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Chromosome Damage and Repair pp 585–595Cite as

Some Parameters Affecting DNA Damage and Their Relevance to the Action of Chemical Carcinogens

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Part of the book series: NATO Advanced Study Institutes Series ((NSSA,volume 40))

Abstract

The observation that chemical carcinogens will react with the genetic material of cells has provided a rational basis on which to build an understanding of their mutagenic action and possibly also of their carcinogenic action. In this paper the interactions of carcinogenic methylating and ethylating agents with nucleic acids will be considered in some detail. Over the past decade or so these compounds have been investigated extensively. Firstly, because of the extent to which they react with macromolecules, with the relative ease of their detection by radioactive tracer techniques, and secondly, because the transfer of a simple alkyl group seemed to offer probably the best long term possibilities for the interpretation of the actions of these carcinogens at the molecular level1. Further, their potential as mutagens and the remarkable tissue-specificity of tumour formation by the N-nitroso compounds makes them vry suitable as probes in studies of the initiation of malignant change2.

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References

  1. G.P. Margison and P.J. O’Connor, Nucleic acid modification by N-nitroso compounds in: “Chemical Carcinogens and DNA”, P.L. Grover ed. CRC Press, Boca Raton (1979) pill.

    Google Scholar 

  2. P.J. O’Connor, R. Saffhill and G.P. Margison, N-nitroso compounds: Biochemical Mechanisms of action in: “Environmental Carcinogenesis”, P. Emmelot and E. Kriek eds. Elsevier/North Holland Biomedical Press, Amsterdam (1979) p73.

    Google Scholar 

  3. A. Loveless, Possible relevance of 0–6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosoamides, Nature (London) 223: 206 (1969).

    CAS  Google Scholar 

  4. P.N. Magee, R. Montesano and R. Preussmann, N-nitroso compounds and related carcinogens in “Chemical Carcinogens” C.E. Searle ed. A.C.S. Monographs 173, Amer.Chem.Soc., Washington DC (1976) p491.

    Google Scholar 

  5. P.J. O’Connor, Interactions of chemical carcinogens with macro-molecules. J.Clin.Oncology and Cancer Res, in press 1980.

    Google Scholar 

  6. T. Lindahl, DNA glycosylases, endonucleases for AP-sites and base-excision repair. Prog.Nucleic Acid Res.Mol.Biol. 22: 135 (1979).

    Article  CAS  PubMed  Google Scholar 

  7. G.P. Margison, J.M. Margison and R. Montesano, Methylated purines in the deoxyribonucleic acid of various Syrian golden hamster tissues after administration of hepatocarcinogenic doses of dimethylnitrosamine. Biochem.J. 157: 627 (1976).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. G.P. Margison, J.A. Swindell, C.H. Ockey and A.W. Craig, The eff-ect of a single dose of dimethylnitrosamine in the Chinese ham-ster and the persistence of DNA alkylation products in selected tissues. Carcìnogenesis 1: 91 (1980).

    Article  CAS  PubMed  Google Scholar 

  9. W. Warren, A.R. Crathorn and K.V. Shooter, The stability of meth-ylated purines and of methylphosphotriesters in the DNA of V79 cells after treatment with N-methyl-N-nitrosourea. Biochim. Biophys.Acta, 563: 82 (1979).

    Article  CAS  PubMed  Google Scholar 

  10. L.L. Gerschman and D.B. Ludlum, The properties of O –methylguanine in templates for RNA, polymerase. Biochim.Biophys.Acta, 308: 310 (1973).

    Article  Google Scholar 

  11. P.J. Abbott and R. Saffhill, DNA synthesis with methylated poly-(dC-dG) templates. Evidence for a competitive nature of miscod-ing by 0-methylguanine. Biochim.Biophys.Acta. 562: 51 (1979).

    Article  CAS  PubMed  Google Scholar 

  12. P.D. Lawley and D.J. Orr, Specific excision of methylated products from the DNA of E.coli treated with MNNG. Chem.-Biol.Interactions 2: 154 (1970).

    Article  CAS  Google Scholar 

  13. P. J. OCONNOR, , M. J. Capps and A.W. Craig, Comparative studies of the hepatocarcinogen N, N-dimethyintrosamine in vivo: reaction sites in rat liver DNA and the significance of their relative stability. Br. J.Cancer. 27:153(1973).

    Google Scholar 

  14. A.E. Pegg and G. Hui, Formation and subsequent removal of 06- methylguanine from DNA in rat liver and kidney after small doses of dimethylnitrosamine. Biochem.J. 173: 739 (1978).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. R. Montesano, H. Brésil, G. Planche-Martel, G.P. Margison and A.E. Pegg, Effect of chronic treatment of rats with dimethylnitrosamine on the removal of 06-methylguanine from DNA. Cancer Res. 40: 452 (1980).

    CAS  PubMed  Google Scholar 

  16. J.A. Swenberg, H.K. Cooper, J. Bücheler and P. Kleihues, 1,2Dimethylhydrazine-induced methylation of DNA bases in various rat organs and the effect of pretreatment with disulfiram Cancer Res. 39: 465 (1979).

    CAS  Google Scholar 

  17. K.J. Rogers and A.E. Pegg, Formation of 06-alkylguanine by alkylation of rat liver, colon and kidney following administration of 1,2-dimethylhydrazine. Cancer Res. 37: 4082 (1977).

    CAS  PubMed  Google Scholar 

  18. P.J. O’Connor, G.P. Margison, R. Montesano, J.D. Buckley, Y-H, Chu, D.P. Cooper, R.A. Smith, N.J. Curtin, K. Snell, J. Ashby, C. Bradbrook and J.A. Styles, The enhanced repair of Ó-alkylguanine in mammalian systems (this volume).

    Google Scholar 

  19. J.W. Nicoll, P.F. Swann and A.E. Pégg, Effect of dimethylnitrosamine on the persistence of methylated guanines in rat liver and kidney DNA. Nature (London) 254: 261 (1975).

    CAS  Google Scholar 

  20. R. Goth and M.F. Rajewsky, Persistence of 06-ethylguanine in rat brain DNA: correlation with nervous system-specific carcinogenesis. Proc.Natl.Acad.Sci.U.S.A. 71: 639 (1974).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. G.P. Margison and P. Kleihues, Chemical carcinogenesis in the nervous system: preferential accumulation of 06-methylguanine in rat brain DNA during repetitive administration of N-methylN-nitrosourea. Biochem.J. 148: 521 (1975).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. S. Ivankovic, Experimental prenatal carcinogenesis in “Transpla-cental Carcinogenesis” L. Tomatis and U. Mohr eds. IARC, Lyon 1973, p92.

    Google Scholar 

  23. G.P. Margison, A.J. Likhachev and G.F. Kolar, In vivo alkylation of foetal, maternal and normal rat tissue nucleic acids by 3-methyl-l-phenyltriazene. Chem.-Biol.Interactions 25:345 (1979).

    Article  CAS  Google Scholar 

  24. A.J. Likhachev, G.P. Margison and R. Montesano, Alkylated purines in the DNA of various rat tissues after administration of 1,2dimethylhydrazine. Chem.-Biol.Interactions 18: 235 (1977).

    Article  CAS  Google Scholar 

  25. R. Cox and C.C. Irving, Selective accumulation of 06-methylguanine in DNA of rat bladder epithelium after intravesical administration of N-methyl-N-nitrosourea. Cancer Lett. 3: 265 (1977).

    Article  CAS  Google Scholar 

  26. R. Cox and C.C. Irving, 06-met)iylguanîne accumulates in the DNA of mammary glands after administration of Nmethyl-N-nitrosourea to rats. Cancer Lett. 6: 273 (1979).

    Article  CAS  PubMed  Google Scholar 

  27. J.W. Nicoll, P.F. Swann and A.E. Pegg, The accumulation of 06-methylguanine in the liver and kidney of rats treated with di-methylnitrosamine for a short and a long period. Chem.-Biol. Interactions 16: 301 (1977).

    Article  CAS  Google Scholar 

  28. H.K. Cooper, E. Hauenstein, G.F. Kolar and P. Kleihues, DNA alkylation and oncogenesis by 3,3-dimethyl-l-phenyltriazene. Acta Neuropathol(Berl) 43: 105 (1978).

    Article  CAS  Google Scholar 

  29. V.M. Craddock, Induction of liver tumours in rats by a single treatment with nitroso-compounds given after partial hepatectomy. Nature (London) 245: 386 (1973).

    Article  CAS  Google Scholar 

  30. A.W. Pound and T.A. Lawson, Partial hepatectomy and toxicity of dimethylnitrosamine and carbontetrachloride in relation to the carcinogenic action of dimethylnitrosamine. Br.J.Cancer 32: 596 (1975).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. B. Terracini and P.N. Magee, Renal tumours in rats following in-jection of dimethylnitrosamine at birth. Nature (London) 202: 502 (1964).

    Article  CAS  Google Scholar 

  32. L. Tomatis and F. Cefis, The effects of multiple and single administration of dimethylnitrosamine to hamsters. Tumori 53: 447 (1967).

    Article  CAS  PubMed  Google Scholar 

  33. P.D. Lawley, Methylation of DNA by carcinogens: some applications of chemical analytical methods in “Screening Tests in Chemical Carcinogenesis” R. Montesano, H. Bartsch and L. Tomatis eds. IARC, Lyon 1976, p181.

    Google Scholar 

  34. J.V. Frei, D.H. Swenson, W. Warren and P.D. Lawley, Alkylation of DNA in vivo in various organs of C57B1 mice by the carcinogens N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea and ethylmethane-sulphonate in relation to the induction of thymic lymphoma. Biochem.J. 174: 1031 (1978).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. H.K. DeMunter, L. Den Engelse, and P. Emmelot, Studies on lung tumours IV. Correlation between [H3]-thymidine labelling of lung and liver cells and tumour formation in GRS/A and C3Hf/A male mice following administration of dimethylnitrosamine. Chem.-Biol.Interactions 24: 299 (1979).

    Article  CAS  Google Scholar 

  36. L. Den Engelse, The formation of methylated bases in DNA by dimethylnitrosamine and its relation to differences in the formation of tumours in the livers of GR and C3Hf mice. Chem.-Biol.Inter-actions 8: 329 (1974).

    Article  Google Scholar 

  37. P. Kleihues, S. Bamborschke and G. Doerjev, Persistence of alkyla-ted bases in the Mongolian gerbil (Meriones unguiculatus) following a single dose of methylnitrosourea. Carcinogenesis 1: 111 (1980).

    Article  CAS  PubMed  Google Scholar 

  38. P.J. Abbott and R. Saffhill, DNA synthesis with methylated poly(dA-dT) templates: possible role of Ó -methylthymidine as a pranutagenic base. Nucleic Acids Res 4: 761 (1977).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  39. R. Saffhill and P.J. Abbott, Formation of 02-methylthymine in poly(dA-dT) on methylation with N-methyl-N-nitrosourea and dimethyl sulphate. Evidence that Ó -methylthymine does not mis-code during DNA synthesis. Nucleic Acids Res. 5: 1971 (1978).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. B. Singer, H. Fraenkel-Conrat and J.T. Kugmierek, PrparatioR and template activities of polynucleotides containing O - and O - alkyluridine. Proc.Natl.Acad.Sci.U.S.A. 75: 1722 (1978).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  41. W.J. Bodell, B. Singer, G.H. Thomas and J.E. Cleaver, Evidence for removal at different rates of O-ethylpyrimidines and ethylphosphotriesters in two human fibroblasts. Nucleic Acids Res 6: 2819 (1979).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  42. R.F. Newbold, W. Warren, A.S.C. Medcalf and J. Amos, Mutagenicity of carcinogenic methylating agents is associated with a specific DNA modification. Nature (London) 283: 596 (1980).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester, M2O 9BX, UK

    P. J. O’Connor

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  1. P. J. O’Connor
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Editors and Affiliations

  1. Norwegian Defense Research Establishment, Kjeller, Norway

    Erling Seeberg

  2. University of Bergen, Bergen, Norway

    Kjell Kleppe

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© 1981 Plenum Press, New York

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O’Connor, P.J. (1981). Some Parameters Affecting DNA Damage and Their Relevance to the Action of Chemical Carcinogens. In: Seeberg, E., Kleppe, K. (eds) Chromosome Damage and Repair. NATO Advanced Study Institutes Series, vol 40. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-7956-0_71

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  • DOI: https://doi.org/10.1007/978-1-4684-7956-0_71

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