Hepatic microsomal epoxidation of bromobenzene to phenols and its toxicological implication

Abstract

In vitro microsomal hepatic epoxidation of bromobenzene in rats and mice is presented in this study. Formation of o-bromophenol via bromobenzene-2,3-epoxide and p-bromophenol via bromobenzene-3,4-epoxide was assayed enzymatically and identified by a new, rapid and sensitive gas-liquid chromatography method using electron capture detection. Pretreatment of the animals with phenobarbital caused significant increases in both pathways whereas 3-methylcholanthrene or [beta]-naphthoflavone caused a selective and marked increase of only the 2,3-epoxide pathway. Sodium dodecyl sulfate-gel electrophoresis of microsomal preparations resolved multiple forms of cytochrome P-450 and indicated that different forms of the heme protein were responsible for the formation of o-bromophenol and p-bromophenol. it is of interest that various inducers augment particular pathways for a common substrate especially since bromobenzene-3,4-epoxide and not the bromobenzene-2,3-epoxide has been proposed as the cytotoxic reactive metabolite of bromobenzene.