PMID: 9558716Apr 29, 1998Paper

Estrogen-dependent gene regulation by an oxidative metabolite of diethylstilbestrol, diethylstilbestrol-4',4"-quinone

Steroids
K ChaeK S Korach

Abstract

Diethylstilbestrol (DES) is a well-characterized carcinogen in humans and animals although its mechanisms of carcinogenicity are not yet known. While the estrogenic activity of DES is important, there is evidence that oxidative metabolism also plays an important role for its toxicity. DES is oxidatively metabolized in vivo and in vitro to a number of compounds including diethylstilbestrol-4',4"-quinone (DQ), an unstable and reactive intermediate, and Z,Z-dienestrol (ZZ-DIEN). Estrogen receptor (ER) binding assays with mouse uterine cytosol indicate that DES, DQ and ZZ-DIEN have relative binding affinities of 286, 3.6 and 0.3, respectively, relative to estradiol as 100. In addition, DQ binds irreversibly and specifically to ER suggesting that DQ may be biologically active despite its rapid metabolism and lower binding affinity compared to DES. To test this, COS-1 cells were transfected with an estrogen responsive reporter construct containing of VitA2 estrogen response element (ERE) with or without an ER expression vector. In the presence of ER, treatments with DES, DQ and ZZ-DIEN resulted in 11, 10, and 2-fold induction of chloramphenicol acetyltransferase (CAT) activity, respectively. This induction was mediated by estrogen re...Continue Reading

References

Jan 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·K S KorachJ A McLachlan
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Citations

Jul 9, 2004·Toxicology and Applied Pharmacology·Kimberly P MillerJodi A Flaws
May 14, 2005·Mutation Research·Heidrun Ellinger-ZiegelbauerHans Juergen Ahr
Sep 25, 2003·In Vitro Cellular & Developmental Biology. Animal·Tomohiro UmezuYasuhiro Tomooka

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