Abstract
THE stability of binding of chemical carcinogens to DNA1–5, in vivo suggests a molecular mechanism for tumour initiation. This interaction may be mutagenic in that it may affect the accuracy with which the modified DNA is copied by cellular DNA polymerases. We now report that the modification of a synthetic polynucleotide template with β-propiolactone increases the incorporation of non-complementary base-paired nucleotides into DNA with the DNA polymerase from either avian myeloblastosis virus (AMV) or sea urchin embryos. Homogeneous AMV DNA polymerase and partially purified sea urchin nuclear DNA polymerase, which are devoid of nuclease activity6,7 were used. β-Propiolactone is a potent mutagen8,9 and carcinogen, initiating tumours in mice10, rats11 and hamsters12. It is an alkylating agent that reacts with guanine and adenine nucleotides in DNA13.
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
Epstein, S. M., Benedette, E. C., Shinozuka, M., Bartus, B., and Farber, E., Chem.-Biol. Int., 1, 113–124 (1969–1970).
Prakashi, L., and Strauss, B., J. Bact., 102, 760–766.
Szafarz, D., and Weisburger, J. H., Cancer Res., 29, 962–968 (1969).
Warwick, G. P., and Roberts, J. J., Nature, 213, 1206–1207 (1967).
Goth, R., and Pajewsky, M. F., Proc. natn. Acad. Sci. U.S.A., 71, 639–643 (1974).
Hurwitz, J., and Leis, J. P., J. Virol., 9, 116–129 (1972).
Fansler, B. S., and Loeb, L. A., in Methods in enzymology (edit. by Grossman, L., and Moldave, K.), 29, 53–69 (1974).
Fukuda, S., and Yamamoto, N., Cancer Res., 30, 830–833 (1970).
Van Durren, B. L., Ann. N.Y. Acad. Sci., 163, 633–651 (1969).
Roe, F. J. C., and Glendenning, O. M., Br. J. Cancer, 10, 357–362 (1956).
Searle, C. E., Br. J. Cancer, 15, 804–811 (1961).
Parish, D. J., and Searle, C. E., Br. J. Cancer, 20, 206–209 (1966).
Colburn, N. H., and Boutwell, R. K., Cancer Res., 28, 642–652 (1968).
Battula, N., and Loeb, L. A., J. biol. Chem., 249, 4086–4093 (1974).
Loeb, L. A., J. biol. Chem., 244, 1672–1681 (1969).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
SIROVER, M., LOEB, L. Erroneous base-pairing induced by a chemical carcinogen during DNA synthesis. Nature 252, 414–416 (1974). https://doi.org/10.1038/252414a0
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1038/252414a0
This article is cited by
-
Depurination decreases fidelity of DNA synthesis in vitro
Nature (1977)
-
The effect of nitrosoguanidine upon DNA synthesis in vitro
Molecular and General Genetics MGG (1976)
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.