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Title: Quinones as toxic metabolites of benzene

Occupational exposure to benzene has long been associated with toxicity to the blood and bone marrow, including lymphocytopenia, pancytopenia, aplastic anemia, acute myelogenous leukemia, and possible lymphoma. A variety of studies have established that benzene itself is not the toxic species but requires metabolism to reactive intermediates. The bioactivation of benzene is complex. Both primary and secondary oxidation of benzene and its metabolites are mediated via cytochrome P-450 in the liver, although the role of secondary metabolism in the bone marrow is not clear. Toxicity is associated with the dihydroxy metabolites, hydroquinone and catechol, which concentrate in bone marrow. Hydroquinone and its terminal oxidation product, p-benzoquinone, have been demonstrated to be potent suppressors of cell growth in culture. Suppression of lymphocyte blastogenesis by these compounds is a sulfhydryl-dependent process and occurs at concentrations that do not result in cell death, or in detectable alterations in energy metabolism, intracellular glutathione concentration, or protein synthesis. Recent studies suggest that these compounds and other membrane-penetrating sulfyhdryl alkylating agents, such as N-ethylmaleimide and cytochalasin A, and endogenous regulatory molecules, such as soluble immune response suppressor (SIRS), interfere with microtubule assembly in vitro and selectively interfere with microtubule-dependent cell functions at identical concentrations. These agentsmore » appear to react with nucleophilic sulfhydryl groups essential for guanosine triphosphate binding to tubulin that are particularly sensitive to sulfhydryl-alkylating agents.« less
Authors:
Publication Date:
OSTI Identifier:
5583209
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Toxicol. Environ. Health; (United States); Journal Volume: 16:5
Research Org:
Chemical Industry Institute of Toxicology, Research Triangle Park, NC
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; BENZENE; METABOLIC ACTIVATION; OCCUPATIONAL EXPOSURE; LYMPHOCYTES; INHIBITION; QUINONES; TOXICITY; BONE MARROW; CELL CULTURES; CYTOCHROMES; METABOLITES; ANIMAL CELLS; ANIMAL TISSUES; AROMATICS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY; BODY FLUIDS; CONNECTIVE TISSUE CELLS; HEMATOPOIETIC SYSTEM; HYDROCARBONS; LEUKOCYTES; MATERIALS; ORGANIC COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; ORGANS; PIGMENTS; PROTEINS; SOMATIC CELLS; TISSUES 560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)