The effect of rh-cytokines on the sensitivity of normal human CFU-GM progenitors to Ara-C and on the S-phase activity of light density human bone marrow cells.
This study examines the effect of pre-incubation in liquid phase of normal human CFU-GM progenitors with recombinant human (rh) cytokines prior to exposure to cytosine arabinoside (Ara-C) in clonogenic culture. Light density marrow cells (LMDCs) were preincubated in Biorich (chemically defined serum-free complete medium) with G + GM-CSF or IL-3 prior to semi-solid culture with Ara-C (10(-4) M-10(-12) M). Cell cycle analysis was performed by flow cytometry pre- and post-rh-cytokine treatment. Data from 26 normal marrows studied clonogenically, demonstrated a 60% reduction in CFU-GM with 10(-4) M Ara-C. Preincubation in Biorich medium with the addition of G + GM-CSF or IL-3 caused a significant enhancement of sensitivity to Ara-C across the dose curve. Biorich medium alone had an apparent protective effect resulting in amelioration of the cytotoxic effect of Ara-C. Cell cycle analysis of eight subjects showed significant recruitment into S-phase following pre-treatment with cytokines. A reduction in S-phase activity was noted in cells pre-incubated in Biorich alone. In summary, it would appear that cytokines can enhance the sensitivity of normal CFU-GM to Ara-C in vitro possibly due to an increase in S-phase activity. Pre-incubation in nutrient medium without cytokines resulted in cell quiescence.
Smith
M A
MA
Department of Haematology, Royal United Hospital, N.H.S. Trust, Combe Park, Bath, U.K.
Smith
J G
JG
Provan
A B
AB
Singer
C R
CR
D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002452:Cell Count; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D016196:S Phase
D016207:Cytokines; D007377:Interleukin-3; D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor