Diethylstilbestrol metabolic transformation in relation to organ specific tumor manifestation.

Oxidative biotransformation of the synthetic estrogen diethylstilbestrol (DES) gives rise to several reactive compounds. Two mechanisms are proposed concerning the possible involvement of reactive metabolites in the organotropic tumorigenesis of DES. The first mechanism suggests an affinity of the metabolite to the estradiol receptor present in estrogen target organs. This has been shown for the olefinic epoxide of DES. The second mechanism is based on the organ specific oxidation of DES by peroxidase. The intermediates of this reaction were found to bind to nucleic acid and protein in a manner characteristic of chemical carcinogens.