Is diethylstilbestrol bioactivated through peroxidase-mediated oxidation?
Metzler, M.; Mclachlan, J.A.
Journal of Environmental Pathology and Toxicology 1(4): 531-533
1978
ISSN/ISBN: 0146-4779 PMID: 722201 Document Number: 127173
The role of metabolism in the toxicity of estrogenic hormones is of current interest. The synthetic estrogen, diethylstilbestrol (DES), can be metabolized through oxidative pathways. Certain steps in this metabolic pathway have suggested potentially reactive intermediates. The conversion of DES to .beta.-dienestrol, a major urinary metabolite, was initially considered to proceed via a stilbene oxide intermediate. Alternatives to this proposed intermediate also should be considered. Another potentially reactive intermediate between DES and .beta.-dienestrol is proposed. The chemical oxidation of DES to dienestrol may proceed through a quinone. In biological systems, it is likely that a semiquinone may be an additional intermediate between DES and its quinone. Peroxidase-mediated oxidation of DES to the quinone may take place in estrogen target tissue. Both the quinone and semiquinone of DES may be reactive compounds. The formation in estrogen target tissues of reactive DES metabolites may enhance the organotropic toxicity of this compound. In addition, peroxidase-mediated oxidation may contribute to the toxicity of steroidal estrogens. The proposed bioactivation of DES may have general application to hormonal toxicity [e.g., in women].