Specificity of mouse liver cytosolic epoxide hydrolase for K-region epoxides derived from polycyclic aromatic hydrocarbons.

Mouse liver cytosol epoxide hydrolase, known to be very active for certain alkene oxides, had a specific activity which was 2.1-, 11- and 160-fold lower than that of the microsomal epoxide hydrolase for the arene oxides 7-methylbenz[a]anthracene 5,6-oxide, benz[a]anthracene 5,6-oxide and phenanthrene 9,10-oxide, respectively. For benzo[a]pyrene 4,5-oxide no activity (less than 10 pmol product/mg protein/min) of cytoplasmic epoxide hydrolase was detectable. The specific activity of cytoplasmic epoxide hydrolase was much lower for all K-region epoxides investigated, compared to trans-stilbene oxide used as a positive control and for which a new assay is described. It is concluded from these rates combined with the fact that these lipophilic K-region epoxides are expected to stay preferentially at membranous sites where they are generated, that cytoplasmic epoxide hydrolase plays a minor role for their transformation compared to membrane-bound hydrolase. The data also show that for the substrates investigated the epoxide hydrolase activities in the cytoplasmic and microsomal fractions are complementary to some extent, but there is no quantitative inverse relationship.