Glucocorticosteroids induce DNA fragmentation in human lymphoid leukemia
cells
CW Distelhorst
Department of Medicine, Case Western Reserve University School of Medicine,
Cleveland, OH 44106.
The present study was undertaken to investigate the potential role of
glucocorticoid-induced DNA damage in the lysis of human lymphoid leukemia
cells by glucocorticoids. Lymphoblasts were isolated from patients with
acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia (CML) in
blast crisis and cultured in vitro with or without dexamethasone. DNA was
then purified from the cells and analyzed by agarose gel electrophoresis.
Only high molecular weight (mol wt) DNA was present in cells cultured
without dexamethasone, but a ladder of DNA fragments ranging in size from
180 to 200 base pairs (bp) to greater than 1,500 bp was present in cells
cultured with dexamethasone. The DNA fragments were multiples of 180 to 200
bp, suggesting an internucleosomal site of DNA cleavage. The same pattern
of DNA fragmentation was detected in normal thymocytes isolated from
adrenalectomized rats following in vivo treatment with dexamethasone and in
S49 mouse thymoma cells after in vitro incubation with dexamethasone.
Dexamethasone-induced DNA fragmentation preceded overt loss of viability in
glucocorticoid-sensitive cells but was not detected in two variants of the
S49 cell line that are glucocorticoid resistant owing to glucocorticoid
receptor defects. The results suggest that glucocorticoids kill human
lymphoblastic leukemia cells and both normal and malignant murine
thymocytes by a common mechanism that involves glucocorticoid induction of
an endonucleolytic activity with cleavage of genomic DNA.
Volume 72,
Issue 4,
pp. 1305-1309,
10/01/1988
Copyright © 1988 by The American Society of Hematology
