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1,25-dihydroxycholecalciferol-induced differentiation of myelomonocytic leukemic cells unresponsive to colony stimulating factors and phorbol esters

Journal Article · · J. Cell. Physiol.; (United States)
; ; ;
The murine myelomonocytic leukemia cell line WEHI-3B D/sup +/, which differentiates in response to granulocyte colony stimulating factor (G-CSF), can also be induced to differentiate into monocyte-macrophages by phorbol myristate acetate (PMA) treatment, whereas the WEHI-3B D/sup -/ subline, which is unresponsive to G-CSF and PMA, can be induced to differentiate to granulocytes as well as monocytes by 1,25-dihydroxycholecalciferol (1,25-(OH)/sub 2/ D3), the biologically active metabolite of vitamin D3. A newly developed variant of the WEHI-3B D/sup +/ line, named WEHI-3B D/sup +/G, which was responsive to G-CSF but not to PMA, was also differentiated to granulocytes by 1,25-(OH)/sub 2/ D3. Although vitamin D3 has been reported to induce macrophage differentiation in responsive tumor cells, this is the first demonstration that 1,25-(OH)/sub 2/ D3 can induce granulocyte differentiation. In both differentiation pathways, cessation of cellular proliferation accompanies changes in morphologic and cytochemical properties of the cells. This suggests that leukemic cell lines unresponsive to differentiation agents acting at the cell surface retain their ability to differentiate in response to agents that do not act via the plasma membrane such as 1,25-(OH)/sub 2/ D3, which has cytosolic/nuclear receptors. These results suggest that low doses of 1,25-(OH)/sub 2/ D3 may be useful in combination with hemopoietic growth factors (CSFs) as therapeutic agent to induce leukemic cell differentiation in vivo.
Research Organization:
NIH, Frederick, MD
OSTI ID:
6785471
Journal Information:
J. Cell. Physiol.; (United States), Journal Name: J. Cell. Physiol.; (United States) Vol. 129:3; ISSN JCLLA
Country of Publication:
United States
Language:
English

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Related Subjects

550301 -- Cytology-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
CARCINOGENS
CELL CONSTITUENTS
CELL DIFFERENTIATION
CELL MEMBRANES
CHOLECALCIFEROL
COLONY FORMATION
DISEASES
ESTERS
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
LEUKEMIA
MEMBRANE PROTEINS
MEMBRANES
NEOPLASMS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHORBOL ESTERS
PROTEINS
PYRIMIDINES
RECEPTORS
RIBOSIDES
THYMIDINE
TRITIUM COMPOUNDS
TUMOR CELLS
VITAMIN D
VITAMINS