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Mutagenesis of Chinese hamster cells is facilitated by thymidine and deoxycytidine

Abstract

ONE-WAY information transfer from nucleic acids to proteins is generally considered to ensure accurate cell self-duplication, in which errors occur by mutation1. However, it has been argued that self-duplication is a multimolecular process consisting of several potentially error-prone stages2, and that mutation is a complex cellular process3. Moreover, it has been shown that error-prone DNA polymerases cause mutations in bacterio-phage T4 (ref. 4.5). We now report that mutations produced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), at two separate loci in Chinese hamster cells, are increased 3–10-fold when the cells are treated in the presence of low concentrations (2×10−5M) of thymidine (TdR) and deoxycytidine (GdR). We conclude that imbalanced nucleotide pools facilitate errors of replication of methylated DNA, and suggest that aberrant synthesis of macromolecules, facilitated by imbalances in precursor pools, plays an important part in the expression of genetic damage.

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References

  1. Crick, F. H. C. Nature 227, 561–563 (1970).

    Article  ADS  CAS  Google Scholar 

  2. Commoner, B. Nature 203, 486–491 (1964); 220, 334–340 (1968).

    Article  ADS  CAS  Google Scholar 

  3. Auerbach, C. Mutation Research Problems, Results and Perspectives (Chapman and Hall, London, 1976).

    Google Scholar 

  4. Drake, J. W., Allen, E. F., Forsberg, S. A., Preparata, R. M. & Greening, E. O. Nature 221, 1128–1131 (1969).

    Article  ADS  CAS  Google Scholar 

  5. Speyer, J. F., Karam, J. D. & Lenny, A. B. Cold Spring Harb. Symp. quant. Biol. 31, 693–699 (1966).

    Article  CAS  Google Scholar 

  6. Kornberg, A. in DNA Synthesis 63, 88–94 (Freeman, San Francisco, 1974).

    Google Scholar 

  7. Peterson, A. R. et al. Mutat. Res. 36, 345–356 (1976).

    Article  CAS  Google Scholar 

  8. Peterson, A. R., Peterson, H. & Heidelberger, C. Mutat. Res. 24, 25–33 (1974); 29, 127–137 (1975).

    Article  CAS  Google Scholar 

  9. Benke, P. J., Herrick, N. & Herbert, A. J. clin. Invest. 52, 2234–2244 (1973).

    Article  CAS  Google Scholar 

  10. DeMars, R. & Held, K. Humangenetik 16, 87–110 (1972).

    Article  CAS  Google Scholar 

  11. Arlett, C. F., Turnbull, D., Harcourt, S. A., Lehmann, A. R. & Colella, C. M. Mutat. Res. 33, 261–278 (1975).

    Article  CAS  Google Scholar 

  12. Davies, P. J. & Parry, J. Genet. Res. 24, 311–314 (1974).

    Article  CAS  Google Scholar 

  13. Peterson, A. R., Bertram, J. S. & Heidelberger, C. Cancer Res. 34, 1592–1599 (1974).

    CAS  PubMed  Google Scholar 

  14. Peterson, A. R., Peterson, H. & Heidelberger, C. Cancer Res. (in the press).

  15. O'Neill, J. P., Brimer, P. A. Machanoff, R., Hirsch, G. P. & Hsie, A. W. Mutat. Res. 45, 91–101 (1977).

    Article  CAS  Google Scholar 

  16. Fox, M. & McMillan, S. Studio Biophys. 61, 71–79 (1977).

    CAS  Google Scholar 

  17. Cleaver, J. E. Thymidine Metabolism and Cell Kinetics 93–94 (North-Holland, Amsterdam, 1967).

    Google Scholar 

  18. Bjursell, G. & Reichard, P. J. biol. Chem. 218, 3904–3909 (1973).

    Google Scholar 

  19. Loeb, L. A. et al. J. Toxic, env. Hlth 2, 1297–1304 (1977).

    Article  CAS  Google Scholar 

  20. Radman, M. in Molecular Mechanisms for Repair of DNA, part B (eds Hanawalt, P. C. & Setlow, R. B.) 355–368 (Plenum, New York, 1975).

    Book  Google Scholar 

  21. Bradley, M. O. & Sharkey, N. A. Nature 274, 607–608 (1978).

    Article  ADS  CAS  Google Scholar 

  22. Bresler, S. E., Mosevitsky, M. I. & Vyacheslavov, L. G. Mutat. Res. 19, 281–293 (1973).

    Article  CAS  Google Scholar 

  23. Smith, M. D., Green, R. R., Ripley, L. S. & Drake, J. W. Genetics 74, 393–403 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Barclay, B. J. & Little, J. G. Molec. gen. Genet. 160, 33–40 (1978).

    CAS  PubMed  Google Scholar 

  25. Parker, J., Pollard, J. W. & Stanners, C. P. Proc. natn. Acad. Sci. U.S.A. 75, 1091–1095 (1978).

    Article  ADS  CAS  Google Scholar 

  26. Bujard, H. & Heidelberger, C. Biochemistry 5, 3339–3345 (1966).

    Article  CAS  Google Scholar 

  27. Orgel, L. E. Nature 243, 441–445 (1973).

    Article  ADS  CAS  Google Scholar 

  28. Loeb, L. A., Sirover, M. A. & Agarwal, S. S. Adv. exp. Biol. Med. 91, 103–115 (1977).

    Article  CAS  Google Scholar 

  29. Krahn, D. F. & Heidelberger, C. Mutat. Res. 46, 26–44 (1977).

    Google Scholar 

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PETERSON, A., LANDOLPH, J., PETERSON, H. et al. Mutagenesis of Chinese hamster cells is facilitated by thymidine and deoxycytidine. Nature 276, 508–510 (1978). https://doi.org/10.1038/276508a0

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