Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Harmful chemicals may reprogram gene response to estrogen

31.05.2005


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 functions differently.

"This study is telling us that an environmental reprogramming of a normal response, combined with an inherited gene defect, work together to promote cancer," said NIEHS Director David Schwartz, M.D. "If this model is correct, it will help doctors to determine which individuals are more likely to develop cancers of the uterus, breast and prostate."

The finding should alert doctors to ask more questions about a patient’s early-life exposures to chemicals and other harmful agents in order to better predict that person’s cancer risk.

"Most people with a family history for a particular disease are concerned about their recent exposures to harmful agents in the environment," said Cheryl Walker, Ph.D., professor of molecular carcinogenesis at the M.D. Anderson Cancer Center and lead author on the study. "We are just beginning to realize that exposures received decades earlier, during critical developmental stages, may be much more important in determining who develops cancer as an adult."

The researchers used a special strain of rats with a defect in a gene called Tsc-2 (tuberous sclerosis complex 2) that made them more susceptible to uterine leiomyomas, benign tumors that are common in women over 30 years of age. These rats were then treated with DES during days 3, 4 and 5 of life, during a critical period of uterine development.

Once the rats reached adulthood, almost 95 percent had developed the uterine tumors. Furthermore, the tumors were much larger and more numerous than those in genetically defective rats not receiving the DES treatment. "These data suggest that environmental exposures during development of the uterus can interact with a preexisting genetic susceptibility to increase the risk of disease," said Walker. "We are looking at a new kind of gene-environment interaction that determines who gets cancer and who doesn’t."

According to Walker, the increase in frequency and size of the uterine tumors is due to DES’ ability to influence estrogen, a female hormone that is involved in promoting the growth of tumors by regulating the activity of key genes involved in cell growth. "We found that the DES treatment somehow ’reprogrammed’ how these genes respond to estrogen, making them much more responsive to estrogen than normal," said Walker. "We realized that the DES exposure enabled estrogen to drive the tumor development when combined with a genetic predisposition."

While DES exposure can lead to the development of vaginal and cervical cancers, the fact that most DES-exposed women did not develop the cancers suggests that genetic predisposition is an important part of the equation. "In most cases, we already have tests that can determine if a woman has a genetic predisposition for cancer," said Walker.

This is not the first study to suggest that cancer risk is influenced by both genetic and environmental factors. A 2003 study of Jewish women born with a defect in BRCA1, the gene that is linked to inherited forms of breast and ovarian cancer, showed that those women born before 1940 had a much lower risk of developing breast cancer than women born after 1940. The researchers believe this discrepancy is due to differences in diet, exercise, hormonal factors and chemical exposures.

Walker believes more research needs to be done to test this concept in people. "NIEHS is partnering with the National Academy of Sciences to fund additional research on early-life exposures and cancer risk in human populations," she said.

John Peterson | EurekAlert!
Further information:
http://www.niehs.nih.gov

More articles from Life Sciences:

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

nachricht Pollen taxi for bacteria
18.07.2018 | Technische Universität München

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

NYSCF researchers develop novel bioengineering technique for personalized bone grafts

18.07.2018 | Life Sciences

Machine-learning predicted a superhard and high-energy-density tungsten nitride

18.07.2018 | Materials Sciences

Why might reading make myopic?

18.07.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>