SOS Functions Induced in Carcinogen-Treated Mammalian Cells

  • Alain Sarasin
  • Mauro Mezzina

Abstract

It is now well established that treatment, which blocks semi-conservative DNA synthesis, induces in bacteria a series of pleiotropic effects called SOS functions [1–3]. The bacterial RecA protein, in the presence of single-strand DNA, displays a protease activity, which will specifically cleave its own repressor — the LexA protein — and the repressor of λ phage leading to prophage induction in a lysogenic bacteria. The cleavage of the LexA protein turns on several other genes which belong to the SOS response such as recA, umuC, sfiA, uvrA, uvrB genes (see Fig. 1). Among these responses, the umuC gene product seems to be partly responsible for the error-prone repair pathway expressed in treated-bacteria. Since SOS functions in bacteria are strongly mutagenic and can lead to virus induction, it is of great interest to determine if such functions could also be induced in mammalian cells treated with carcinogens. The expression of some specific mutations and/or the induction of some integrated viral genomes could very well represent one of the first steps in the initiation of carcinogenesis. In order to approach this problem, we have studied the properties of the DNA replication process in SOS conditions (i.e., in cells treated with chemical or physical carcinogens) trying to answer two specific questions: 1) Does an error-prone replication pathway exist in mammalian cells? 2) Are any specific replication enzymes induced in carcinogen-treated mammalian cells?

Keywords

Simian Virus Monkey Cell Monkey Kidney Cell Lytic Cycle LexA Protein 
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.
    E. M. Witkin, Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli, Bacteriol. Rev., 40: 869 (1976).PubMedGoogle Scholar
  2. 2.
    M. Radman, SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis, in: “Molecular Mechanism for Repair of DNA,” P. C. Hanawalt and R. B. Setlow, eds., Plenum Press, New York (1975).Google Scholar
  3. 3.
    R. Devoret, A. Goze, Y. Moulé, and A. Sarasin, Lysogenic induction and induced phage reactivation by aflatoxin Bi metabolites, in: “Mécanismes d’altération et de réparation du DNA: relation avec la mutagénèse et la cancérogénèse chimique,” R. Daudel, Y. Moulé, and F. Zajdela, eds., C.N.R.S., Paris (1977).Google Scholar
  4. 4.
    M. Defais, P. C. Hanawalt, and A. Sarasin, Viral probes for DNA repair, Adv. in Radiat. Biol., 10 (1982).Google Scholar
  5. 5.
    P. Caillet-Fauquet, M. Defais, and M. Radman, Molecular mechanism of induced mutagenesis, replication in vivo of bacteriophage ¢X174 single-stranded, ultraviolet light-irradiated DNA in intact and irradiated host cells, J. Mol. Biol., 117: 95 (1977).PubMedCrossRefGoogle Scholar
  6. 6.
    L. E. Bockstahler, and C. D. Lytle, Ultraviolet light enhanced reactivation of a mammalian virus, Biochem. Biophys. Res. Communn., 41: 184 (1970).CrossRefGoogle Scholar
  7. 7.
    L. E. Bockstahler and C. D. Lytle, Radiation enhanced reactivation of nuclear replicating mammalian viruses, Photochem. Photobiol., 25: 477 (1977).CrossRefGoogle Scholar
  8. 8.
    A. Sarasin and P. C. Hanawalt, Carcinogens enhance survival of UV-irradiated Simian Virus 40 in treated monkey kidney cells: Induction of a recovery pathway ? Proc. Natl. Acad. Sci. USA, 75: 346 (1978).PubMedCrossRefGoogle Scholar
  9. 9.
    A. Sarasin, Induced DNA repair processes in eucaryotic cells, Biochimie, 60: 1141 (1978).PubMedCrossRefGoogle Scholar
  10. 10.
    C. D. Lytle, Radiation-enhanced virus reactivation in mammalian cells, J. Natl. Cancer Instit. Monograph., 50: 145 (1978).Google Scholar
  11. 11.
    M. Günther, R. Wicker, S. Tiravy, and J. Coppey, Enhanced survival of ultraviolet-damaged parvovirus Lu III and Herpes virus in carcinogen pretreated transformed human cells, in: “Chromosome Damage and Repair,” E. Seeberg, ed., Plenum Press, New York (1981).Google Scholar
  12. 12.
    J. Rommelaere, J. M. Vos, J. J. Cornelis, and D. C. Ward, UV-enhanced reactivation of Minute-Virus-of-Mice: stimulation of a late step in the viral cycle, Photochem. Photobiol., 33: 845 (1981).CrossRefGoogle Scholar
  13. 13.
    C. D. Lytle, J. Coppey, and W. D. Taylor, Enhanced survival of ultraviolet-irradiated Herpes simplex virus in carcinogen-pretreated cells, Nature, 272: 60 (1978).PubMedCrossRefGoogle Scholar
  14. 14.
    S. M. D’Ambrosio and R. B. Setlow, Defective and enhanced post-replication repair in classical and variant Xeroderma pigmentosum cells treated with N-acetoxy-2-acetyl-aminofluorene, Cancer Res., 38: 1147 (1978).PubMedGoogle Scholar
  15. 15.
    J. Tooze, “DNA tumor viruses,” Cold Spring Harbor Laboratory, Cold Spring Harbor (1980).Google Scholar
  16. 16.
    P. Tegtmeyer and H. L. Ozer, Temperature-sensitive mutants of Simian virus 40: infection of permissive cells, J. Virol., 8: 516 (1971).PubMedGoogle Scholar
  17. 17.
    A. Sarasin, C. Gaillard, and A. Benoit, Molecular mechanism of error-prone DNA replication induced in UV-irradiated or acetoxyacetyl-aminofluorene treated monkey cells, J. Supramol. Struct. Cell. Biochem., 5: 203 (1981).Google Scholar
  18. 18.
    C. J. Lai and D. Nathans, A map of temperature-sensitive mutants of simian virus 40, Virology, 66: 70 (1975).PubMedCrossRefGoogle Scholar
  19. 19.
    P. Chambon, The molecular biology of the eukaryotic genome is coming of age, Cold Spring Harbor Quant. Biol., 42: 1209 (1977).CrossRefGoogle Scholar
  20. 20.
    A. Sarasin and A. Benoit, Induction of an error-prone mode of DNA repair of UV-irradiated monkey kidney cells, Mutation Res., 70: 71 (1980).PubMedCrossRefGoogle Scholar
  21. 21.
    A. Sarasin, C. Gaillard, and J. Feunteun, Induced mutagenesis of simian virus 40 in carcinogen-treated monkey cells, in: “Induced Mutagenesis: Molecular Mechanisms and their Implications for Environmental Protection,” C. W. Lawrence, L. Prakash, and F. Sherman, eds., Plenum Press, New York, in press.Google Scholar
  22. 22.
    D. Lackey, S. W. Krauss, and S. Linn, Isolation of an altered form of DNA polymerase I from Escherichia coai cells induced for recA/lexA functions, Proc. Natl. Acad. Sci. USA, 79: 330 (1982).PubMedCrossRefGoogle Scholar
  23. 23.
    S. Süderhäll and T. Lindhal, DNA ligases of eukaryotes, FEBS Lett., 67: 1 (1976).CrossRefGoogle Scholar
  24. 24.
    J. E. Cleaver, “Advances in Radiation Biology,” J. T. Lett, H. Adler, and M. Zeller, eds., Academic Press, New York (1974).Google Scholar
  25. 25.
    C. Pauling and L. Hiram, DNA ligase mutants of E. coli, Proc. Natl. Acad. Sci. USA, 60: 1595 (1967).Google Scholar
  26. 26.
    K. A. Nasmyth, Temperature-sensitive lethal mutants in the structural gene for DNA ligase in the yeast Schizosaccharomyces pombe, Cell, 12: 1109 (1977).PubMedCrossRefGoogle Scholar
  27. 27.
    S. Sderhäll, DNA ligases during rat liver regeneration, Nature, 260: 640 (1976).CrossRefGoogle Scholar
  28. 28.
    K. Tsukada, Changes in polynucleotide ligase during rat liver regeneration, Biochem. Biophys. Res. Commun., 57: 758 (1974).CrossRefGoogle Scholar
  29. 29.
    P. Beard, Polynucleotide ligase in mouse cells infected by polyoma virus, Biochim. Biophys. Acta, 269: 385 (1972).CrossRefGoogle Scholar
  30. 30.
    S. Spadari, Purification and properties of polynucleotide ligase in HeLa cells infected with Herpes simplex virus, Nucl. Acids Res., 3: 2155 (1976).CrossRefGoogle Scholar
  31. 31.
    S. Sóderhäll and T. Lindhal, Mammalian DNA ligases: serological evidence for two separate enzymes, J. Biol. Chem., 250: 8438 (1975).PubMedGoogle Scholar
  32. 32.
    M. Mezzina and S. Nocentini, DNA ligase activity in UV-irradiated monkey kidney cells, Nucl. Acids Res., 5: 4317 (1978).CrossRefGoogle Scholar
  33. 33.
    S. Nocentini and M. Mezzina, Effectsof ultraviolet irradiation of DNA ligase activity of human fibroblasts from normal and Xeroderma pigmentosum donors, in: “Chromosome Damage and Repair,” E. Seeberg, ed., Plenum Press, New York (1981).Google Scholar
  34. 34.
    R. Devoret, Bacterial tests for potential carcinogens, Scientific American, 241: 40 (1979).PubMedCrossRefGoogle Scholar
  35. 35.
    G. B. Zamansky, L. F. Kleinman, P. H. Black, and J. C. Kaplan, Reactivation of Herpes simplex virus in a cell line inducible for simian virus 40 synthesis, Mutation Res., 71: 1 (1980).CrossRefGoogle Scholar
  36. 36.
    L. E. Bockstahler, Induction and enhanced reactivation of mammalian viruses by light, Prog. Nucl. Acid Res. Mol. Biol., 26: 303 (1981).CrossRefGoogle Scholar
  37. 37.
    A. Gentil, Effects of tumor promoters on sister chromatid exchange, in: “Sister chromatid exchanges,” Alan R. Liss, New York, in press (1982).Google Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • Alain Sarasin
    • 1
  • Mauro Mezzina
    • 1
  1. 1.Institut de Recherches Scientifiques sur le CancerVillejuif CedexFrance

Personalised recommendations