Letter | Published:

Mutagenicity of thymidine to cultured Chinese hamster cells

Naturevolume 274pages607608 (1978) | Download Citation

Subjects

Abstract

THYMIDINE starvation is known to be both toxic and mutagenic to various prokaryotes, including Escherichia coli1,2, Bacillus subtilis3 and bacteriophage T4 (refs 4–6). Base excess, as well as base starvation, can also be mutagenic. For instance, Bernstein et al.5 showed that a superabundance of exogenous thymidine (4 mM) produced an increased reversion rate for some T4 amber mutants. In mammalian cells a superabundance of exogenous thymidine is toxic, perhaps by inhibiting DNA synthesis7–9. The mechanism for these effects may be related to the observations that dTTP inhibits the enzymatic reduction of CDP to dCDP by ribonucleoside diphosphate reductase10 and also that thymidine reduces the dCTP pools of Chinese hamster cells to 90% of normal11. We report here that a superabundance of exogenous thymidine is both toxic and highly mutagenic to V-79 Chinese hamster cells but that hydroxyurea, an inhibitor of ribonucleoside diphosphate reductase, is toxic but not mutagenic.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Coughlin, C. A. & Adelberg, E. A. Nature 178, 531–532 (1956).

  2. 2

    Weinberg, R. & Latham, A. B. J. Bact. 72, 570–572 (1956).

  3. 3

    Bresler, S., Mosevitsky, M. & Vyacheslavov, L. Nature 225, 764–766 (1970).

  4. 4

    Drake, J. W. & Greening, E. O. Proc. natn. Acad. Sci. U.S.A. 66, 823–829 (1970).

  5. 5

    Bernstein, C., Bernstein, H., Mufti, S. & Strom, B. Mutat. Res. 16, 113–119 (1972).

  6. 6

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

  7. 7

    Hakala, M. T. & Taylor, E. J. biol. Chem. 234, 126–128 (1959).

  8. 8

    Klenow, H. Biochim. biophys. Acta 35, 412–421 (1959).

  9. 9

    Morris, N. R. & Fischer, G. A. Biochim. Biophys. Acta 68, 84–92 (1963).

  10. 10

    Reichard, P., Canellakis, Z. N. & Canellakis, E. S. J. biol. Chem. 236, 2514–2519 (1961).

  11. 11

    Bjursell, G. & Reichard, P. J. biol. Chem. 248, 3904–3909 (1973).

  12. 12

    Bradley, M. O. & Sharkey, N. A. Nature 266, 724–726 (1977).

  13. 13

    Skoog, L. & Bjursell, G. J. biol. Chem. 249, 6434–6438 (1974).

  14. 14

    Walters, R. A., Tobey, R. A. & Ratliff, R. L. Biochim. biophys. Acta 319, 336–347 (1973).

Download references

Author information

Affiliations

  1. Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20014

    • MATTHEWS O. BRADLEY
    •  & NANCY A. SHARKEY

Authors

  1. Search for MATTHEWS O. BRADLEY in:

  2. Search for NANCY A. SHARKEY in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/274607a0

Further reading

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.