Induced differentiation of HL-60 promyelocytic leukemia cells to
monocyte/macrophages is inhibited by hydroquinone, a hematotoxic metabolite
of benzene
NL Oliveira and GF Kalf
Department of Biochemistry and Molecular Biology, Jefferson Medical
College, Thomas Jefferson University, Philadelphia, PA 19107.
Chronic exposure of humans to benzene has been shown to have a cytotoxic
effect on hematopoietic progenitor cells in intermediate stages of
differentiation, which can lead to aplastic anemia and acute myelogenous
leukemia. We studied the effect of hydroquinone (HQ), a toxic metabolite of
benzene found in the bone marrow, on the human promyelocytic leukemia cell
line (HL-60), which can be induced to differentiate to both monocyte and
myeloid cells, and thus has been used as a surrogate for a
granulocyte/macrophage progenitor cell. Exposure of HL-60 cells to
noncytotoxic concentrations of HQ for 3 hours before induction with phorbol
myristate acetate (TPA) caused a dose-dependent inhibition of the
acquisition of characteristics of monocytic differentiation, such as
adherence, nonspecific esterase (NSE) activity, and phagocytosis, but had
no effect on cell proliferation. HQ appeared to be affecting maturation
beyond the monoblast/promonocyte stages. HQ also prevented differentiation
induced by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]; however, the block
occurred after the acquisition of adherence. HQ at concentrations that
inhibited monocytic differentiation had no effect on differentiation to
granulocytes, suggesting that the block in the differentiation of these
bipotential cells is a step unique to the monocytic pathway. HQ was unable
to prevent differentiation induced by the macrophage-derived cytokine,
interleukin (IL)-1, a differentiation factor for cells of the monocytic
lineage.
Volume 79,
Issue 3,
pp. 627-633,
02/01/1992
Copyright © 1992 by The American Society of Hematology
