Bromobenzene metabolism in isolated rat hepatocytes. 18O2 incorporation studies.
Bromobenzene metabolites have been determined in incubations of hepatocytes isolated from untreated, phenobarbital-treated, and beta-naphthoflavone-treated rats. The total formation of bromobenzene metabolites was increased 9-fold in incubations with hepatocytes isolated from phenobarbital-treated rats, and the percentage of total metabolites recovered as bromobenzene-3,4-dihydrodiol and 4-bromocatechol was more than doubled, compared to incubations using hepatocytes from untreated rats. The formation of 2-bromophenol and bromobenzene-2,3-dihydrodiol was increased more than 10-fold in incubations of hepatocytes from beta-naphthoflavone-treated rats, as compared to those of hepatocytes from untreated rats, but recovery of 4-bromocatechol was unchanged. The mechanism of 4-bromocatechol formation from bromobenzene was investigated by examining the incorporation of 18O from 18O2 and H218O into 4-bromocatechol during incubations of bromobenzene with hepatocytes from untreated and phenobarbital-treated rats. Potential metabolic precursor molecules of 4-bromocatechol were also incubated individually with isolated hepatocytes, in order to clarify their roles in 4-bromocatechol formation. The results of these studies show that 4-bromocatechol is formed in intact cells almost exclusively from bromobenzene-3,4-dihydrodiol, rather than from the bromophenols. The bromophenols are, instead, mostly conjugated. The rapid and extensive conjugation of the bromophenols by intact cells may restrict their role as precursors of 4-bromocatechol, while bromobenzene 3,4-dihydrodiol is well converted into 4-bromocatechol by hepatocytes.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D001969:Bromobenzenes / Q000378:metabolism*; D002396:Catechols / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010103:Oxygen Isotopes; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D001969:Bromobenzenes; D002396:Catechols; D010103:Oxygen Isotopes; D019324:beta-Naphthoflavone; C032036:bromobenzene; D010634:Phenobarbital