Previous studies in our laboratory indicated that phenobarbital treatment of rats caused a significant increase in both 2,3- and 3,4-epoxidation of bromobenzene in their hepatic microsomes and that 3-methylcholanthrene or β-naphthoflavone caused a selective increase in the 2,3-epoxidation pathway. Sodium dodecyl sulfate, polyacrylamide gel electrophoresis of microsomes revealed multiple forms of cytochrome P-450, in keeping with the notion that different species of the heme protein catalyzed the 'nontoxic' 2,3-epoxidation and the 'toxic' 3,4-epoxidation of this environmental chemical. The present study describes the metabolism of bromobenzene with highly purified cytochrome P-450 and P-448 isolated from rabbit hepatic microsomal preparations. This study involved the enzymatic conversion of bromobenzene to o-bromophenol via 2,3-epoxidation and p-bromophenol via 3,4-epoxidation in a reconstituted mixed-function oxygenase system. Evidence is presented that purified rabbit cytochrome P-450 (LM2) prepared from animals treated with phenobarbital specifically catalyzes the 3,4-epoxidation of bromobenzene to p-bromophenol. Furthermore, evidence is given that purified rabbit cytochrome P-448 (LM4) prepared from animals treated with β-naphthoflavone specifically catalyzes the 2,3-epoxidation of bromobenzene to o-bromophenol. These data represent an interesting example of two epoxidation pathways involved in the metabolism of a common substrate, one of which leads to cellular damage, i.e., phenobarbital-inducible 3,4-epoxidation; the other, i.e., β-naphthaoflavone-inducible 2,3-epoxidation of bromobenzene, is not particularly detrimental. Each epoxidation pathway preferentially requires a different and specific form of the heme protein.
|Original language||English (US)|
|Number of pages||2|
|Publication status||Published - 1981|
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