Induction of granulocytic differentiation in a mouse model by benzene and hydroquinone.

Chronic exposure of humans to benzene causes acute myelogenous leukemia (AML). The studies presented here were undertaken to determine whether benzene, or its reactive metabolite, hydroquinone (HQ), affects differentiation of myeloblasts. Benzene or HQ administered to C57BL/6J mice specifically induced granulocytic differentiation of myeloblasts. The ability of these compounds to induce differentiation of the myeloblasts was tested directly using the murine interleukin 3 (IL-3)-dependent 32D.3 (G) myeloblastic cell line, and the human HL-60 promyelocytic leukemia cell line. We have previously shown that benzene treatment of HL-60 myeloblasts activates protein kinase C (PKC) and upregulates the 5-lipoxygenase (LPO) pathway for the production of leukotriene D4 (LTD4), an essential effector or granulocytic differentiation. Differentiation was prevented by sphinganine, a PKC inhibitor, and, as shown here, by LPO inhibitors and LTD4 receptor antagonists. Benzene or HQ also induces differentiation in 32D.3 (G) ...