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...

BACKGROUND The aim of this study was to investigate the effect of two genetic polymorphisms in the coding regions (exon 3 and exon 4) of the EPHX1 gene, ie, 337T>C and 416A>G, respectively, on the metabolism of carbamazepine (CBZ) 10,11-epoxide (the active metabolite of CBZ) by evaluating the variation in serum CBZ 10,11-epoxide levels 4 hours after administration of the drug. Moreover, we repo...

Synthetic studies on the antibiotic natural product ripostatin A have been carried out with the aim to construct the C9-C10 bond by a nickel(0)-catalyzed coupling reaction of an enyne and an epoxide, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. A cyclopropyl enyne fragment corresponding to C1-C9 has been synthesized in high yield...

From our recent work on the three-dimensional structure of epoxide hydrolases we theoretically deduced the likelihood of a two-step catalytic mechanism that we and others have subsequently experimentally confirmed. Analysis of the rate of the two steps by us and by others show that the first step-responsible for removal of the reactive epoxide from the system-works extraordinarily fast (typical...