Effects of thymidine and thymidine plus 5-fluorouracil on the growth kinetics of a human lymphoid cell line
Murgo, A.J.; Fried, J.; Burchenal, D.; Vale, K.L.; Strife, A.; Woodcock, T.; Young, C.W.; Clarkson, B.D.
Cancer Research 40(5): 1543-1549
1980
ISSN/ISBN: 0008-5472 PMID: 6445227 Document Number: 156963
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 were studied. Continuous exposure to 10-3 M dThd increased the doubling time from 14 h in the untreated cultures to 24 h and reduced the cloning efficiency by about 50% after 72 h 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 h, 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 h exposure, 74 and 85% with 10-3 and 10-2 M dThd, respectively, as compared to 61% in untreated cells. By 72 h, 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 .times. 10-7 M FUra alone prolonged the doubling time to about 24 h and caused a delay in S-phase progression. dThd did not potentiate the cytotoxic effects of FUra, and the combined effects of these 2 drugs were less than additive. dThd (10-3 M) protected against the lethal effects of 5 .times. 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.