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Schedule-dependent enhancement of 1-beta-D-arabinofuranosylcytosine incorporation into HL-60 DNA by deoxyguanosine.

Publication ,  Journal Article
Ross, DD; Akman, SA; Joneckis, CC; Yang, E; Bachur, NR
Published in: Cancer Res
April 1984

We studied the ability of the purine deoxynucleoside deoxyguanosine (dGuo) to enhance 1-beta-D-arabinofuranosylcytosine (ara-C) incorporation into DNA of HL-60 cultured human leukemia cells. The effects of dGuo on ara-C incorporation into DNA were compared to those of thymidine (dThd), a pyrimidine deoxynucleoside known to augment ara-C effects both in vitro and in vivo. Both deoxynucleosides doubled the cells in the S phase of the cell cycle within the exposure periods (up to 48 hr) and concentrations (10 to 1000 microM) tested. Both deoxynucleosides enhanced ara-C incorporation into DNA equally. However, dThd and dGuo differed in the schedule required to achieve this effect. Simultaneous exposure of cells to ara-C and dThd increased ara-C incorporation into DNA approximately 3.5-fold. Preincubation of cells with dThd for 16 hr prior to the addition of ara-C further enhanced ara-C incorporation into DNA (to approximately 5-fold) in direct proportion to the dThd-induced increase in cells in S phase. Preincubation was essential for dGuo, since 16-hr preincubation of cells with concentrations as low as 30 microM caused augmentation of ara-C incorporation into DNA; but simultaneous exposure of cells to dGuo and ara-C caused no augmentation of ara-C incorporation into DNA. The augmentation of ara-C incorporation into DNA caused by preincubation of the cells with dGuo results from a number of factors, including the cytokinetic effect of increasing the percentage of cells in S phase and the reduction of intracellular dCTP pools. Maximal dGuo enhancement of ara-C incorporation into DNA (approximately 5-fold) required greater than 100 microM dGuo, 16-hr preincubation with dGuo, and final incubation of cells with ara-C after removal of dGuo. We explain this further augmentation of ara-C incorporation into DNA caused by the removal of dGuo prior to adding ara-C by our observed inhibition of ara-C phosphorylation by dGuo concentrations greater than 100 microM.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 1984

Volume

44

Issue

4

Start / End Page

1530 / 1535

Location

United States

Related Subject Headings

  • Tritium
  • Thymidine
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Leukemia, Lymphoid
  • Kinetics
  • Humans
  • Flow Cytometry
  • Deoxyguanosine
  • DNA Replication
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ross, D. D., Akman, S. A., Joneckis, C. C., Yang, E., & Bachur, N. R. (1984). Schedule-dependent enhancement of 1-beta-D-arabinofuranosylcytosine incorporation into HL-60 DNA by deoxyguanosine. Cancer Res, 44(4), 1530–1535.
Ross, D. D., S. A. Akman, C. C. Joneckis, E. Yang, and N. R. Bachur. “Schedule-dependent enhancement of 1-beta-D-arabinofuranosylcytosine incorporation into HL-60 DNA by deoxyguanosine.Cancer Res 44, no. 4 (April 1984): 1530–35.
Ross DD, Akman SA, Joneckis CC, Yang E, Bachur NR. Schedule-dependent enhancement of 1-beta-D-arabinofuranosylcytosine incorporation into HL-60 DNA by deoxyguanosine. Cancer Res. 1984 Apr;44(4):1530–5.
Ross, D. D., et al. “Schedule-dependent enhancement of 1-beta-D-arabinofuranosylcytosine incorporation into HL-60 DNA by deoxyguanosine.Cancer Res, vol. 44, no. 4, Apr. 1984, pp. 1530–35.
Ross DD, Akman SA, Joneckis CC, Yang E, Bachur NR. Schedule-dependent enhancement of 1-beta-D-arabinofuranosylcytosine incorporation into HL-60 DNA by deoxyguanosine. Cancer Res. 1984 Apr;44(4):1530–1535.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 1984

Volume

44

Issue

4

Start / End Page

1530 / 1535

Location

United States

Related Subject Headings

  • Tritium
  • Thymidine
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Leukemia, Lymphoid
  • Kinetics
  • Humans
  • Flow Cytometry
  • Deoxyguanosine
  • DNA Replication