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Metabolism of stilbene estrogens and steroidal estrogens in relation to carcinogenicity

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Abstract

The oxidative metabolism of diethylstilbestrol (DES) and 17α-ethynyl estradiol, as examples of stilbene- and steroid-type estrogens, is discussed with respect to the formation of reactive intermediates. For DES, a genotoxic potential is implied by metabolic studies and positive effects in short-term tests for genetic damage. A particularly important pathway for DES carcinogenicity appears to be peroxidase-mediated oxidation. Although data for steroidal estrogens are more ambiguous, the available evidence suggests that metabolic activation by peroxidatic oxidation may also be of importance for this class of estrogens.

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Abbreviations

DES:

diethylstilbestrol, 3,4-bis-(p-hydroxyphenyl)hex-3-ene

E-DES:

trans-diethylstilbestrol

Z-DES:

cis-diethylstilbestrol

DIES:

dienestrol, 3,4-bis-(p-hydroxyphenyl)-hexa-2,4-diene (nomenclature of DES metabolites according to the system of Metzler and McLachlan 1978a)

E1 :

estrone

E2 :

estradiol-17ß

EE2 :

17α-ethynylestradiol

7,8-BF:

7,8-benzoflavone

GC:

gas chromatography

HPLC:

high performance liquid chromatography

MS:

mass spectrometry

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  1. Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Strasse 9, D-8700, Würzburg, Germany

    Manfred Metzler

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Metzler, M. Metabolism of stilbene estrogens and steroidal estrogens in relation to carcinogenicity. Arch Toxicol 55, 104–109 (1984). https://doi.org/10.1007/BF00346047

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  • DOI: https://doi.org/10.1007/BF00346047

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