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 Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>