S1-phase cells of the leukemic cell cycle sensitive to 1-beta-D-arabinofuranosylcytosine at a high-dose level

Journal Article · Mon Jul 01 04:00:00 EDT 1985 · Cancer Res.; (United States)

OSTI ID:5179369

Smets, L A; Homan-Blok, J

To investigate the effects of 1-beta-D-arabinofuranosylcytosine (ara-C) at high doses as applied in human acute leukemia, the cytotoxic effect of high-dose ara-C was studied in L1210 leukemia cells grown in tissue culture or as tumors in syngeneic mice. Exponentially growing cells displayed the expected S-phase specificity and dose saturation properties of drug action. In contrast, in stationary cultures, progressively more cells were killed by increasing the concentration of the drug. Moreover, the fraction of cells killed at high doses exceeded by 2- to 3-fold the number of cells in drug-sensitive S phase detectable by flow cytometry or (/sup 3/H)thymidine radioautography. To identify these apparent non-S targets of ara-C at high doses, L1210 cells were separated according to cell cycle position by velocity sedimentation at unit gravity. Large fractions of cells, accumulating at the G1-S boundary by nutrient starvation, were detected in stationary tissue culture cells as well as in ascites or solid tumor cells. The cells located in this cell cycle compartment (termed S1 cells) were sensitive to the cytotoxic effect of high-dose ara-C. The putative presence of similar S1 fractions in advanced human acute nonlymphocytic leukemia may explain in part the clinical efficacy of a high-dose application of the drug.

• Research Organization: Netherlands Cancer Institute, Amsterdam
• OSTI ID: 5179369
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 7; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
550600* -- Medicine
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
AZINES
BIOLOGICAL EFFECTS
CELL CYCLE
CHEMOTHERAPY
CYTOSINE
DISEASES
DOSE-RESPONSE RELATIONSHIPS
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKEMIA
MAMMALS
MICE
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PYRIMIDINES
RODENTS
SENSITIVITY
THERAPY
TISSUE CULTURES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
VERTEBRATES