Induction of apoptosis by benzene metabolites in HL60 and CD34+ human bone marrow progenitor cells

JL Moran, D Siegel, XM Sun and D Ross

Molecular Toxicology and Environmental Health Sciences Program, School of Pharmacy and Cancer Center, University of Colorado Health Sciences Center, Denver 80262, USA.

Two cell types, HL60 human promyelocytic leukemia cells and CD34+ human bone marrow progenitor cells, were used as model systems to explore a possible role for apoptosis in the myelotoxicity of the phenolic metabolites of benzene. HL60 cells were treated with either phenol, catechol, hydroquinone, or 1,2,4-benzenetriol and then stained with Hoechst 33342 and propidium iodide and subjected to fluorescent microscopy. Cells with nuclear condensation and fragmentation were scored as apoptotic, and etoposide (40 microM) was used as a positive control. Catechol, 1,2,4-benzenetriol, and hydroquinone induced marked time- (0-24 hr) and concentration- (25-100 microM) dependent apoptosis, whereas phenol (750 microM) did not. Under these conditions, no significant necrosis was observed. The induction of apoptosis was confirmed by internucleosomal cleavage of DNA, assessed by agarose gel electrophoresis. CD34+ cells treated with etoposide (40 microM) or hydroquinone (50 microM) for 18 hr were stained and subjected to fluorescent microscopy as above. The percentage of cells exhibiting nuclear condensation and/or fragmentation as well as high intensity staining significantly increased in both cases. The induction of apoptosis was confirmed using a terminal deoxynucleotidyl transferase assay. These data show that apoptosis can be induced in both HL60 and CD34+ human bone marrow progenitor cells by benzene metabolites. The ability of phenolic metabolites of benzene to induce apoptosis in human bone marrow progenitor cells may contribute to benzene myelotoxicity.

Volume 50, Issue 3, pp. 610-615, 09/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				L. H. Stockwin, M. A. Bumke, S. X. Yu, S. P. Webb, J. R. Collins, M. G. Hollingshead, and D. L. Newton Proteomic Analysis Identifies Oxidative Stress Induction by Adaphostin Clin. Cancer Res., June 15, 2007; 13(12): 3667 - 3681. [Abstract] [Full Text] [PDF]

				X. Zheng, R. L. Chang, X.-X. Cui, G. E. Avila, V. Hebbar, M. Garzotto, W. J. Shih, Y. Lin, S.-E. Lu, A. B. Rabson, et al. Effects of 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Combination with Paclitaxel (Taxol) on Prostate Cancer LNCaP Cells Cultured In vitro or Grown as Xenograft Tumors in Immunodeficient Mice. Clin. Cancer Res., June 1, 2006; 12(11): 3444 - 3451. [Abstract] [Full Text] [PDF]

				D. J. Abernethy, E. V. Kleymenova, J. Rose, L. Recio, and B. Faiola Human CD34+ Hematopoietic Progenitor Cells Are Sensitive Targets for Toxicity Induced by 1,4-Benzoquinone Toxicol. Sci., May 1, 2004; 79(1): 82 - 89. [Abstract] [Full Text] [PDF]

				B. Faiola, A. K. Bauer, E. S. Fuller, V. A. Wong, L. J. Pluta, D. J. Abernethy, J. B. Mangum, J. I. Everitt, and L. Recio Variations in Prkdc and Susceptibility to Benzene-Induced Toxicity in Mice Toxicol. Sci., October 1, 2003; 75(2): 321 - 332. [Abstract] [Full Text] [PDF]

				T. Yamauchi, M. J. Keating, and W. Plunkett UCN-01 (7-Hydroxystaurosporine) Inhibits DNA Repair and Increases Cytotoxicity in Normal Lymphocytes and Chronic Lymphocytic Leukemia Lymphocytes Mol. Cancer Ther., February 1, 2002; 1(4): 287 - 294. [Abstract] [Full Text] [PDF]

				J. L. Moran, D. Siegel, and D. Ross A potential mechanism underlying the increased susceptibility of individuals with a polymorphism in NAD(P)H:quinone oxidoreductase 1 (NQO1) to benzene toxicity PNAS, July 6, 1999; 96(14): 8150 - 8155. [Abstract] [Full Text] [PDF]

				M.-L. Kuo, S.-G. Shiah, C.-J. Wang, and S.-E. Chuang Suppression of Apoptosis by Bcl-2 to Enhance Benzene Metabolites-Induced Oxidative DNA Damage and Mutagenesis: A Possible Mechanism of Carcinogenesis Mol. Pharmacol., May 1, 1999; 55(5): 894 - 901. [Abstract] [Full Text]