Stereoselectivity of styrene oxidation in microsomes and in purified cytochrome P-450 enzymes from rat liver.

The stereochemistry of the cytochrome P-450(P-450)-dependent oxidation of styrene to styrene 7,8-oxide (SO) enantiomers was evaluated with rat hepatic microsomes and with individual rat liver P-450 enzymes in reconstituted monooxygenase systems. The stereoselectivity of the monooxygenase reaction with styrene was determined by high-performance liquid chromatographic analysis of the glutathione conjugates formed quantitatively from SO, the product of the monooxygenase reaction. Hepatic microsomes from control rats oxidized styrene at a rate of 13.1 +/- 4.5 nmol/min/nmol of P-450 and with a ratio of the amount of the (R)-styrene 7,8-oxide enantiomer to the amount of the (S)-styrene 7,8-oxide enantiomer (R/S) SO ratio of 0.65 +/- 0.1. These values were determined under incubation conditions in which epoxide hydrolase activity was inhibited by cyclohexene oxide, and at least 95% of the SO formed was converted enzymatically to glutathione conjugates. Treatment of rats i.p. with phenobarbital (PB) or beta-naphthoflavone (beta NF) caused changes in both parameters. Whereas the rates of oxidation in hepatic microsomes prepared from PB-treated rats was unchanged at 15.4 +/- 7.5 nmol/min/nmol of P-450 and decreased in hepatic microsomes from beta NF-treated rats to 9.4 +/- 2.8 nmol/min/nmol of P-450, the preference for formation of the R-enantiomer increased as the R/S ratio changed to 0.92 +/- 0.1 for PB and 1.25 +/- 0.1 for beta NF.(ABSTRACT TRUNCATED AT 250 WORDS)