Fluoride stimulation of microsomal benzene metabolism.

Benzene metabolism was examined in hepatic microsomes from male Sprague-Dawley rats. In addition to phenol, a highly polar unidentified component was formed. Fluoride, but not other halides, stimulated in vitro formation of both metabolites. Fluoride did not affect covalent binding of benzene metabolites to protein. Other mixed-function-oxidase reactions, and codeine and ethylmorphine demethylation and benzo[a]pyrene hydroxylation, were not affected by fluoride. The polar metabolite(s) was not retained on either a C-18 reverse-phase or a DEAE-Sephadex anion-exchange column. Thus, although highly polar, this component does not appear to be anionic. These results suggest that an enzyme with high specificity for benzene is responsible for microsomal benzene metabolism. Both phenol and the polar metabolite(s) appear to be formed through a common initial step, which is stimulated by fluoride.