Oxidative Metabolism of the Synthetic Estrogens Hexestrol and Dienestrol Indicates Reactive Intermediates

  • Manfred Metzler
  • John A. Mclachlan
Part of the Advances in Experimental Medicine and Biology book series (AEMB)


Although the molecular mechanisms of the transformation of normal cells to malignancy by chemical carcinogens are not understood as yet, it is generally assumed that a reactive electrophilic form of the chemical is required and that it initiates the tumorigenic event by binding covalently to critical cellular macromolecules, presumably DNA. Hormonal carcinogens are, on the other hand, usually considered to lack the capability for covalent binding. However, several laboratories have recently presented evidence that certain estrogens are metabolized to reactive forms, and DNA binding has been demonstrated both in vitro and in vivo (Blackburn et al., 1976, 1977; Tsibris and McGuire, 1977; Jaggi et al., 1978; Metzler and McLachlan, 1978a; Lutz, 1979; Okey and Nebert, 1979). Among those compounds were both steroid type estrogens such as estrone and ethinylestradiol as well as stilbene type estrogens such as diethylstilbestrol (DES).


Oxidative Metabolism Covalent Binding Olefinic Double Bond Arene Oxide Biliary Metabolite 
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Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Manfred Metzler
    • 1
  • John A. Mclachlan
    • 1
  1. 1.Institute of Pharmacology and ToxicologyUniversity of WürzburgWürzburgGermany

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