Induction of hepatic mono-oxygenase systems of pregnant rats with phenobarbital and 3-methylcholanthrene.
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Aniline Compounds↗
Biomedical subjects
T M Guenthner
Publications and source records attributed to T M Guenthner.
Hydrolysis of the 2',3'-allylic epoxides of allylbenzene, estragole, eugenol, and safrole by both microsomal and cytosolic epoxide hydrolases.
2',3'-Allylic epoxide derivatives of allylbenzene and its analogs estragole, eugenol, and safrole were synthesized, and their enzymatic conversion to dihydrodiols by cytosolic and microsomal epoxide hydrolases was examined. All four epoxides were good substrates for both epoxide hydrolases, with Michaelis constants in the low micromolar range. Two putatively selective inhibitors of cytosolic and microsomal epoxide hydrolases, trichloropropylene oxide and nordihydroguaiaretic acid, were used to inhibit the hydrolysis of these allylic epoxides. Minimal selectivity toward either hydrolase was seen with either inhibitor, suggesting that the "selectivity" of these inhibitors is highly substrate-dependent. The susceptibilities of these epoxides to rapid hydrolysis by both epoxide hydrolases may explain their low genotoxic potencies in vivo.
Allylbenzene Derivatives↗
Multiple epoxide hydrolases in human lung.
Benzo(a)pyrene 4,5-oxide (BPO) hydrolase activity and trans-stilbene oxide hydrolase activity were measured in human lung samples obtained from 12 different patients. These activities, attributable to different epoxide hydrolases, were both found in significant amounts in the cytosolic as well as the microsomal cell fractions. The catalytic properties of human lung BPO hydrolases were further investigated, and similarities between the cytosolic and microsomal forms of this enzyme were noted. Similar Km values were found for both forms (22 microM for the microsomal enzyme, 37 microM for the cytosolic enzyme). Both forms responded in similar fashion to a number of enzyme inhibitors in vitro, and the IC50 values for each inhibitor were the same for both forms. Both forms of the enzyme were inhibited uncompetitively by trichloropropene oxide, and the Kii value for the cytosolic hydrolase (11 microM) was similar to that obtained for the microsomal hydrolase (15 microM). These two forms of BPO hydrolase in the human lung are very similar, possibly identical, enzymes.
Benzopyrenes↗
Detoxication of the 2',3'-epoxide metabolites of allylbenzene and estragole. Conjugation with glutathione.
The enzymatic detoxication in vitro of the 2',3'-epoxide derivatives of allylbenzene and estragole was examined, and the relative rates of enzymatic glutathione conjugation and epoxide hydrolysis were compared with those for styrene 1',2'-oxide. HPLC was used to determine the amounts of dihydrodiol and glutathione conjugate metabolites formed by cell extracts from several sources. Although some differences among species were observed, in general, the rates of epoxide inactivation by both pathways are similar. We conclude that one explanation for the apparent lack of genotoxicity of these allylic epoxides in vivo may be their rapid metabolic inactivation by both glutathione S-transferases and epoxide hydrolases, which occur to approximately equal degrees in vitro.
Allylbenzene Derivatives↗