BROMOBENZENE METABOLISM IN ISOLATED RAT HEPATOCYTES - O-18(2) INCORPORATION STUDIES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 27  (2) , 287-295
Abstract
Bromobenzene metabolites were 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. 4-Bromocatechol is formed in intact cells almost exclusively from bromobenzene 3,4-dihydrodiol, rather than from the bromophenols. The bromophenols are, 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.