METABOLISM OF STYRENE OXIDE TO STYRENE GLYCOL BY MOUSE-LIVER AND LUNG

Styrene is a widely used chemical that causes both liver and lung dama ge in mice. Strain and sex differences in susceptibility to styrene-in duced toxicity have been reported. Understanding the relationship of t he metabolism of styrene to its toxicity depends upon knowing the bala nce between the bioactivation of styrene to the epoxide by cytochromes P-450 and the detoxication of the oxide to the glycol by microsomal e poxide hydrolase. When hepatic and pulmonary microsomal preparations f rom non-Swiss albino (NSA) and Swiss (CD-1) mice were compared for the ir abilities to metabolize racemic, S-and R-styrene oxide to styrene g lycol, enzymic activities were higher in liver than in lung. R-Styrene glycol formation was favored with racemic styrene oxide as the substr ate. Only minor strain differences were found that could not account f or the differences in reported susceptibility to styrene-induced toxic ity. While the oxidation of styrene to styrene oxide was similar in ma le and female NSA mice, male hepatic microsomes were more active in th e metabolism of the oxide to the glycol. Hepatic metabolism of styrene oxide to styrene glycol was inducible by butylated hydroxyanisole, wh ereas pulmonary metabolism was not. The data indicate that strain diff erences in susceptibility cannot be accounted for by this detoxication step, and there are sex differences in this reaction.