Metabolism of phenol and hydroquinone to reactive products by macrophage peroxidase or purified prostaglandin H synthase
- Thomas Jefferson Univ., Philadelphia, PA (USA)
Macrophages, an important cell-type of the bone marrow stroma, are possible targets of benzene toxicity because they contain relatively large amounts of prostaglandin H synthase (PHS), which is capable of metabolizing phenolic compounds to reactive species. PHS also catalyzes the production of prostaglandins, negative regulators of myelopoiesis. Studies indicate that the phenolic metabolites of benzene are oxidized in bone marrow to reactive products via peroxidases. With respect to macrophages, PHS peroxidase is implicated, as in vivo benzene-induced myelotoxicity is prevented by low doses of nonsteroidal anti-inflammatory agents, drugs that inhibit PHS. Incubations of either 14C-phenol or 14C-hydroquinone with a lysate of macrophages collected from mouse peritoneum (greater than 95% macrophages), resulted in an irreversible binding to protein that was dependent upon H2O2, incubation time, and concentration of radiolabel. Production of protein-bound metabolites from phenol or hydroquinone was inhibited by the peroxidase inhibitor aminotriazole. Protein binding from 14C-phenol also was inhibited by 8 microM hydroquinone, whereas binding from 14C-hydroquinone was stimulated by 5 mM phenol. The nucleophile cysteine inhibited protein binding of both phenol and hydroquinone and increased the formation of radiolabeled water-soluble metabolites. Similar to the macrophage lysate, purified PHS also catalyzed the conversion of phenol to metabolites that bound to protein and DNA; this activation was both H2O2- and arachidonic acid-dependent. These results indicate a role for macrophage peroxidase, possibly PHS peroxidase, in the conversion of phenol and hydroquinone to reactive metabolites and suggest that the macrophage should be considered when assessing the hematopoietic toxicity of benzene.
- OSTI ID:
- 5153446
- Journal Information:
- Environmental Health Perspectives; (USA), Vol. 82; ISSN 0091-6765
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
BENZENE
TOXICITY
PEROXIDASES
ENZYME ACTIVITY
PHENOL
METABOLISM
QUINONES
BIOCHEMICAL REACTION KINETICS
CARBON 14 COMPOUNDS
DNA
ENZYME INHIBITORS
IN VITRO
MACROPHAGES
METABOLITES
MICE
MITOCHONDRIA
PROSTAGLANDINS
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
AROMATICS
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
ENZYMES
HYDROCARBONS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
OXIDOREDUCTASES
PHAGOCYTES
PHENOLS
REACTION KINETICS
RODENTS
SOMATIC CELLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques