Effects of Various Promoters on Cell Transformation by Simian Virus 40 Mutants

  • L. Daya-Grosjean
  • R. Monier
  • A. Sarasin


It is widely admitted that tumor induction occurs through a multistep process, the two first steps of which should be initiation and promotion (see Berenblum, 1975). Most carcinogens interact directly or indirectly with DNA to give rise to lesions on DNA which generally need to be repaired in order to permit the cell survival (Miller, 1978). The relationships between DNA repair and carcinogenesis become evident when studying some human syndromes such as xeroderma pigmentosum (XP), where patients develop skin cancer with a very high incidence after exposure to sun-light (Cleaver, 1968). The cells isolated from XP patients are unable to repair in vitro the DNA lesions, essentially pyrimidine dimers, made by UV-light. This result clearly indicates that unrepaired DNA lesions represent one of the first steps of carcinogenesis probably by giving rise to mutations due to incorrect base-pairing with the damaged base. Another way to get mutations is to use an error-prone repair pathway to repair lesions on DNA. Such an error-prone repair process has been well established in bacteria where it has been called the SOS repair pathway (Radman, 1975; Witkin, 1976; Devoret et al., 1977). Treatment of bacteria by various physical or chemical carcinogens, which inhibit DNA replication, induces the SOS repair pathway which will repair DNA lesions more efficiently but with a high rate of errors (Sarasin et al., 1977).


Soft Agar Tumor Promoter Simian Virus Xeroderma Pigmentosum Xeroderma Pigmentosum Patient 


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  1. Berenblum, I., The probable nature of promoting action and its significance in the understanding of the mechanism of carcino-genesis, Cancer Res., 14: 471 (1954).PubMedGoogle Scholar
  2. Berenblum, I., Origin of the concept of sequential stages of skin carcinogenesis, in: “Cancer: A comprehensive treatise,” Becker, ed., Plenum Press, New York (1975).Google Scholar
  3. Casto, B. C., Pieczynski, W. J., Janowsko, N., and Di Paolo, J. A., Significance of treatment interval and DNA repair in the enhancement of viral transformation by chemical carcinogens and mutagens, Chem. Biol. Interactions, 13: 105 (1976).CrossRefGoogle Scholar
  4. Cleaver, J. E., Defective repair replication of DNA in Xeroderma pigmentosum, Nature, 218: 652 (1968).PubMedCrossRefGoogle Scholar
  5. Devoret, R., Goze, A. Moulé, Y., and Sarasin, A., Lysogenic induction and induced phage reactivation by aflatoxin B1 metabolites, in: “Mécanismes d’alteration et de réparation du DNA: relation avec la mutagénèse et al cancérogénèse chimique,” R.Google Scholar
  6. Daudel, Y. Moulé, F. Zajdela, eds., C.N.R.S., Paris (1977).Google Scholar
  7. Diamond, L., Knorr, R., and Shimizu, Y., Enhancement of simian virus 40-induced transformation of Chinese hamster embryo cells by 4-nitroquinolíne-l-oxide, Cancer Res., 34: 2599 (1974).PubMedGoogle Scholar
  8. Diamond, L., O’Brien, T. G., and Baird, W. B., Tumor promoters and the mechanism of tumor promotion, Adv. Cancer Res., 32: 1 (1980).CrossRefGoogle Scholar
  9. Feunteun, J., Kress, M., Gardes, M., and Monier, R., Viable deletion mutants in the simian virus 40 early region, Proc. Natl. Acad. Sci. USA, 75: 4455 (1978).PubMedCrossRefGoogle Scholar
  10. Fisher, P. B., Bozzone, J. H., and Weinstein, I. B., Tumor promoters and epidermal growth factor stimulate anchorage-independent growth of adenovirus transformed rat embryo cells, Cell, 18: 695 (1979a).PubMedCrossRefGoogle Scholar
  11. Fisher, P. B., Dorsch-Häsler, K., Weinstein, I. B., and Ginsberg, H. S., Tumor promoters enhance anchorage-independent growth of adenovirus-transformed cells without altering the integration pattern of viral sequences, Nature, 281: 591 (1979b).PubMedCrossRefGoogle Scholar
  12. Fisher, P. B., Weinstein, I. B., Eisenberg, D., and Ginsberg, H. S., Interactions between adenovirus, a tumor promoter, and chemical carcinogens in transformation of rat embryo cell cultures, Proc. Natl. Acad. Sci. USA, 75: 2311 (1978).PubMedCrossRefGoogle Scholar
  13. Fluck, M. M., and Benjamin, T., Comparisons of two early gene functions essential for transformation in polyoma virus and SV40, Virology, 96: 205 (1979).PubMedCrossRefGoogle Scholar
  14. Hecker, E., Isolation and characterization of the co-carcinogenic principles from croton oil, Meth. Cancer Res., 6: 439 (1971).Google Scholar
  15. Heidelberger, C., Mondai, S., and Peterson, A. R., Initiation and promotion in cell cultures, in: “Mechanisms of tumor promotion and cocarcinogenesis,” T. Slaga, A. Sivak, R. Boutwell, eds., Raven Press, New York (1978)Google Scholar
  16. Hirai, K., Defendi, V., and Diamond, L., Enhancement of simian virus 40 transformation and integration by 4-nitroquinoline-l-oxide, Cancer Res., 34: 3497 (1974).PubMedGoogle Scholar
  17. Hynes, R. O., Alteration of cell-surface proteins by viral transformation and by proteolysis, Proc. Natl. Acad. Sci. USA, 70: 3170 (1973).PubMedCrossRefGoogle Scholar
  18. Kennedy, A. R., Mondai, S., Heidelberger, C., and Little, J. B., Enhancement of x-radiation transformation by a phorbol ester using C3H 10 T 1/2 cl 8 mouse embryo fibroblasts, Cancer Res., 38: 439 (1978).PubMedGoogle Scholar
  19. Kinsella, A. R., and Radman, M., Tumor promoter induces sister chromatid exchanges: relevance to mechanisms of carcinogenesis, Proc. Natl. Acad. Sci. USA, 75: 6149 (1978).PubMedCrossRefGoogle Scholar
  20. Lasne, C., Gentil, A., and Chouroulinkov, I., Two-stage malignant transformation of rat fibroblasts in tissue culture, Nature, 247: 490 (1974).PubMedCrossRefGoogle Scholar
  21. MacPherson, I., and Montagnier, L., Agar suspension culture for the selective assay of cells transformed by polyoma virus, Virology, 23: 291 (1964).PubMedCrossRefGoogle Scholar
  22. May, E., Kress, M., Daya-Grosjean, L., Monier, R., and May, P., Mapping of the viral mRNA encoding a super-T antigen of 115,000 daltons expressed in simian virus 40-transformed rat cell lines, J. Virol., 37: 24 (1981).PubMedGoogle Scholar
  23. Miller, E. C., Some current perspectives on chemical carcinogenesis in humans and experimental animals, Cancer Res., 38: 1479 (1978).PubMedGoogle Scholar
  24. Pollack, R., Osborn, M., and Weber, K., Patterns of organization of Actin and Myosin in normal and transformed cultured cells, Proc. Natl. Acad. Sci. USA, 72: 994 (1975).CrossRefGoogle Scholar
  25. Pollack, R., Risser, R., Conlon, S., and Rifkin, D., Plasminogen activator production accompanies loss of anchorage regulation in transformation of primary rat embryo cells by simian virus 40, Proc. Natl. Acad. Sci. USA, 71: 4792 (1974).PubMedCrossRefGoogle Scholar
  26. Radman, M., SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis, in: “Molecular Mechanism for Repair of DNA,” P. C. Hanawalt, R. B. Setlow, eds., Plenum Press, New York (1975).Google Scholar
  27. Reznikoff, C. A., Bronkow, D. W., and Heidelberger, C., Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of cell division, Cancer Res., 33: 3231 (1973).PubMedGoogle Scholar
  28. Sarasin, A., and Benoit, A., Induction of an error-prone mode of DNA repair in UV-irradiated monkey kidney cells, Mutation Res., 70: 71 (1980).PubMedCrossRefGoogle Scholar
  29. Sarasin, A., and Hanawalt, P. C., 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
  30. Sarasin, A., Goze, A., Devoret, R., and Moulé, Y., Induced reactivation of UV-damaged phage A in E. coli K12 host cells treated with aflatoxin B1 metabolites, Mutation Res., 42: 205 (1977).PubMedCrossRefGoogle Scholar
  31. Seif, R., Factors which disorganize microtubules of microfilaments increase the frequency of cell transformation by polyoma virua, J. Virol., 36: 421 (1980).PubMedGoogle Scholar
  32. Shenk, T. E., Carbon, J., and Berg, P., Construction of analysis of viable deletion mutants of simian virus 40, J. Virol., 18: 664 (1976).PubMedGoogle Scholar
  33. Sivak, A., and Van Duuren, B. L., Phenotypic expression of transformation: induction in cell culture by a phorbol ester, Science, 157: 1443 (1967).PubMedCrossRefGoogle Scholar
  34. Sleigh, M. J., Topp, W. C., Hanich, R., and Sambrook, J. F., Mutants of SV40 with an altered small t protein are reduced in their ability to transform cells, Cell, 14: 79 (1978).PubMedCrossRefGoogle Scholar
  35. Southern, G., Detection of specific sequences among DNA fragments separated by gel electrophoresis, J. Mol. Biol., 98: 503 (1975).PubMedCrossRefGoogle Scholar
  36. Tegtmeyer, P., Simian virus 40 DNA synthesis: the viral replicon, J. Virol., 10: 591 (1972).PubMedGoogle Scholar
  37. Tooze, J., “DNA tumor viruses, molecular biology of tumor viruses (Part II),” Cold Spring Harbor Laboratory (1980).Google Scholar
  38. Trosko, E., Dawson, B., Yotti, L. P., and Chang, C. C., Saccharin may act as a tumor promoter by inhibiting metabolic cooperation between cells, Nature, 285: 109 (1980).PubMedCrossRefGoogle Scholar
  39. Vlodaysky, I., Inbar, M., and Sachs, L., Membrane changes and adenosine triphosphate content in normal and malignant transformed cells, Proc. Natl. Acad. Sci. USA, 70: 1780 (1973).CrossRefGoogle Scholar
  40. Witkin, E. M., Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli, Bacteriol. Res., 40: 869 (1976).Google Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • L. Daya-Grosjean
    • 1
  • R. Monier
    • 1
  • A. Sarasin
    • 1
  1. 1.Laboratoire de Chimie des Acides NucléiquesInstiut de Recherches Scientifiques sur le Cancer CNRSVillejuif CedexFrance

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