Role of 4-bromophenol and 4-bromocatechol in bromobenzene covalent binding and toxicity in isolated rat hepatocytes

Journal Article · Sun Jun 30 04:00:00 EDT 1985 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(85)90354-0· OSTI ID:5018620

Dankovic, D A; Billings, R E

4-Bromophenol and 4-bromocatechol are formed as metabolites of bromobenzene in vivo and in isolated rat hepatocytes. Both of these metabolites may potentially contribute to the hepatotoxicity of bromobenzene. Bromobenzene metabolism in hepatocytes isolated from phenobarbital-treated rats forms 0.12 to 0.17 mM 4-bromophenol and 4-bromocatechol in 2 hr, with 1 to 3 mM bromobenzene. The role of activated metabolites derived from 4-bromophenol and 4-bromocatechol in bromobenzene covalent binding and toxicity was investigated with isolated hepatocytes in suspension. The covalent binding of the phenol and the catechol was increased four- to eightfold by the addition of unlabeled bromobenzene. Two-hour incubations of 0.25 mM /sup 14/C-labeled 4-bromophenol or 4-bromocatechol with hepatocytes isolated from phenobarbital-treated rats resulted, under these conditions, in no significant toxicity, and approximately 4 and 25%, respectively, of the covalent binding associated with bromobenzene itself. Two- and six-hour incubations with higher 4-bromophenol and 4-bromocatechol concentrations demonstrated that 1 to 3 mM substrate concentrations were required for cytotoxicity. These results show that metabolically produced 4-bromophenol and 4-bromocatechol do not play significant roles in the production of bromobenzene cytotoxicity in isolated hepatocytes, and that they contribute only modestly to bromobenzene covalent binding.

• OSTI ID: 5018620
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 2; ISSN TXAPA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANESTHETICS
ANIMAL CELLS
ANIMALS
ANTICONVULSANTS
AROMATICS
AZINES
BARBITURATES
BENZENE
BIOCHEMICAL REACTION KINETICS
CARBON 14 COMPOUNDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
COVALENCE
DEVELOPERS
DRUGS
ENZYMES
GLUTATHIONE
HEMIACETAL DEHYDROGENASES
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
HYPNOTICS AND SEDATIVES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LACTATE DEHYDROGENASE
LIVER CELLS
MAMMALS
METABOLISM
METABOLITES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
PEPTIDES
PHENOBARBITAL
PHENOLS
POLYPEPTIDES
POLYPHENOLS
PROTEINS
PYRIMIDINES
PYROCATECHOL
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RODENTS
SOMATIC CELLS
TOXICITY
TRACER TECHNIQUES
VERTEBRATES