Advertisement

Introduction: DNA Damage and Repair

  • P. N. Magee
Part of the Basic Life Sciences book series

Abstract

The concept that cancer may be induced by the interaction of a carcinogen with DNA is widely accepted, although it is becoming increasingly clear that some carcinogens do not interact with DNA to a detectable extent. The carcinogens have been classified into two broad categories, genotoxic and non-genotoxic or epigenetic. Genotoxic carcinogens damage DNA, whereas epigenetic or non-genotoxic carcinogens appear to operate by other mechanisms, such as chronic tissue injury, immunosuppression, solid-state effects, hormonal imbalance, cocarcinogenicity, and promotion (1). This presentation will be concerned only with agents that cause DNA damage and repair.

Keywords

Partial Hepatectomy Xeroderma Pigmentosum Pyrimidine Dimer Chemical Carcinogenesis Methyl Methanesulfonate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Williams, G.M. 1980. Classification of genotoxic and epigenetic hepatocarcinogens using liver culture assays. Ann. N.Y. Acad. Sci. 349:273–282.PubMedCrossRefGoogle Scholar
  2. 2.
    Miller, E.C., and J.A. Miller. 1966. Mechanisms of chemical carcinogenesis: Nature of proximate carcinogens and interactions with macromolecules. Pharmacol. Rev. 18:805–838.PubMedGoogle Scholar
  3. 3.
    Westphal, H., and R. Dulbecco. 1968. Viral DNA in polyomaand SV40-transformed cell lines. Proc. Natl. Acad. Sci. USA 59:1158–1165.PubMedCrossRefGoogle Scholar
  4. 4.
    Temin, H., and S. Mizutani. 1970. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226:1211–1213.PubMedCrossRefGoogle Scholar
  5. 5.
    Baltimore, D. 1970. RNA-dependent DNA polymerase in virions of RNA tumor viruses. Nature 226:1209–1211.PubMedCrossRefGoogle Scholar
  6. 6.
    Shih, C., B.Z. Shilo, M.P. Goldfarb, A. Dannenberg, and R.A. Weinberg. 1979. Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. Proc. Natl. Acad. Sci. USA 76:5714–5718.PubMedCrossRefGoogle Scholar
  7. 7.
    Cooper, G.M., S. Okenquist, and S. Silverman. 1980. Transforming activity of DNA of chemically transformed and normal cells. Nature 284:418–421.PubMedCrossRefGoogle Scholar
  8. 8.
    Barrett, J.C., T. Tsutsui, and P.O.P. Ts’o. 1978. Neoplastic transformation induced by a direct perturbation of DNA. Nature 274:229–232.PubMedCrossRefGoogle Scholar
  9. 9.
    Cleaver, J.E. 1968. Defective repair replication of DNA in Xeroderma pigmentosum. Nature 218:652–656.PubMedCrossRefGoogle Scholar
  10. 10.
    Robbins, J.H., K.H. Kraemer, M.A. Lutzner, B.W. Festoff, and H.G. Coon. 1974. Xeroderma pigmentosum: An inherited disease with sun sensitivity, multiple cutaneous neoplasms, and abnormal DNA repair. Ann. Intern. Med. 80:221–248.PubMedGoogle Scholar
  11. 11.
    Cleaver, J.E., and D. Bootsma. 1975. Xeroderma pigmentosum: Biochemical and genetic characteristics. Ann. Rev. Genet. 9:19–38.PubMedCrossRefGoogle Scholar
  12. 12.
    Hart, R.W., R.B. Setlow, and A.D. Woodhead. 1977. Evidence that pyrimidine dimers in DNA can give rise to tumors. Proc. Natl. Acad. Sci. USA 74:5574–5578.PubMedCrossRefGoogle Scholar
  13. 13.
    Boveri, T.H. 1914. Zur Frage der Entstehung maligner Tumoren. Gustav Fischer: Yena. 64 pp.Google Scholar
  14. 14.
    Ames, B.N., W. Durston, E. Yamasaki, and F. Lee. 1973. Carcinogens are mutagens: A simple test system combining liver homogenates for activation and bacteria for detection. Proc. Natl. Acad. Sci. USA 70:2281–2285.PubMedCrossRefGoogle Scholar
  15. 15.
    McCann, J., E. Choi, E. Yamasaki, and B.N. Ames. 1975. Detection of carcinogens as mutagens in the Salmonella/ microsome test: Assay of 300 chemicals. Proc. Natl. Acad. Sci. USA 72:5135–5139.PubMedCrossRefGoogle Scholar
  16. 16.
    Sugimura, T., S. Sato, M. Nagao, T. Yahagi, T. Matsushima, Y. Seino, M. Takeuchi, and T. Kawachi. 1976. Overlapping of carcinogens and mutagens. In: Fundamentals in Cancer Prevention. P.N. Magee, S. Takayama, T. Sugimura, and T. Matshushima, eds. Univ. Tokyo Press: Tokyo/Univ.; Park Press: Baltimore, MD. pp. 191–215.Google Scholar
  17. 17.
    Lutz, W.K. 1979. In vivo covalent binding of organic chemicals to DNA as a quantitative indicator in the process of chemical carcinogenesis. Mutat. Res. 65:289–356.PubMedGoogle Scholar
  18. 18.
    Goth, R., and M.F. Rajewsky. 1974. Persistence of O 6-ethylguanine in rat-brain DNA: Correlation with nervous system-specific carcinogenesis by ethylnitrosourea. Proc. Natl. Acad. Sci. USA 71:639–643.PubMedCrossRefGoogle Scholar
  19. 19.
    Margison, G.P., and P. Kleihues. 1975. Chemical carcinogenesis in the nervous system. Preferential accumulation of O 4-methylguanine in rat brain deoxyribonucleic acid during repetitive administration of N-methyl-N-nitrosourea. Biochem. J. 148:521–525.PubMedGoogle Scholar
  20. 20.
    Cleaver, J.E. 1975. Methods for studying repair of DNA damaged by physical and chemical carcinogens. Meth. Cancer Res11:123–165.Google Scholar
  21. 21.
    Hanawalt, P.C., P.K. Cooper, A.K. Ganesan, and C.A. Smith. 1979. DNA repair in bacteria and mammalian cells. Ann. Rev. Biochem. 48:783–836.PubMedCrossRefGoogle Scholar
  22. 22.
    Lindahl, T. 1979. DNA glycosylases, endonucleases for apurinic/apyrimidinic sites, and base excision-repair. Prog. Nucl. Acid Res. Molec. Biol. 22:25–192.Google Scholar
  23. 23.
    Cairns, J. 1980. Bacteria as proper subjects for cancer research. Proc. R. Soc. Lond. B. 208:121–133.PubMedCrossRefGoogle Scholar
  24. 24.
    Olsson, M., and T. Lindahl. 1980. Repair of alkylated DNA in Escherichia coli. Methyl group transfer from Oh- methylguanine to a protein cysteine residue. J. Biol. Chem. 255:10569–10571.PubMedGoogle Scholar
  25. 25.
    Laval, J., J. Pierre, and F. Laval. 1981. Release of 7-methylguanine residues from alkylated DNA by extracts of Micrococcus luteus and Escherichia cola. Proc. Natl. Acad. Sci. USA 78:852–855.PubMedCrossRefGoogle Scholar
  26. 26.
    Singer, B., and T.P. Brent. 1981. Human lymphoblasts contain DNA glycosylase activity excising N-3 and N-7 methyl and ethyl purines but not O6-alkylguanines or 1-alkyladenines. Proc. Natl. Acad. Sci. USA 78:856–860.PubMedCrossRefGoogle Scholar
  27. 27.
    Margison, G.P., and A.E. Pegg. 1981. Enzymatic release of 7-methylguanine from methylated DNA by rodent liver extracts. Proc. Natl. Acad. Sci. USA 78:861–865.PubMedCrossRefGoogle Scholar
  28. 28.
    Sirover, M.A. 1979. Induction of the DNA repair enzyme uracil-DNA glycosylase in stimulated human lymphocytes. Cancer Res. 39:2090–2095.PubMedGoogle Scholar
  29. 29.
    Gupta, P.K., and M.A. Sirover. 1980. Sequential stimulation of DNA repair and DNA replication in normal human cells. Mutat. Res. 72:273–284.PubMedCrossRefGoogle Scholar
  30. 30.
    Gombar, C.T., E.J. Katz, P.N. Magee, and M.A. Sirover. 1981. Induction of the DNA repair enzymes uracil DNA glycosylase and 3-methyladenine DNA glycosylase in regenerating rat liver. Carcinogenesis 2:595–599.PubMedCrossRefGoogle Scholar
  31. 31.
    Craddock, V.M. 1976. Cell proliferation and experimental liver cancer. In: Liver Cell Cancer, Vol. 8. H.M. Cameron, D.A. Linsell, and G.P. Warwick, eds. Elsevier Publishing Company: Amsterdam, New York, and Oxford. pp. 153–201.Google Scholar
  32. 32.
    Kleihues, P., and G.P. Margison. 1976. Exhaustion and recovery of repair excision of 0 6-methylguanine from rat liver DNA. Nature 259:153–155.PubMedCrossRefGoogle Scholar
  33. 33.
    Rabes, H.M., R. Kerler, R. Wilhelm, G. Rode, and H. Riess. 1979. Alkylation of DNA and RNA by [1LC]dimethylnitrosamine in hydroxyurea-synchronized regenerating rat liver. Cancer Res. 39:4228–4236.PubMedGoogle Scholar
  34. 34.
    Smith, G.J., D.G. Kaufman, and J.W. Grisham. 1980. Decreased excision of O6-methylguanine and N7-methylguanine during the S phase in 10T1/2 cells. Biochem. Biophys. Res. Commun. 92:787–794.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • P. N. Magee
    • 1
  1. 1.Fels Research Institute and Department of PathologyTemple University School of MedicinePhiladelphiaUSA

Personalised recommendations