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

نویسندگان

  • B A Hazel
  • A O'Connor
  • R Niculescu
  • G F Kalf
چکیده

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) myeloblasts. Both compounds interact with cellular signaling pathways normally activated by granulocyte colony stimulating factor (G-CSF) and can replace the requirement for G-CSF. While IL-3 induces a growth response in 32D.3 (G) cells, G-CSF has been shown to provide both growth and differentiated signals. Both HQ and LTD4 induce differentiation and synergize with IL-3 for growth; however, neither supports growth in the absence of IL-3. Benzene, like HQ, also provides a differentiation signal for 32D cells; however, it has no effect on their growth. Unlike G-CSF, benzene, or LTD4, each of which stimulates terminal differentiation; HQ blocks differentiation at the myelocyte stage, allowing only a small percentage of progenitors to proceed to mature segmented granulocytes. Benzene- and G-CSF-induced differentiation were prevented by the additional of either LPO inhibitors or LTD4 receptor antagonists, indicating that benzene, like G-CSF, upregulates LTD4 production. Hydroquinone-induced differentiation was not affected by the LPO inhibitors, but only by the specific receptor antagonists. Thus HQ appears to obviate the requirement for LTD4 by activating the LTD4 receptor directly.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Enhancement of myeloid cell growth by benzene metabolites via the production of active oxygen species.

In low concentrations, benzene and its metabolite hydroquinone are known to have diverse biological effects on cells, including the synergistic stimulation with GM-CSF of hematopoietic colony formation in vitro, stimulation of granulocytic differentiation in vitro and in vivo, and general suppression of hematopoiesis in vivo. These chemicals are also known to be active in the induction of activ...

متن کامل

Isolation, Induction of Neural and Glial Differentiation and Evaluating the Expression of Five Self Renewal Genes in Adult Mouse Neural Stem Cells

Purpose: Isolation, induction of neural and glial differentiation and evaluating the expression of Nucleostemin, ZFX, Hoxb-4, Sox-9 & Bmi-1 self renewal genes in adult mouse neural stem cells. Materials and Methods: Breifly, for isolation of neural stem cells, frontal part of adult mouse brain was minced in PBS and digested by enzyme solution, containing hyaloronidase and trypsin. Isolated cel...

متن کامل

I-11: Dedifferentiation of Mouse Fibroblast Cells by Chemical Induction

Induced pluripotent stem cells (iPSCs) generated by ectopic expression of four transcription factors have great promises for regenerative medicine in humans. Since the initial report of iPSCs by viral transfection, ample efforts have been made in the generation of iPSCs through nonviral approaches. Small molecules offer the advantages of low cost without genomic modification and have been used ...

متن کامل

Study on Effect of Head, Tail, and Limbud extracts of Mouse on Differentiation of Hair Follicle Stem Cells to Neural cells

Introduction: Adult stem cells are the group of cells which conserve their nature in tissues and organs among other cells. In recent years, the researchers reported the existence of stem cells on the Bulge of hair follicles near to the smooth muscle. It is possible to differentiate these stem cells to neural cells by induction of Shh, FGF, and RA factors. Because of existence of these factors ...

متن کامل

Induced differentiation of HL-60 promyelocytic leukemia cells to monocyte/macrophages is inhibited by hydroquinone, a hematotoxic metabolite of benzene.

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 induce...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Environmental Health Perspectives

دوره 104  شماره 

صفحات  -

تاریخ انتشار 1996