Epoxide hydrolase (EH) enzymes catalyze the hydration of racemic epoxides to yield their corresponding vicinal diols. These enzymes present different enantio- and regioselectivity depending upon either the substrate structure or the substitution pattern of the epoxide ring. In this study, we computationally investigate the Bacillus megaterium epoxide hydrolase (BmEH)-mediated hydrolysis of race...

RNA was isolated by a phenol extraction method from mouse embryo cells treated in culture with either [G-3H]-7-methylbenz(a)anthracene or [G-3H]-7-methylbenz(a)anthracene 5,6-oxide (the K-region epoxide). The RNA was degraded to ribonucleosides, mixed with ultraviolet-absorbing quantities of the epoxide ribonucleoside products isolated from RNA that had reacted with 7-methylbenz(a)anthracene 5,...

RNA was isolated by a phenol extraction method from mouse embryo cells treated in culture with either [G-~H]-7 methylbenz[a]anthracene or [G-:'H]-7-methylbenz[a]anthracene 5,6-oxide (the K-region epoxide). The RNA was degraded to ribonucleosides, mixed with ultraviolet-absorbing quantit ies of the epoxide ribonucleoside products isolated from RNA that had reacted with 7-methylbenz[a]anthracene ...

The soluble epoxide hydrolase (sEH) plays a significant role in the biosynthesis of inflammation mediators as well as xenobiotic transformations. Herein, we report the discovery of substituted ureas and carbamates as potent inhibitors of sEH. Some of these selective, competitive tight-binding inhibitors with nanomolar K(i) values interacted stoichiometrically with the homogenous recombinant mur...

The mutagenic activities of the enantiomers of the pair of diastereomeric bay-region benzo(c)phenanthrene 3,4-diol-1,2epoxides were evaluated in histidine-dependent strains of Sal monella typhimurium and in an 8-azaguanine-sensitive Chinese hamster Å“il line. In strains TA 98 and TA 100 of S. typhimurium, the range in mutagenic activity observed for the four optically active isomers was less th...

Biosynthesis of the leukotriene A (LTA) class of epoxide is a lipoxygenase-catalyzed transformation requiring a fatty acid hydroperoxide substrate containing at least three double bonds. Here, we report on biosynthesis of a dienoic analog of LTA epoxides via a different enzymatic mechanism. Beginning with homolytic cleavage of the hydroperoxide moiety, a catalase/peroxidase-related hemoprotein ...

The exo isomer of aflatoxin B1 (AFB1) 8,9-epoxide appears to be the only product of AFB1 involved in reaction with DNA and reacts with the N7 atom of guanine via an SN2 reaction from an intercalated state. Although the epoxide hydrolyzes rapidly in H2O (0.6 s-1 at 25 degrees C), very high yields of DNA adduct result. Experimental binding data were fit to a model in which the epoxide forms a rev...

The mutagenic activity of benzo(c)phenanthrene and some of its known and potential metabolites was evaluated in bac terial and mammalian cells either in the presence or absence of a metabolic activation system. trans-3,4-Dihydroxy-3,4-di hydrobenzo(c)phenanthrene [benzo(c)phenanthrene 3,4-di hydrodiol] was metabolized by a cytochrome P-450-dependent monooxygenase system to products which were s...

Benzo(a)anthracene (BA) and several benzo-ring deriv atives of BA were tested for their tumor-initiating activity on mouse skin. A single topical application of 0.1 to 2.0 /<mol of hydrocarbon was followed 7 days later by twiceweekly applications of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate for 20 weeks. Comparisons of the percentage of mice with papillomas and the number of papil...

With 8-(14)C-styrene oxide as substrate, specific glutathione S-transferase and epoxide hydrase activities were determined in subcellular fractions of liver, lungs, kidney, and intestinal mucosa from rabbit, rat, and guinea pig. Liver had the highest enzyme activities in each species. Rat and guinea pig had higher glutathione S-transferase activity in both liver and kidney than rabbit. Rat test...