The Effects of Benzene and Hydroquinone on Myeloid Differentiation of HL-60 Promyelocytic Leukemia Cells

Chronic exposure of humans to benzene (BZ) affects hematopoietic progenitor cells in intermediate stages of differentiation which can lead to aplastic anemia and/or acute myelogenous leukemia and some of its variant forms. We studied the effects of BZ and hydroquinone (HQ), a toxic bone marrow metabolite, on the human HL-60 promyelocytic leukemic cell line. Because the HL-60 cell is bipotential and can be induced to differentiate to monocytes or granulocytes it has been used in many studies as a surrogate for the granulocyte/macrophage committed cell, GM-CFU. Treatment of HL-60 cells with BZ specifically induced differentiation along the granulocytic lineage as measured by morphology, induction of superoxide production and chloroacetate esterase activity and the appearance of the L12-2 surface antigen. Differentiation was induced via the activation of protein kinase C and the phosphorylation of several proteins known to be involved in HL-60 cell differentiation. Subsequent to kinase C activation, arachidonic acid was released from membrane phospholipids and the 5-lipoxygenase pathway was activated for the production of leukotriene D4 (LTD4) required for granulocytic differentiation. BZ induction of granulopoiesis was prevented by preincubation of HL-60 cells with inhibitors of protein kinase C, 5-lipoxygenase, gamma-glutamyl transpeptidase required for the conversion of LTC4 to LTD4, or LTD4 receptor antagonists. Treatment of HL-60 cells with tetraphorbol myristate acetate (TPA), 1 alpha, 25-dihydroxyvitamin D3 (1,25-(OH2)D3) or interleukin-1 (IL-1) induced HL-60 cells to differentiate to monocytes/macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)