This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lönn, U. Articles by Lönn, S. Search for Related Content PubMed PubMed Citation Articles by Lönn, U. Articles by Lönn, S.

DNA Lesions in Human Neoplastic Cells and Cytotoxicity of 5-Fluoropyrimidines¹

Radiumhemmet, Karolinska Hospital, and Department of Histology, Karolinska Institutet, S-104 01 Stockholm, Sweden

We have examined the induction of alkali-labile regions in DNA of human neoplastic cells treated with 5-fluorouracil and 5-fluorodeoxyuridine. 5-Fluorouracil induces DNA lesions by two mechanisms: incorporation of drug into DNA and a second mechanism not involving the incorporation. The second mechanism is seen in cells treated with aphidicolin, a specific inhibitor of DNA polymerase , to stop the movement of the DNA replication forks. 5-Fluorodeoxyuridine is not incorporated into DNA of these cells; only the second mechanism of induction of alkali-labile DNA is detected. The second mechanism is in all probability due to inefficient DNA repair of normally occurring defects in purine and pyrimidine residues. Furthermore there is a correlation between increasing levels of alkali-labile regions in the DNA and cytotoxicity of the drugs. This may be one explanation for the cytocidal effects of 5-fluoropyrimidines.

¹ This work was supported by grants from the Stockholm Cancer Society, Åhlens Foundation, and Karolinska Institutet.

² To whom requests for reprints should be addressed, at Radiumhemmet, Karolinska Hospital, P. O. Box 60 500, S-104 01 Stockholm, Sweden.

Received 1/14/86. Revised 4/ 1/86. Accepted 4/22/86.

This article has been cited by other articles:

				J. M. Carethers Review: Systemic treatment of advanced colorectal cancer: Tailoring therapy to the tumor Therapeutic Advances in Gastroenterology, July 1, 2008; 1(1): 33 - 42. [Abstract] [PDF]

				P. Noordhuis, U. Holwerda, C. L. Van der Wilt, C. J. Van Groeningen, K. Smid, S. Meijer, H. M. Pinedo, and G. J. Peters 5-Fluorouracil incorporation into RNA and DNA in relation to thymidylate synthase inhibition of human colorectal cancers Ann. Onc., July 1, 2004; 15(7): 1025 - 1032. [Abstract] [Full Text] [PDF]

				M. Meyers, M. W. Wagner, H.-S. Hwang, T. J. Kinsella, and D. A. Boothman Role of the hMLH1 DNA Mismatch Repair Protein in Fluoropyrimidine-mediated Cell Death and Cell Cycle Responses Cancer Res., July 1, 2001; 61(13): 5193 - 5201. [Abstract] [Full Text] [PDF]