Abstract
Biotransformation of styrene (ethenylbenzene) into styrene glycol (1-phenyl-1, 2-ethanediol) via styrene oxide (phenyloxirane), a mutagen and skin carcinogen, by rat liver microsomes in the presence of an NADPH-generating system has been investigated. Both metabolites were identified by gas-chromatography-mass spectroscopy. In the microsomal system, styrene oxide appeared only after a brief incubation and disapeared thereafter in spite of the continued formation of styrene glycol. This phenomenon was rationally interpreted on the basis of previously obtained evidence that during aerobic incubations, NADPH-dependent microsomal lipid peroxidation decreased P-450 activities selectively to a remarkable extent compared with epoxide hydratase activities. Addition of 3, 3, 3-trichloropropene oxide, a potent epoxide hydratase inhibitor, to the incubation medium prolonged the biological half-life of styrene oxide significantly, indicating one of major factors determining the biological level of the mutagen to be the relative ratio of these enzyme activities.
