Stimulation of mammalian epoxide hydrase activity by flavones.

1. A series of flavones have been examined for the ability to stimulate the activity in vitro of rat liver microsomal epoxide hydrase. Flavone and 7,8-benzoflavone both stimulate epoxide hydrase activity in vitro with styrene oxide as the substrate. The stimulation by flavone itself was several times that of 7,8-benzoflavone. 2. When tested in vitro under the same conditions, the stimulation by 7,8-benzoflavone was significantly greater than the stimulation by metyrapone, a recognized stimulator of the activity of epoxide hydrase in vitro. The stimulation by 6,7-benzoflavone was barely detectable; the 5,6-benzoflavone isomer did not stimulate epoxide hydrase activity. 3. Exposure of rate to either 7,8- or 5,6-benzoflavone for 4 days before killing did not increase the epoxide hydrase specific activity in the subsequently isolated microsomes. Exposure to flavone, however, did induce epoxide hydrase activity. 4. The possible relevance of these observations to the effects of benzoflavone upon arylhydrocarbon-induced tumours is discussed.