Benzene and its metabolite, hydroquinone, induce granulocytic differentiation in myeloblasts by interacting with cellular signaling pathways activated by granulocyte colony-stimulating factor

Stem Cells
B A HazelG F Kalf

Abstract

Chronic exposure of humans to benzene (BZ) causes acute myelogenous leukemia. These studies determined whether BZ, or its reactive metabolite, hydroquinone (HQ), affect differentiation of myeloblasts. BZ or HQ administered to C57BL/6J mice specifically induced terminal granulocytic differentiation of myeloblasts. The ability of the compounds to induce differentiation of the myeloblast was tested directly using the murine interleukin 3 (IL-3)-dependent myeloblastic cell line, 32D.3 (G) and the human HL-60 promyelocytic leukemic cell line. Treatment of HL-60 myeloblasts with BZ activated protein kinase C and upregulated the 5-lipoxygenase (LPO) pathway for the production of leukotriene D4 (LTD4), an essential effector of granulocytic differentiation. Differentiation was prevented by sphinganine, a kinase C inhibitor, as well as by LPO inhibitors and LTD4 receptor antagonists. BZ and HQ also induced differentiation in 32D.3 (G) myeloblasts. Both compounds interact with cellular signaling pathways activated by granulocyte colony-stimulating factor (G-CSF) and thus replace the requirement for G-CSF. IL-3 induces a growth response, whereas G-CSF provides both growth and differentiation signals. BZ does not induce growth in the absenc...Continue Reading

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Citations

Sep 1, 1997·Journal of Toxicology and Environmental Health·V HaufroidR Lauwerys
May 23, 1998·Annual Review of Pharmacology and Toxicology·T J Monks, S S Lau
Dec 1, 1996·Environmental Health Perspectives·B A HazelG F Kalf
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Jun 15, 2011·Toxicology·André Luiz Teroso RibeiroSandra Helena Poliselli Farsky
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Nov 6, 2013·Biological & Pharmaceutical Bulletin·Yu InoueHirohiko Akamatsu
Feb 24, 1998·Annals of the New York Academy of Sciences·U Rangan, R Snyder

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