title: Bromobenzene metabolism in vivo and in vitro. The mechanism of 4-bromocatechol formation.
abstract: The metabolism of bromobenzene has been examined in isolated hepatocytes and liver microsomes from phenobarbital-induced rats and in phenobarbital-induced rats in vivo. The metabolite profile produced upon incubation of isolated rat hepatocytes with bromobenzene differed with the hepatocyte concentration. At a low hepatocyte concentration (0.5 x 10(6) cells/ml), 4-bromophenol was the major metabolite, while at higher hepatocyte concentrations (2.0 and 5.0 x 10(6) cells/ml) bromobenzene-3,4-dihydrodiol was the major metabolite. 4-Bromophenol was the primary metabolite in incubations with rat liver microsomes. In vivo, 3- and 4-bromophenol were more predominant, with very little dihydrodiol formed. 4-Bromocatechol, a potentially toxic metabolite of bromobenzene, was formed in vivo as well as in isolated hepatocytes and microsomes. However, the mechanism of catechol formation differed, as determined by the retention of a deuterium label at the para position of bromobenzene. In microsomes, 4-bromophenol was the predominant precursor metabolite of 4-bromocatechol. In isolated hepatocytes, although the relative contribution of 4-bromophenol as the bromocatechol precursor differed with hepatocyte concentration, bromobenzene-3,4-dihydrodiol was the predominant precursor at all concentrations. In vivo, as in isolated hepatocytes, 4-bromocatechol was formed primarily via bromobenzene-3,4-dihydrodiol.
authors.affiliation: Department of Biochemical Toxicology, SRI International, Reno, NV.
authors.forename: N E
authors.initials: NE
authors.lastname: Miller
authors.forename: D
authors.initials: D
authors.lastname: Thomas
authors.forename: R E
authors.initials: RE
authors.lastname: Billings
mesh_terms: D000818:Animals; D001711:Biotransformation; D001969:Bromobenzenes / Q000378:metabolism*; D002396:Catechols / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001969:Bromobenzenes; D002396:Catechols; C040660:4-bromocatechol; C032036:bromobenzene; D010634:Phenobarbital