Diethylstilboestrol metabolism

Unsaturated aliphatic compounds and heterocyclic compounds may also be metabolized via epoxide intermediates as shown in Figure 4.6 and chapter 5, Figure 14. Note that when the epoxide ring opens, the chlorine atom shifts to the adjacent carbon atom (Fig. 4.6). In the case of the furan ipomeanol and vinyl chloride, the epoxide intermediate is thought to be responsible for the toxicity (see below and chap. 7). Other examples of unsaturated aliphatic compounds, which may be toxic and are metabolized via epoxides, are diethylstilboestrol, allylisopropyl acetamide, which destroys cytochrome P-450, sedormid, and secobarbital. 

Figure 6.28 Metabolism of diethylstilboestrol via an epoxide intermediate. This potentially reactive intermediate may show an affinity for the estradiol receptor and thereby accumulate in oestrogen target organs. This may facilitate reaction with DNA in these organs. Source. From Ref. 10.

When studied by a traditional, oestrogen-metabolism bioassay method, genistein was seen to be a very weak oestrogen. Its estrogenic potency was estimated at only 10 times the potency of diethylstilboestrol. 

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