V, Rubio J, Becchi M, Friesen MD, Pignatelli B, Ohshima H (1995a) Formation of 8-nitroguanine by the reaction of guanine with peroxynitrite in vitro. Carcinogenesis 16:2045–2050

    PubMed  Google Scholar 

  • Yermilov V, Rubio J, Ohshima H (1995b) Formation of 8-nitroguanine in DNA treated with peroxynitrite in vitro and its rapid removal from DNA by depurination. FEBS Lett 376:207–210

    Article  PubMed  Google Scholar 

  • Zak P, Kleibl K, Laval F (1994) Repair of O6-methylguanine and O4-methylthymine by the purified human and rat O6-methylguanine-DNA methyltransferases. J Biol Chem 269:730–733

    PubMed  Google Scholar 

  • Zhang, J, Dawson VL, Dawson TM, Synder SH (1994) Nitric oxide activation of poly (ADP-ribose)synthetase in neurotoxicity. Science 263:687–689

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. U347 INSERM, Rue du Général Leclerc, 94276, Le Kremlin-Bicêtre, France

    F. Laval

  2. Radiation Biology Branch Bethesda, 20893, MD, USA

    D. A. Wink

  3. Groupe Réparation des Lésions Radio et Chimio-Induites, URA 147 CNRS, Institut Gustave-Roussy, F-94805, Villejuif, France

    J. Laval

Authors
  1. F. Laval
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. A. Wink
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Laval
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag

About this chapter

Cite this chapter

Laval, F., Wink, D.A., Laval, J. (1997). A discussion of mechanisms of NO genotoxicty: Implication of inhibition of DNA repair proteins. In: Reviews of Physiology Biochemistry and Pharmacology, Volume 131. Reviews of Physiology, Biochemistry and Pharmacology, vol 131. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-61992-5_8

Download citation

  • DOI: https://doi.org/10.1007/3-540-61992-5_8

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-61992-5

  • Online ISBN: 978-3-540-49585-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation