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EMBARGOED FOR RELEASE: Fri., Jan. 23 BROADCAST EMBARGO: Thurs., Jan. 22, 4:00 p.m. EST
SEARCH CONTINUES FOR MECHANISM OF ESTROGEN-INDUCED CARCINOGENESIS Premarin metabolite is found to modify DNA
WASHINGTON -- A known metabolite of Premarin, the oldest and most widely-prescribed estrogen replacement therapy, has been found to attach to some of the basic building blocks of DNA, according to a report published January 23 in Chemical Research in Toxicology, a peer- reviewed journal of the American Chemical Society, the world's largest scientific society.
Although the results of this new study are very preliminary, they could help clarify the link between estrogen replacement therapies and breast cancer, the cause of which has yet to be established.
In a test-tube study done in the laboratory, Judy L. Bolton, Ph.D., and a research team at the University of Illinois at Chicago made 4-hydroxyequilenin (4-OHEN), one of the compounds produced in the body's degradation of Premarin. When they tested the reaction of 4-OHEN with deoxyguanidine, a primary component of DNA, they found that an unusual and unexpected compound was formed. "If this reaction were to occur with DNA in breast cells," Bolton says, "and that damage is not repaired, mutations could result, leading to the initiation of the carcinogenic process in the breast."
Bolton notes that "it is not known whether the same reaction occurs in humans, but given the direct link between long-term estrogen replacement therapy and the enhanced risk of breast cancer, the potential for the formation of these reactive metabolites from all of the estrogens in estrogen replacement formulations needs to be explored." Further work is in progress by the Bolton group.
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The article will appear on January 23 on the Web at http://pubs.acs.org/ (click on "Hot Articles" and access the Chemical Research in Toxicology link) and will appear in the February 16 issue of the journal's print edition.
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