1. The trans-epoxide of diethylstilboestrol and its pinacolone were synthesized chemically and the pinacolone shown to be formed from the epoxide by a non-enzymic process. 2. [14C]Diethylstiboestrol epoxide was converted by rat liver microsomal fraction into 4'-hydroxypropiophenone by a new type of cleavage reaction involving mono-oxygenase. Conditions for the formation of this metabolite and also water-soluble products were investigated together with the effect of inhibitors. A sex-difference in the conversion of diethylstilboestrol epoxide into 4'-hydroxypropiophenone and to polar and water-soluble products was observed. 3. Diethylstilboestrol epoxide was found to be a relatively stable compound that did not form a glutathione conjugate readily without further microsomal activation. A purified preparation of epoxide hydratase did not enhance its rate of conversion into the pinacolone. 4. Diethylstilboestrol epoxide was found to have about one-tenth the oestrogenic activity of diethylstilboestrol as measured by the increase in uterine weight or the induction of peroxidase in immature rat uteri. It was inactive as a mutagen when tested for its ability to inhibit bacteriophage phi X174 DNA viral replication. 5. The possible role of diethylstilboestrol epoxide as an intermediate in the metabolism of diethylstilboestrol and in mediating the harmful effects of this synthetic estrogen is discussed.

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