Parvoviral Probe for Assessing the Mutagenic Risk of Low Doses of Radiation and Chemicals Administered to Human Cells

  • J. J. Cornelis
  • C. Dinsart
  • Z. Z. Su
  • J. Rommelaere


The marketing of an increasing number of chemicals makes it desirable to dispose of adequate tests for assessing their mutagenic/carcinogenic risk for man. The traditionally used animal tests are often long-lasting and very expensive, especially when the effect of low doses is sought. This led to the development of a battery of semi in vivo and in vitro tests using both prokaryotic and eukaryotic cells, which can be used routinely and serve as a guideline for the in vivo tests [1]. Cells collected from animals, including humans, can be cultured in vitro using appropriate nutritive media. Such cell cultures constitute a relatively well-defined system to analyze the toxic, mutagenic and transforming effect of exposure to environmental compounds. A widely used endpoint is the induction of chromatid and chromosome rearrangements. Visible karyotypic changes, however, do not necessarily accompany mutagenesis and do not provide an absolute indicator of the latter. Selective systems were thus developed, allowing the direct measurement of mutation induction in the genes of mammalian cells [2] or of viruses infecting those cells (see Introduction). The scope of this paper is to validate the use of the Hamster Osteolytic virus H-1, an autonomous parvovirus, for assessing the mutagenic risk associated with the exposure of human cells to low doses of radiations or chemicals.


Simian Virus Xeroderma Pigmentosum Genotoxic Agent Mutation Assay Cell Pretreatment 
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  1. 1.
    M. Hollstein and J. McCann, Short term tests for carcinogens and mutagens, Mutation Res., 65: 133 (1979).PubMedCrossRefGoogle Scholar
  2. 2.
    R. S. Gupta and L. Siminovitch, Genetic markers for quantitative mutagenesis studies in Chinese hamster ovary cells, Mutation Res., 69: 113 (1980).PubMedCrossRefGoogle Scholar
  3. 3.
    P. Tattersall and D. C. Ward, The parvoviruses: an introduction, in: “Replication of Mammalian Parvoviruses,” D. C. Ward and P. Tattersall, eds., p. 3 Cold Spring Harbor Laboratory, New York (1978).Google Scholar
  4. 4.
    S. L. Rhode, H-1 DNA synthesis, in: “Replication of Mammalian Parvoviruses,” D. C. Ward and P. Tattersall, eds., p. 279, Cold Spring Harbor Laboratory, New York (1978).Google Scholar
  5. 5.
    T. W. Glover, C. C. Chang, J. E. Trosko, and S. L. Li, Ultraviolet light induction of diphteria toxin-resistant mutants in normal and Xeroderma pigmentosum human fibroblasts, Proc. Natl. Acad. Sci. USA, 76: 3982 (1979).PubMedCrossRefGoogle Scholar
  6. 6.
    J. D. Hall and D. W. Mount, Mechanisms of DNA replication and mutagenesis in ultraviolet-irradiated bacteria and mammalian cells, Progress in Nucleic Acid Res., 25: 53 (1981).CrossRefGoogle Scholar
  7. 7.
    S. L. Rhode, Replication process of the parvovirus H-1, J. Virol., 17: 659 (1976).PubMedGoogle Scholar
  8. 8.
    J. W. Drake and R. H. Baltz, The biochemistry of mutagenesis, Ann. Rev. Biochem., 45: 11 (1976).PubMedCrossRefGoogle Scholar
  9. 9.
    B. A. Bridges, Ultraviolet light mutagenesis in bacteria: a result of the failure of normal error-correcting mechanisms?, in: “Progress in Environmental Mutagenesis,” M. Alacevic, ed., p. 131, Elsevier, Amsterdam (1980).Google Scholar
  10. 10.
    M. Radman, SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis, in: “Molecular Mechanisms for Repair of DNA,” P. C. Hanawalt and R. B. Setlow, eds., p. 355, Plenum, New York (1975).CrossRefGoogle Scholar
  11. 11.
    E. M. Witkin, Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli Bacteriol. Rev., 40: 869 (1976).PubMedGoogle Scholar
  12. 12.
    S. Gottesman, Genetic control of the SOS system in Escherichia coli Cell, 23: 1 (1981).Google Scholar
  13. 13.
    M. J. Defais, P. C. Hanawalt, and A. R. Sarasin, Viral probes for DNA repair, Adv. in Radiat. Biol., 10:in press (1981).Google Scholar
  14. 14.
    J. J. Weigle, Induction of mutations in a bacterial virus, Proc. Natl. Acad. Sci. USA, 39: 628 (1953).PubMedCrossRefGoogle Scholar
  15. 15.
    P. Caillet-Fauquet, M. J. Defais, and M. Radman, Molecular mechanisms 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
  16. 16.
    R. M. Schaaper and L. A. Loeb, Depurination causes mutations in SOS-induced cells, Proc. Natl. Acad. Sci. USA, 78: 1773 (1981).PubMedCrossRefGoogle Scholar
  17. 17.
    C. D. Lytle, Radiation-enhanced virus reactivation in mammalian cells, J. Natl. Cancer Inst. Monogr., 50: 145 (1978).Google Scholar
  18. 18.
    M. Radman, Is there SOS induction in mammalian cells?, Photochem. Photobiol., 32: 823 (1980).PubMedCrossRefGoogle Scholar
  19. 19.
    U. Das Gupta and W. C. Summers, Ultraviolet reactivation of herpes simplex virus is mutagenic and inducible in mammalian cells, Proc. Natl. Acad. Sci. USA, 75: 2378 (1978).CrossRefGoogle Scholar
  20. 20.
    C. D. Lytle, J. G. Goddard, and C. H. Lin, Repair and mutagenesis of herpes simplex virus in UV-irradiated monkey cells, Mutation Res., 70: 139 (1980).PubMedCrossRefGoogle Scholar
  21. 21.
    J. J. Cornelis, J. H. Lupker, and A. J. van der Eb, UV-reactivation, virus production and mutagenesis of SV40 in UV-irradiated monkey kidney cells, Mutation Res., 71: 139 (1980).PubMedCrossRefGoogle Scholar
  22. 22.
    J. J. Cornelis, J. H. Lupker, B. Klein, and A. J. van der Eb, The effect of cell irradiation on mutation in ultraviolet-irradiated and intact simian virus 40, Mutation Res., 82: 1 (1981).PubMedCrossRefGoogle Scholar
  23. 23.
    J. J. Cornelis, Z. Z. Su, D. C. Ward, and J. Rommelaere, Indirect induction of mutagenesis of intact parvovirus H-1 in mammalian cells treated with UV-light or with UV-irradiated H-1 or simian virus 40, Proc. Natl. Acad. Sci. USA, 78:in press (1981).Google Scholar
  24. 24.
    A. Sarasin and A. Benoit, Induction of an error-prone mode of DNA repair in UV-irradiated monkey kidney cells, Mutation Res., 70: 71 (1980).PubMedCrossRefGoogle Scholar
  25. 25.
    J. J. Cornelis, B. Klein, J. H. Lupker, P. J. Abrahams, R. A. M. Hooft van Huysduynen, and A. J. van der Eb, The use of viruses to study DNA repair and induced mutagenesis in mammalian cells, Progress in Mutation Res., 4:in press (1981).Google Scholar
  26. 26.
    Z. Z. Su, J. J. Cornelis, and J. Rommelaere, Mutagenesis of intact parvovirus H-1 is expressed coordinately with enhanced reactivation of ultraviolet irradiated virus in human and rat cells treated with 2-nitronaphthofurans, Carcinogenesis, 10: in press (1981).Google Scholar
  27. 27.
    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, ed., in press, Plenum, New York (1982).Google Scholar
  28. 28.
    R. S. Day and C. Ziolkowski, Studies on UV-induced viral reversion, Cockayne’s syndrome, and MNNG damage using adenovirus 5, in: “DNA Repair Mechanisms,” P. C. Hanawalt, E. C. Friedberg, and C. F. Fox, eds., p. 535, Academic Press, New York (1978).Google Scholar
  29. 29.
    N. Weill-Thevenet, J. P. Buisson, R. Royer, and M. Hofnung, Mutagenic activity of benzofurans and naphthofurans in the Salmonella/microsome assay: 2-nitro- 7-methoxy-naphtho (2.1-b) furan (R 7000), a new highly potent mutagenic agent, Mutation Res., 88: 355 (1981).PubMedCrossRefGoogle Scholar
  30. 30.
    J. Y. Chou and R. G. Martin, DNA infectivity and the induction of host DNA synthesis with temperature-sensitive mutants of simian virus 40, J. Virol., 15: 145 (1975).PubMedGoogle Scholar
  31. 31.
    J. Tooze, DNA Tumor Viruses, Part 2, Cold Spring Harbor Laboratory, New York (1980).Google Scholar
  32. 32.
    E. D. Sebring, T. J. Kelly, M. M. Thoren, and N. P. Salzman, Structure of replicating simian virus 40 deoxyribonucleic acid molecules, J. Virol., 8: 478 (1971).PubMedGoogle Scholar
  33. 33.
    B. Hirt, Selective extraction of polyoma DNA from infected mouse cell cultures, J. Mol. Biol., 26: 365 (1967).PubMedCrossRefGoogle Scholar
  34. 34.
    P. J. Abrahams and A. J. van der Eb, Host-cell reactivation of ultraviolet-irradiated SV40 DNA in five complementation groups of xeroderma pigmentosum, Mutation Res., 35: 13 (1976).PubMedCrossRefGoogle Scholar
  35. 35.
    F. L. Graham and A. J. van der Eb, A new technique for the assay of infectivity of human adenovirus 5 DNA, Virology, 52: 456 (1973).PubMedCrossRefGoogle Scholar
  36. 36.
    A. R. 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
  37. 37.
    S. Nocentini, J. Coppey, J. P. Buisson, and R. Royer, Inhibition of DNA synthesis in relation to induced herpes virus reactivation in monkey cells treated by a variety of 2-nitronaphthofurans, Mutation Res., in press (1981).Google Scholar
  38. 38.
    R. G. Martin and V. P. Setlow, The initiation of SV40 DNA synthesis is not unique to the replication origin, Cell, 20: 381 (1980).PubMedCrossRefGoogle Scholar
  39. 39.
    T. Lindahl and B. Nyberg, Rate of depurination of native deoxyribonucleic acid, Biochemistry, 11: 3610 (1972).PubMedCrossRefGoogle Scholar
  40. 40.
    J. M. Vos, J. J. Cornelis, S. Limbosch, F. Zampetti-Bosseler, and J. Rommelaere, UV-irradiation of related mouse hybrid cells: similar increase in capacity to replicate intact Minute-Virusof-Mice but differential enhancement of survival of UV-irradiated virus, Mutation Res., in press (1981).Google Scholar
  41. 41.
    R. M. Irbe, L. M. E. Morin, and M. Oishi, Prophage (c80) induction in Escherichia coli K-12 by specific deoxyoligonucleotides, Proc. Natl. Acad. Sci. USA, 78: 138 (1981).PubMedCrossRefGoogle Scholar
  42. 42.
    J. Coppey and S. Menezes, Enhanced reactivation of ultraviolet damaged herpes virus in ultraviolet pretreated skin fibroblasts of cancer prone donors, Carcinogenesis, in press (1981).Google Scholar
  43. 43.
    J. J. Mc Cormick and V. M. Maher, Mammalian cell mutagenesis as a biological consequence of DNA damage, in: “DNA Repair Mechanisms,” P. C. Hanawalt, E. C. Friedberg, and C. F. Fox, eds., p. 739, Academic Press, New York (1978).Google Scholar
  44. 44.
    C. C. Chang, S. M. D’Ambrosio, R. Schultz, J. E. Trosko, and R. B. Setlow, Modifications of UV-induced mutation frequencies in Chinese hamster cells by dose fractionation, cycloheximide and caffeine treatments, Mutation Res., 52: 231 (1978).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • J. J. Cornelis
    • 1
  • C. Dinsart
    • 1
  • Z. Z. Su
    • 1
  • J. Rommelaere
    • 1
  1. 1.Department of Molecular BiologyUniversité Libre de BruxellesRhode Saint GenèseBelgium

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