Differential growth inhibition by 5-fluorouracil in human colorectal carcinoma cell lines

E. Tokunaga, S. Oda, M. Fukushima, Yoshihiko Maehara, K. Sugimachi

Research output: Contribution to journalArticle

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Abstract

The effects of 5-fluorouracil (5-FU) on cell growth were investigated using a primary culture of human fibroblasts, MRC-5, and three established human colon cancer cell lines, DLD-1, LoVo and SW620. Detailed flow cytometric analyses revealed differential growth inhibition among these cell lines including three modes of cell growth modulation: (a) loss or accumulation of S phase cells; (b) G2/M block; and (c) G1-S arrest. From analyses on the amount of 5-FU incorporated into cellular RNA and the activity of thymidylate synthase (TS), suppression of TS and depletion of dTTP, a possible consequence of the former, was considered to be the major action of 5-FU in these cells. Differences in the cellular responses to the nucleotide pool imbalance appeared to make the cell growth modulation diverse. Loss of S phase cells and G1-S phase arrest were evident in p53 wild-type cells, MRC-5 and LoVo. Cells proficient in DNA mismatch repair, SW620 and MRC-5, showed marked modulations in S-G2/M progression. These findings suggest that multiple factors, including p53 and DNA mismatch repair, participate in diverse cell growth modulations in cells treated with 5-FU. Cellular resistance to 5-FU correlated well with a loss of modulations in S-G2/M progression, rather than with a defect of G1-S arrest, which suggests the significance of DNA mismatch repair as a factor affecting the sensitivity of cells to 5-FU. (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1998-2006
Number of pages9
JournalEuropean Journal of Cancer
Volume36
Issue number15
DOIs
Publication statusPublished - Oct 13 2000

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Fluorouracil
Colorectal Neoplasms
Cell Line
Growth
DNA Mismatch Repair
S Phase
Thymidylate Synthase
G1 Phase
Colonic Neoplasms
Nucleotides
Fibroblasts
RNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Differential growth inhibition by 5-fluorouracil in human colorectal carcinoma cell lines. / Tokunaga, E.; Oda, S.; Fukushima, M.; Maehara, Yoshihiko; Sugimachi, K.

In: European Journal of Cancer, Vol. 36, No. 15, 13.10.2000, p. 1998-2006.

Research output: Contribution to journalArticle

Tokunaga, E. ; Oda, S. ; Fukushima, M. ; Maehara, Yoshihiko ; Sugimachi, K. / Differential growth inhibition by 5-fluorouracil in human colorectal carcinoma cell lines. In: European Journal of Cancer. 2000 ; Vol. 36, No. 15. pp. 1998-2006.
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