Potential endogenous epoxides of steroid hormones: initiators of breast and other malignancies?
The metabolism of steroid hormones has the potential for generating labile and reactive intermediates that may themselves be mutagenic and/or carcinogenic. Epoxides, derived from the cytochrome P450s, offer that potential and the concept is derived from extensive metabolic knowledge of PAHs and other compounds. In the case of the estrogens, possible epoxides have been proposed as metabolic precursors in the formation of the catechol estrogens. One of these compounds is the first structure shown below that has been demonstrated to be as carcinogenic as 3-methylcholanthrene. Increasingly, there is evidence that some, of these epoxides are intermediates in estrogen metabolism. If that were the case, individuals could be screened for their proclivity to produce such carcinogens and therapies may be designed to inhibit their formation.
Soloway
Albert H
AH
College of Pharmacy, Division of Medicinal Chemistry, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, United States. soloway.1@osu.edu
D001943:Breast Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D002273:Carcinogens; D004247:DNA / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry*; D004958:Estradiol / Q000737:chemistry; D004967:Estrogens / Q000378:metabolism; D020249:Hormone Replacement Therapy / Q000379:methods; D006728:Hormones / Q000737:chemistry*; D006801:Humans; D008748:Methylcholanthrene / Q000494:pharmacology; D008954:Models, Biological; D008956:Models, Chemical; D008962:Models, Theoretical; D013256:Steroids / Q000737:chemistry*
D002273:Carcinogens; D004852:Epoxy Compounds; D004967:Estrogens; D006728:Hormones; D013256:Steroids; D004958:Estradiol; D008748:Methylcholanthrene; D004247:DNA