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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Crick, F. H. C. Nature 227, 561–563 (1970).
Commoner, B. Nature 203, 486–491 (1964); 220, 334–340 (1968).
Auerbach, C. Mutation Research Problems, Results and Perspectives (Chapman and Hall, London, 1976).
Drake, J. W., Allen, E. F., Forsberg, S. A., Preparata, R. M. & Greening, E. O. Nature 221, 1128–1131 (1969).
Speyer, J. F., Karam, J. D. & Lenny, A. B. Cold Spring Harb. Symp. quant. Biol. 31, 693–699 (1966).
Kornberg, A. in DNA Synthesis 63, 88–94 (Freeman, San Francisco, 1974).
Peterson, A. R. et al. Mutat. Res. 36, 345–356 (1976).
Peterson, A. R., Peterson, H. & Heidelberger, C. Mutat. Res. 24, 25–33 (1974); 29, 127–137 (1975).
Benke, P. J., Herrick, N. & Herbert, A. J. clin. Invest. 52, 2234–2244 (1973).
DeMars, R. & Held, K. Humangenetik 16, 87–110 (1972).
Arlett, C. F., Turnbull, D., Harcourt, S. A., Lehmann, A. R. & Colella, C. M. Mutat. Res. 33, 261–278 (1975).
Davies, P. J. & Parry, J. Genet. Res. 24, 311–314 (1974).
Peterson, A. R., Bertram, J. S. & Heidelberger, C. Cancer Res. 34, 1592–1599 (1974).
Peterson, A. R., Peterson, H. & Heidelberger, C. Cancer Res. (in the press).
O'Neill, J. P., Brimer, P. A. Machanoff, R., Hirsch, G. P. & Hsie, A. W. Mutat. Res. 45, 91–101 (1977).
Fox, M. & McMillan, S. Studio Biophys. 61, 71–79 (1977).
Cleaver, J. E. Thymidine Metabolism and Cell Kinetics 93–94 (North-Holland, Amsterdam, 1967).
Bjursell, G. & Reichard, P. J. biol. Chem. 218, 3904–3909 (1973).
Loeb, L. A. et al. J. Toxic, env. Hlth 2, 1297–1304 (1977).
Radman, M. in Molecular Mechanisms for Repair of DNA, part B (eds Hanawalt, P. C. & Setlow, R. B.) 355–368 (Plenum, New York, 1975).
Bradley, M. O. & Sharkey, N. A. Nature 274, 607–608 (1978).
Bresler, S. E., Mosevitsky, M. I. & Vyacheslavov, L. G. Mutat. Res. 19, 281–293 (1973).
Smith, M. D., Green, R. R., Ripley, L. S. & Drake, J. W. Genetics 74, 393–403 (1973).
Barclay, B. J. & Little, J. G. Molec. gen. Genet. 160, 33–40 (1978).
Parker, J., Pollard, J. W. & Stanners, C. P. Proc. natn. Acad. Sci. U.S.A. 75, 1091–1095 (1978).
Bujard, H. & Heidelberger, C. Biochemistry 5, 3339–3345 (1966).
Orgel, L. E. Nature 243, 441–445 (1973).
Loeb, L. A., Sirover, M. A. & Agarwal, S. S. Adv. exp. Biol. Med. 91, 103–115 (1977).
Krahn, D. F. & Heidelberger, C. Mutat. Res. 46, 26–44 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/276508a0
This article is cited by
-
Analysis of bromodeoxyuridine-induced single and twin sister chromatid exchanges in tetraploid Chinese hamster ovary cells
Chromosoma (1986)
-
Abilities of wild-type and thymidine kinase-deficient Friend mouse erythroleukemia cells to undergo unscheduled DNA synthesis following mutagen treatment
Somatic Cell and Molecular Genetics (1986)
-
Evidence for indirect involvement of thymidine kinase in excision repair processes in mouse cell lines
Somatic Cell and Molecular Genetics (1985)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.