title: A stable epoxide as a potential endogenous estrogen metabolite: Possible significance in breast cancer?
abstract: Epoxides as reactive intermediates of estrogen metabolism have been considered to be potential precursors of the 2- and 4-hydroxy, catechol estrogens and even to be mutagenic/carcinogenic agents themselves. The labile nature of the intermediates has made proof of their existence difficult in natural biological conditions. In our studies on estrogen metabolism in vitro, in various tissues from several laboratory and domestic species, there was chromatographic evidence of formation of a stable estrogen metabolite that could be seen after incubation with radiolabeled estrone, but not with unlabeled substrate. Investigation with acid treatment of the metabolite yielded material detected as 6-hydroxy-estrone-suggesting the presence of an additional oxygen atom in the molecule. An identification of the "unknown compound" has not yet been made but, with this evidence, the properties revealed so far can best be met by assuming the presence of 5,6-epoxy-estrone. The recent favorable reports on the role of 5α,6α-epoxy-cholesterol in breast cancer has led to the hypothesis that the formation of a similar, stable epoxide of an estrogen could potentially be a compound of interest. If a metabolic pathway from estrone to 6-hydroxy-estrone through a stable epoxide has indeed been observed, it would suggest that identifying and screening for the enzymes responsible for its production, as opposed to those generating the catecholestrogens, could provide valuable information in relation to breast cancer. The balance in production of estrogen epoxides could be a key factor in determining normal health or risk of tumor development.
authors.affiliation: Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada. Electronic address: jraeside@uoguelph.ca.
authors.forename: James I
authors.initials: JI
authors.lastname: Raeside
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D002273:Carcinogens / Q000737:chemistry; D002845:Chromatography; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015674:Mammary Neoplasms, Animal / Q000378:metabolism; D051379:Mice; D008962:Models, Theoretical; D009153:Mutagens / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D012306:Risk
chemical_list: D002273:Carcinogens; D004852:Epoxy Compounds; D004967:Estrogens; D006894:Hydroxyestrones; D009153:Mutagens; C040162:6-hydroxyestrone; D003577:Cytochrome P-450 Enzyme System; D010100:Oxygen