Modulation of 6-thioguanine activity by guanine in human promyelocytic leukemia HL-60 cells

H. W. Cheng, R. D. Armstrong, W. Sadee

Research output: Contribution to journalArticle

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Abstract

The effects of guanine co-administration on the metabolism and biological activity of 6-thioguanine (6-TG) were studied in human promyelocytic leukemia cells (HL-60). Cell growth, cytotoxicity (cloning assay), and cell differentiation were measured, along with nucleotide metabolism. Guanine was efficiently salvaged by HL-60 cells; at 200 μM, guanine suppressed the formation of 6-TG mononucleotides and abolished 6-TG incorporation into nucleic acids. Similarly, guanine antagonized 6-TG cytotoxicity in a dose dependent fashion. Furthermore, guanine (200 μM) fully suppressed the 6-TG (10 μM) induced HL-60 cell differentiation, which suggests that cell differentiation at pharmacological 6-TG concentrations is dependent on the anabolism of the drug to active nucleotides. 6-TG given alone reduced GTP levels and DNA synthesis rates in HL-60 cells, while a major intracellular 6-TG metabolite, 6-thioguanosine 5'-monophosphate, accumulated to high levels (~100 μM). It is suggested that accumulation of 6-thioguanosine 5'-monophosphate and a resultant partial block of the de novo biosynthesis of guanine nucleotides is responsible for 6-TG induced cell differentiation in HL-60 cells.

Original languageEnglish
Pages (from-to)3648-3651
Number of pages4
JournalCancer Research
Volume48
Issue number13
Publication statusPublished - 1988
Externally publishedYes

Fingerprint

Thioguanine
HL-60 Cells
Leukemia
Guanine
Cell Differentiation
Nucleotides
Guanine Nucleotides
guanine-6-thioguanine
Guanosine Triphosphate
Nucleic Acids
Organism Cloning
Pharmacology
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Modulation of 6-thioguanine activity by guanine in human promyelocytic leukemia HL-60 cells. / Cheng, H. W.; Armstrong, R. D.; Sadee, W.

In: Cancer Research, Vol. 48, No. 13, 1988, p. 3648-3651.

Research output: Contribution to journalArticle

Cheng, H. W. ; Armstrong, R. D. ; Sadee, W. / Modulation of 6-thioguanine activity by guanine in human promyelocytic leukemia HL-60 cells. In: Cancer Research. 1988 ; Vol. 48, No. 13. pp. 3648-3651.
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