Benzene metabolite

Schnellman, R.G. and Mandel, L.J. (1986). Cellular toxicity of bromobenzene and bromo-benzene metabolites to rabbit proximal tubules The role and mechanism of 2-bromohy-droquinone. J. Pharmacol. Exp. Then 237 456 161. 

Chen H, Eastmond DA. 1995a. Synergistic increase in chromosomal breakage within the euchromatin induced by an interaction of the benzene metabolites phenol and hydroquinone in mice. Carcinogenesis 16 1963-1969. 

Legathe A, Hoener B-A, Tozer TN. 1994. Pharmacokinetic interaction between benzene metabolites, phenol and hydroquinone, in B6C3F1 mice. Toxicol Appl Pharmacol 124 131-138. 

Morimoto K, Wolff S. 1980. Increase of sister chromatid exchanges and perturbations of cell division kinetics in human lymphocytes by benzene metabolites. Cancer Res 40 118-1193. 

Morimoto K, Wolff S, Koizumi A. 1983. Induction of sister-chromatid exchanges in human lymphocytes by microsomal activation of benzene metabolites. Mutat Res 119 355-360. 

Pellack-Walker P, Blumer JL. 1986. DNA damage in L5178YS cells following exposure to benzene metabolites. Mol Pharmacol 39 42-47. 

Seaton MJ, Schlosser PM, Medinsky MA. 1995. In vitro conjugation of benzene metabolites by human liver Potential influence of interindividual variability on benzene toxicity. Carcinogenesis 16 1519-1527. 

A large number of studies have investigated the metabolism of benzene per se or in relation to toxification and, particularly, myelotoxicity. Most evidence shows that benzene oxide (10.1, Fig. 10.8) is not the ultimate toxic species, as was initially believed. Indeed, phenol and quinone metabolites of benzene are more active in forming adducts with macromolecular nucleophiles and eliciting cellular toxicity. For example, the efficacy of benzene metabolites (see Fig. 10.8) to inhibit DNA synthesis in a mouse lymphoma cell line decreased in the order benzoquinone (10.17) > hydroquinone (10.16)... 

P. Pellack-Walker, J. K. Walker, H. H. Evans, J. L. Blumer, Relationship between the Oxidation Potential of Benzene Metabolites and Their Inhibitory Effect on DNA Synthesis in L5178YS Cells , Mol. Pharmacol. 1985, 28, 560 - 566. 

The mechanism of benzene-induced toxicity appears to involve the concerted action of several benzene metabolites. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and opened-ring products that are transported to the bone marrow, where secondary metabolism occurs. Metabolites may induce toxicity both by covalent binding to cellular macromolecules and by inducing oxidative damage. Metabolites may also inhibit stromal cells, which are necessary to support growth of differentiating and maturing marrow cells. ... 

Waidyanatha S., Rothman N., Li G., Smith M. T., Yin S. Rappaport S. M. Rapid determination of six urinary benzene metabolites in occupationally exposed and unexposed subjects. Analytical Biochemistry 2004 327(2) 184-199. 

Catechol may be oxidized by peroxidases to the reactive intennediate benzo-1,2-quinone, which readily binds to proteins (Bhat et al., 1988) this process, catalysed by rat or human bone-marrow cells in the presence of H2O2 (0.1 mM), is stimulated by phenol (0.1-10 mM), and decreased by hydroquinone and by glutathione, which conjugates with benzo-l,2-quinone. These phenols (phenol, catechol and hydroquinone) may play a role in benzene toxicity to bone marrow all three are formed as benzene metabolites (Smith et al., 1989) and they interact in several ways as far as their bioactivation by (myelo)peroxidases is concerned (Smith et al., 1989 Subrahmanyam et al., 1990). 

Chapman. D.E.. Namkung, M.J. Juchau, M.R. (1994) Benzene and benzene metabolites as embryotoxic agents effects on cultured rat embryos. Toxicol, appl. Pharmacol., 128, 129— 137... 

Frantz, C.E., Chen, H. Eastmond, D.A. (1996) Inhibition of hiunan topoisomerase II in vitro by bioactive benzene metabolites. Environ. Health Perspect.. 104 (Suppl. 6), 1319-1323... 

Irons, R.D., Stillman, W.S., Colagiovanni, D.B. Henry, V.A. (1992) Synergistic action of the benzene metabolite hydroquinone on myelopoietic stimulating activity of granulocyte/macro-phage colony-stimulating factor in vitro. Proc. natlAcad. Sci. USA, 89, 3691-3695... 

Levay, G. Bodell. W.J. (1996) Role of hydrogen peroxide in the formation of DNA adducts in HL-60 cells treated with benzene metabolites. Biochem. biophys. Res. Comm., 222, 44-49... 

Maiming, B.W, Adams, D.O. Lewis, J.G. (1994) Effects of benzene metabolites on receptor-... 

Moran, J.L., Siegel, D., Sun, X.-M. Ross, D. (1996) Induction of apoptosis by benzene metabolites in HL60 and CD34 human bone marrow progenitor cells. Mol. Pharmacol., 50, 610-615... 

Robertson, M.L., Eastmond, D.A. Smith, M.T. (1991) Two benzene metabolites, catechol and hydroquinone, produce a synergistic induction of micronuclei and toxicity in cultured human lymphocytes. Mutat. Res., 249, 201-209... 

Seidel, H.J., Barthel, E., Schafer, E, Schad, H. Weber, L. (1991) Action of benzene metabolites on murine hematopoietic colony-forming cells in vitro. Toxicol, appl. Pharmacol., Ill, 128-131... 

Carbonnelle, R, Lison, D., Leroy, J.-Y. Lauwerys, R. (1995) Effect of the benzene metabolite, hydroquinone, on interleukin-1 secretion by human monocytes in vitro. Toxicol, appl. Pharmacol., 132, 220-226... 

Eastmond, D.A., Rupa. D.S. Hasegawa, L.S. (1994) Detection of hyperdiploidy and chromosome breakage in interphase human lymphocytes following exposure to the benzene metabolite hydroquinone using multicolor fluorescence in situ hybridization with DNA probes. Mutat. Res., 322, 9-20... 

Marrazzini, A., Chelotti, L., Barrai, I., Loprieno, N. Barale, R. (1994a) In vivo genotoxic interactions among three phenolic benzene metabolites. Mutat. Res., 341, 29-46... 

Tunek, A., Hflgstedt. B. Olofsson, T. (1982) Mechanism of benzene toxicity. Effects of benzene and benzene metabolites on bone marrow cellularity, number of granulopoietic stem cells and frequency of micronuclei in mice. Chem.-biol. Interact., 39, 129-138... 

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