Carcinogens Epoxide hydrase

Jerina, D. M., Dansette, P. M., Lu, A. Y. H., and Levin, W. Hepatic microsomal epoxide hydrase a sensitive radiometric assay for hydration of arene oxides of carcinogenic aromatic hydrocarbons. Mol. Pharmacol. (1977) 13 342-351. 

This epoxidation of AFB has been associated with aldrin epoxidase (AE) activity in trout (30). As with other epoxide carcinogens, OAFB may be a substrate 7or epoxide metabolizing enzyme systems such as epoxide hydrase (EH) (EC4.2.1.63) and glutathione-S-epoxide transferase (GTr) (EC4.4.1.7) found in mammals and fish (31, 32, 33, 34). AFB also undergoes a variety of other reactions, generally to less toxic metabolites depending on the species of animal involved (35, 36). The primary AFB metabolite in rainbow trout has been shown to be a reduced form of AFB, aflatoxicol (AFL) (24). 

Oesch, F. (1973) Mammalian epoxide hydrases Inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds. Xenobiotica. 3, 305-340... 

The metabolism of PAH compounds is mentioned here with benzo(a)pyrene as an example. Several steps lead to the formation of the carcinogenic metabolite product of benzo(a)pyrene. After an initial oxidation to form the 7,8-epoxide, the 7,8-diol is produced through the action of epoxide hydrase enzyme, as shown by the following reaction ... 

Electrostatic isopotential (EIP) minima186 often identify sites and ease of metabolism by epoxide hydrase, an enzyme responsible for the conversion of epoxides to diols by the addition of water. Molecular electrostatic potential energy calculations also are probably the best means of identifying positions of epoxidation and, possibly, metabolism in general. In the case of aflatoxin B for example, EIP maxima and minima calculated by the CNDO/2 method all lie close to the known sites of metabolism and, in particular, the formation of the carcinogenic 2,3-epoxide is readily predicted.189... 

P. Politzer and P. R. Laurence, Carcinogenesis, 5, 845 (1984). Relationships between the Electrostatic Potential, Epoxide Hydrase Inhibition, and Carcinogenicity for Some Hydrocarbon and Halogenated Hydrocarbon Epoxides. 

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