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 Murgo, A. J. Articles by Clarkson, B. D. Search for Related Content PubMed PubMed Citation Articles by Murgo, A. J. Articles by Clarkson, B. D.

Effects of Thymidine and Thymidine Plus 5-Fluorouracil on the Growth Kinetics of a Human Lymphoid Cell Line¹

Laboratories of Hematopoietic Cell Kinetics [A. J. M., J. F., D. B., A. S., B. C.] and Clinical Pharmacology [T. W., K. L. V., C. W. Y.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021

We have studied the effects of thymidine (dThd) alone and in combination with 5-fluorouracil (FUra) on the survival and growth kinetics of a rapidly growing lymphoid cell line, SK-L7, in suspension culture. Continuous exposure to 10^-3 M dThd increased the doubling time from 14 hr in the untreated cultures to 24 hr and reduced the cloning efficiency by about 50% after 72 hr exposure. At a 10^-2 M concentration, dThd caused a progressive decline in trypan blue-excluding cells and a 98% reduction in the cloning efficiency by 72 hr, but failed to kill all the cells even after 6 days. Flow cytometric measurements of propidium iodide-stained cells showed a maximum accumulation of cells in S phase after 12 hr exposure, 74 and 85% with 10^-3 and 10^-2 M dThd, respectively, as compared to 61% in untreated cells. By 72 hr, the distribution of surviving cells through the cell cycle returned almost to the unperturbed state. dThd (10^-4 M) and thymine (10^-3 M) had no effect on the cell cycle or on growth rate. Continuous exposure to 5 x 10^-7 M FUra alone prolonged the doubling time to about 24 hr and caused a delay in S-phase progression. dThd did not potentiate the cytotoxic effects of FUra, and the combined effects of these two drugs were less than additive. dThd (10^-3 M) protected against the lethal effects of 5 x 10^-7 M FUra and prevented the S-phase accumulation that occurred with FUra alone. dThd caused a progressive decrease in the concentration of FUra in the media by promoting the conversion of FUra to 5-fluoro-2'-deoxyuridine.

¹ Supported in part by National Cancer Institute Grants CA-16757 and 19117, American Cancer Society Grant ACS-CH-6I, and the United Leukemia Fund. Presented in part at the American Association for Cancer Research Meeting, May 1979 (19).

² To whom requests for reprints should be addressed, at Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, N. Y. 10021.

Received 10/ 4/79. Accepted 2/ 7/80.

This article has been cited by other articles:

				P. A. Hill, A. Tumber, and M. C. Meikle Multiple Extracellular Signals Promote Osteoblast Survival and Apoptosis Endocrinology, September 1, 1997; 138(9): 3849 - 3858. [Abstract] [Full Text] [PDF]