Hydrocortisone in culture protects the blast cells in acute myeloblastic leukemia from the lethal effects of cytosine arabinoside

Journal Article · Mon Jul 01 00:00:00 EDT 1991 · Journal of Cellular Physiology; (United States)

DOI:https://doi.org/10.1002/jcp.1041480108· OSTI ID:5263360

Yang, G S; Wang, C; Minkin, S; Minden, M D; McCulloch, E A ^[1]

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1. Ontario Cancer Institute, University of Toronto (Canada)

The blast cells in acute myeloblastic leukemia (AML) respond to many of the same regulatory mechanisms that control normal hemopoiesis. These include the growth factors that bind to membrane receptors and steroid hormones or vitamins that have intracellular receptors. The authors report the effects in culture of the steroid glucocorticoid hydrocortisone on freshly explanted AML blasts from patients and on two continuous AML cell lines. Only small changes in clonogenic cell numbers in suspension cultures were seen in the presence of hydrocortisone. The most striking effect of the hormone was on the sensitivity of blasts cells to cytosine arabinoside (ara-C). In contrast to the response of AML blast cells to retinoic acid, a ligand for intracellular steroid receptors that sensitizes some blast populations to ara-C, hydrocortisone reduced the toxic effects of the drug. The protective action of hydrocortisone was not mediated through the cell cycle since exposure of blasts to hydrocortisone did not affect the percentage of cells in DNA synthesis as measured with the tritiated thymidine (3HTdR) suicide technique. The hydrocortisone effect could be demonstrated using a pulse (20 min) exposure protocol. Blasts pulsed with increasing specific activities of 3HTdR showed the usual response pattern with an initial loss in plating efficiency to about 50% of control, followed by a plateau, regardless of whether the cells had been exposed to hydrocortisone. Control blasts exposed to increasing ara-C concentrations gave very similar dose-response curves; in striking contrast, blast cells cultured in hydrocortisone, then pulsed with ara-C did not lose colony-forming ability even though the same population was sensitive to 3HTdR.

• OSTI ID: 5263360
• Journal Information: Journal of Cellular Physiology; (United States), Vol. 148:1; ISSN 0021-9541
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTINEOPLASTIC DRUGS
TOXICITY
HYDROCORTISONE
BIOLOGICAL FUNCTIONS
MYELOID LEUKEMIA
PATHOGENESIS
TUMOR CELLS
SENSITIVITY
CELL CULTURES
DNA
DOSE-RESPONSE RELATIONSHIPS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ANIMAL CELLS
AZINES
CORTICOSTEROIDS
DISEASES
DRUGS
GLUCOCORTICOIDS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
IMMUNE SYSTEM DISEASES
ISOTOPE APPLICATIONS
KETONES
LEUKEMIA
NEOPLASMS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PREGNANES
PYRIMIDINES
RIBOSIDES
STEROID HORMONES
STEROIDS
550901* - Pathology- Tracer Techniques
550201 - Biochemistry- Tracer Techniques