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Harmful chemicals may reprogram gene response to estrogen

New research shows that exposure to harmful chemicals and drugs during critical developmental periods early in life may actually "reprogram" the way certain genes respond to the female hormone estrogen. This genetic reprogramming may determine whether people with a genetic predisposition for a disease actually develop the disease.

The new research shows that when rats with a genetic predisposition to uterine tumors also receive an early-life exposure to diethylstilbestrol (DES), a synthetic form of estrogen linked to vaginal cancer, the incidence of uterine tumors rises to almost 100 percent. By comparison, slightly more than half of the unexposed animals, those having only the genetic defect, developed the uterine tumors.

DES is a drug that was prescribed for women from 1938 to 1971 to prevent miscarriages and premature deliveries. Daughters of women who used DES are at increased risk for reproductive tract abnormalities, pregnancy complications such as ectopic pregnancies and preterm deliveries, infertility, and a rare vaginal and cervical cancer called clear-cell adenocarcinoma. Other research conducted by NIEHS scientists indicates that women exposed to DES in utero have a higher risk of uterine fibroids.

The National Institute of Environmental Health Sciences, a component of the National Institutes of Health, provided funding to researchers at the University of Texas M.D. Anderson Cancer Center for the two-year study. The study results will be published in the May 2005 issue of the Proceedings of the National Academy of Sciences.

The discovery is important because it changes conventional thinking about the way in which genetic predisposition and things in the environment interact to increase disease risk. Until now, scientists thought that exposure to harmful agents in the environment caused damage to the gene. This study, however, indicates that an environmental agent can actually change or reprogram the gene so that it function
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Contact: John Peterson
peterso4@niehs.nih.gov
919-541-7860
NIH/National Institute of Environmental Health Sciences
31-May-2005


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