Hepatic microsomal epoxidation of bromobenzene to phenols and its toxicological implication.

Hepatic Microsomal Epoxidation of Bromobenzene to Phenols and Its Toxicological Implication. LAU, S. S. AND ZANNONI, V. G. (1979). Toxicol. Appl. Pharmacol. 50, 309318. 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 b-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.