Search results for "Epoxide Hydratase"
showing 5 items of 5 documents
Prevention of benzo(a)pyrene-induced mutagenicity by homogeneous epoxide hydratase
1976
Benzo(a)pyrene and benz(a)anthrancene which, in contrast to the K-region epoxides benzo(a)pyrene 4,5-oxide and benz(a)anthracene 5,6-oxide, are not mutagenic to Salmonella typhimurium TA 1537 in the absence of mammalian enzyme preparations, were activated by liver microsomes from C3H mice, which had not received any pretreatment, to mutagens reverting this tester strain to histidine prototrophy. Addition of epoxide hydratase inhibitors greatly increased this mutagenicity and addition of pure epoxide hydratase reduced it by more than 95% down to the range of spontaneous mutations as observed in absence of any added mutagen. This demonstrates that the metabolic pathway responsible for the mut…
Dual role of epoxide hydratase in both activation and inactivation of benzo(a)pyrene.
1977
The effect of epoxide hydratase upon the mutagenicity of benzo(a)pyrene was investigated using two Salmonella typhimurium strains (TA 1537 and TA 98). These two bacterial strains were found to differ characteristically in their susceptibility to different mutagens biologically produced from benzo(a)pyrene providing a diagnostic tool to investigate which types of mutagenic metabolites were produced in various metabolic situations. The results showed that the pattern of mutagenic metabolites produced by microsomes from methylcholanthrene-treated mice was very different from that produced by microsomes from phenobarbital-treated or untreated mice. However in all cases at least two mutagenic me…
Radioactively labelled epoxides part II. (1) tritium labelled cyclohexene oxide, transstilbene oxide and phenanthrene 9,10-oxide
1980
Tritium labelled cyclohexene oxide, trans-stilbene oxide and phenanthrene 9,10-oxide were prepared with specific activities of 0.7 - 1.1 mCi per mmole starting with monoor diketo compounds. Tritium was introduced by reducing the ketone precursors with tritiated complex metal hydrides. The resulting alcohols were transformed to the epoxides by methods described for the unlabelled compounds. The syntheses require only two or three steps and yield cyclohexene oxide, trans-stilbene oxide and phenanthrene 9,10-oxide, important substrates for the study of epoxide hydratase and glutathione S-transferases in high radiochemical purity.
Dihydrodiol Dehydrogenase: An Important Enzyme in Dihydrodiol-Epoxide Pathway — Mediated Benzo(A)Pyrene Mutagenicity
1978
Benzo(a)pyrene is metabolized to two major groups of mutagenically reactive metabolites: Monofunctional epoxides and dihydrodiol-epoxides. Various monooxygenase forms catalyze the various pathways at very different rates. In metabolic situations where the contribution by dihydrodiol-epoxides is small, epoxide hydratase represents a very efficient protective system. However, in situations where the mutagenic effect is predominately due to dihydrodiol-epoxide, the effect of epoxide hydratase is complicated and weak. We have now obtained evidence that a dihydrodiol dehydrogenase represents an efficient protective system in the latter situation. The enyzme was purified to homogeneity and the pu…
Enzymes as Regulators of Toxic Reactions by Electrophilic Metabolites
1979
Conversion of many compounds which are not electrophilically reactive as such to metabolites responsible for cytotoxic, mutagenic and/or carcinogenic effects is catalyzed by mammalian enzymes. Many reactive agents, whether metabolites or parent compounds, are also subject to inactivation by mammalian enzymes.