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 agents appear to react with nucleophilic sulfhydryl groups essential for guanosine triphosphate binding to tubulin that are particularly sensitive to sulfhydryl-alkylating agents.
- Research Organization:
- Chemical Industry Institute of Toxicology, Research Triangle Park, NC
- OSTI ID:
- 5583209
- Journal Information:
- J. Toxicol. Environ. Health; (United States), Vol. 16:5
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
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)