Oesch F
Arzneimittelforschung. 1977;27(96):1832-5.
An in vitro test system was used to study the relative contribution of epoxides metabolically produced from aromatic or olefinic drugs to the total of mutagenically reactive metabolites. As an epoxide-specific tool the enzyme epoxide hydratase was purified to homogeneity. Using several aromatic and olefinic hydrocarbons as model substrates the following was observed, exceptions being discussed in the main text: 1. Epoxides represent the most important and generally the almost exclusive metabolites responsible for the observed toxic endpoint. 2. These epoxides generally are efficiently inactivated by epoxide hydratase. The rather narrow limitations of exceptions are outlined in detail. 3. Amongst the enzymes metabolizing epoxides, for the substrates investigated epoxide hydratase represents the system which is most critical for the control of tissue levels of epoxides. 4. Several practical consequences following from these facts are outlined in the last paragraph of this paper. 5. A generalization from these model experiments will be justified only after further experimental validation.
采用体外测试系统研究了芳香族或烯烃类药物代谢产生的环氧化物对致突变活性代谢物总量的相对贡献。作为一种环氧化物特异性工具，环氧水解酶被纯化至同质。以几种芳香烃和烯烃作为模型底物，观察到以下情况（正文将讨论例外情况）：1. 环氧化物是导致所观察到的毒性终点的最重要且通常几乎是唯一的代谢物。2. 这些环氧化物通常能被环氧水解酶有效灭活。详细概述了例外情况的相当狭窄的局限性。3. 在代谢环氧化物的酶中，对于所研究的底物，环氧水解酶是控制组织中环氧化物水平最关键的系统。4. 本文最后一段概述了这些事实带来的几个实际后果。5. 只有经过进一步的实验验证，才能从这些模型实验中得出一般性结论。
