SOS Functions Induced in Carcinogen-Treated Mammalian Cells
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?
KeywordsSimian Virus Monkey Cell Monkey Kidney Cell Lytic Cycle LexA Protein
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- 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.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.M. Defais, P. C. Hanawalt, and A. Sarasin, Viral probes for DNA repair, Adv. in Radiat. Biol., 10 (1982).Google Scholar
- 10.C. D. Lytle, Radiation-enhanced virus reactivation in mammalian cells, J. Natl. Cancer Instit. Monograph., 50: 145 (1978).Google Scholar
- 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
- 15.J. Tooze, “DNA tumor viruses,” Cold Spring Harbor Laboratory, Cold Spring Harbor (1980).Google Scholar
- 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
- 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
- 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.C. Pauling and L. Hiram, DNA ligase mutants of E. coli, Proc. Natl. Acad. Sci. USA, 60: 1595 (1967).Google Scholar
- 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
- 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