RT Journal Article
SR Electronic
T1 Bromobenzene metabolism in isolated rat hepatocytes. 18O2 incorporation studies.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 287
OP 295
VO 27
IS 2
A1 D Dankovic
A1 R E Billings
A1 W Seifert
A1 W G Stillwell
YR 1985
UL http://molpharm.aspetjournals.org/content/27/2/287.abstract
AB 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.