Catalysis of the oxidation and reduction reactions of steroid and stilbene estrogens by nuclear enzymes Article

Roy, D, Thomas, RD. (1994). Catalysis of the oxidation and reduction reactions of steroid and stilbene estrogens by nuclear enzymes . ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 315(2), 310-316. 10.1006/abbi.1994.1505

cited authors

  • Roy, D; Thomas, RD

authors

abstract

  • We demonstrated for the first time that nuclei were able to convert a stilbene estrogen (diethylstilbestrol) to reactive metabolites, which covalently bind to nuclear proteins and DNA. Depending on the cofactor used, nuclear enzymes catalyzed oxidation and/or reduction of stilbene and steroid estrogens. 2-Hydroxyestradiol (a major metabolite of steroidal estrogen, 17β-estradiol) and diethylstilbestrol (DES) were oxidized to 2, 3-estradiol quinone and DES quinone, respectively, by peroxide supported nuclear cytochromes P450. A Lineweaver-Burk plot of rate of formation of DES quinone at various substrate concentrations yielded a K(m) = 15 μM and V(max) = 10 nmol/mg protein/min. The oxidation of DES to DES quinone by nuclei was drastically decreased by known inhibitors of cytochromes P450. DES quinone was reduced back to DES by nuclei in the presence of NADPH, presumably through cytochrome P450 reductase. The reduction of DES quinone to DES by nuclei was significantly inhibited by antibodies and inhibitors of cytochrome P450 reductase. Under reaction conditions similar to oxidation of DES to DES quinone by nuclei, it was observed that nuclear metabolic products of DES were able to covalently bind to nuclear proteins and DNA. The data reported here establish that DES and a catechol estrogen can be oxidized to quinones and that the quinones may be reduced back to the hydroquinones by nuclear preparations when fortified with an appropriate cofactor and that reactive intermediates are involved based on observed covalent binding to macromolecules. The significance of these events, and their possible role in toxicity/cancer/teratogenicity, however, is not at all clear. © 1994 Academic Press, Inc.

publication date

  • January 1, 1994

published in

Digital Object Identifier (DOI)

start page

  • 310

end page

  • 316

volume

  • 315

issue

  • 2