PT  - JOURNAL ARTICLE
AU  - N E Miller
AU  - D Thomas
AU  - R E Billings
TI  - Bromobenzene metabolism in vivo and in vitro. The mechanism of 4-bromocatechol formation.
DP  - 1990 May 01
TA  - Drug Metabolism and Disposition
PG  - 304--308
VI  - 18
IP  - 3
4099  - http://dmd.aspetjournals.org/content/18/3/304.short
4100  - http://dmd.aspetjournals.org/content/18/3/304.full
SO  - Drug Metab Dispos1990 May 01; 18
AB  - 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.