Differential effects of gemcitabine on ribonucleotide pools of twenty-one solid tumour and leukaemia cell lines

Catharina J A Van Moorsel, Andries M. Bergman, Gijsbert Veerman, Daphne A. Voorn, Veronique W T Ruiz Van Haperen, Judith R. Kroep, Herbert M. Pinedo, Godefridus J. Peters

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


To gain a more detailed insight into the metabolism of 2',2'-difluoro-2'-deoxycytidine (dFdC, gemcitabine, Gemzar) and its effect on normal ribonucleotide (NTP) metabolism in relation to sensitivity, we studied the accumulation of dFdCTP and the changes in NTP pools after dFdC exposure in a panel of 21 solid tumour and leukaemia cell lines. Both sensitivity to dFdC and accumulation of dFdCTP were clearly cell line-dependent: in this panel of cell lines, the head and neck cancer (HNSCC) cell line 22B appeared to be the most sensitive, whereas the small cell lung cancer (SCLC) cell lines were the least sensitive to dFdC. The human leukaemia cell line CCRF-CEM accumulated the highest concentration of dFdCTP, whereas the non-SCLC cell lines accumulated the least. Not only the amount of dFdCTP accumulation was clearly related to the sensitivity for dFdC (R=-0.61), but also the intrinsic CTP/UTP ratio (R=0.97). NTP pools were affected considerably by dFdC treatment: in seven cell lines dFdC resulted in a 1.7-fold depletion of CTP pools, in two cell lines CTP pools were unaffected, but in 12 cell lines CTP pools increased about 2-fold. Furthermore, a 1.6-1.9-fold rise in ATP, UTP and GTP pools was shown in 20, 19 and 20 out of 21 cell lines, respectively. Only the UTP levels after treatment with dFdC were clearly related to the amount of dFdCTP accumulating in the cell (R=0.64 (P

Original languageEnglish (US)
Pages (from-to)5-12
Number of pages8
JournalBiochimica et Biophysica Acta - General Subjects
Issue number1
StatePublished - Mar 6 2000
Externally publishedYes


  • dFdCTP accumulation
  • Gemcitabine sensitivity
  • Ribonucleotide pool

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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