Deoxycytidine preferentially protects normal versus leukemic myeloid progenitor cells from cytosine arabinoside-mediated cytotoxicity

K. Bhalla, W. MacLaughlin, J. Cole, Z. Arlin, M. Baker, G. Graham, S. Grant

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

We examined the ability of high concentrations of the naturally occurring nucleoside deoxycytidine (dCyd) to reverse the cytotoxicity of high (eg, ≥10-5 mol/L) concentrations of 1-B-D arabinofuranosylcytosine (Ara-C) toward normal (CFU-GM) and leukemic myeloid progenitor cells (L-CFU). Leukemic myeloblasts from patients with acute nonlymphocytic leukemia (ANLL) and normal human bone marrow mononuclear cells were cultured in soft agar in the continuous presence of 10-5 to 5 x 10-5 mol/L of Ara-C together with dCyd (10-4 to 5 x 10-3 mol/L). Administration of 10-5 mol/L of Ara-C alone eradicated colony formation in all samples tested. Coadministration of 10-3 mol/L of dCyd restored 72.2% of control colony formation for CFU-GM, but only 10.9% for L-CFU. When higher concentrations of Ara-C (eg, 5 x 10-5 mol/L) were administered, dCyd-mediated protection toward CFU-GM decreased, but remained significantly greater than that observed for L-CFU. Incubation with 10-3 mol/L of dCyd reduced the 4-hour intracellular accumulation of the triphosphate derivative of Ara-C (Ara-CTP) in both normal and leukemic cells by >98%; under identical conditions, a significant expansion of the intracellular of the triphosphate derivative of dCyd (dCTP) pools was observed in the normal bone marrow mononuclear cells but not in leukemic blasts. This finding was associated with a greater reduction in Ara-C DNA incorporation in normal elements. These in vitro studies suggest that dCyd may preferentially protect normal v leukemic myeloid progenitor cells from the lethal actions of high-dose Ara-C.

Original languageEnglish (US)
Pages (from-to)568-571
Number of pages4
JournalBlood
Volume70
Issue number2
DOIs
StatePublished - 1987
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Deoxycytidine preferentially protects normal versus leukemic myeloid progenitor cells from cytosine arabinoside-mediated cytotoxicity'. Together they form a unique fingerprint.

Cite this