Early exposure to synthetic estrogen in the womb..

J · medicine forum addict Joined: 07 May 2005 Posts: 93

http://www.forbes.com/lifestyle/health/feeds/hscout/2005/05/31/hscout525949.html

Early Environmental Exposure May Set Stage for Cancer
By Steven Reinberg
HealthDay Reporter

TUESDAY, May 31 (HealthDay News) -- Researchers think they have discovered
why some people who are genetically prone to cancer develop the disease,
and some do not.

In experiments with rats, scientists found that exposure to synthetic
estrogen in the womb can permanently "reprogram" cells in a way that
determines whether cancer will develop in adulthood. Their report appears
in this week's issue of the Proceedings of the National Academy of
Sciences.

"We found that very early life exposures seem to have a very profound
effect on determining which individual will get cancer as an adult," said
lead researcher Cheryl Walker, a professor in the Department of
Carcinogenesis at the University of Texas M.D. Anderson Cancer Center in
Houston.

"We were interested in those people who might be genetically predisposed
to cancer," Walker said. "But not all genetically susceptible people
actually develop cancer. In fact, the rate of cancer in those that have
these genetic defects can be very high or very low, and we don't know why
that is."

That means there are most likely environmental influences that set these
genes in motion, Walker explained. "Our work found that environmental
exposure that occurs early in life, a long time before the cancer
develops, might be determining which of these genetically susceptible
individuals will develop cancer as an adult," she said.

In their experiments, Walker and her colleagues used an animal model that
had a similar genetic defect that is found in some people susceptible to
tumors. In this case it was uterine leiomyoma, the same kind of benign
fibroid tumors that many women have.

In rats engineered to be susceptible to benign uterine tumors, Walker's
team treated some with diethylstilbestrol (DES), a banned anti-miscarriage
drug.

Usually, about 65 percent of rats with this genetic defect develop the
tumors as adults. In the experiment, some rats were exposed to DES three
to five days after birth.

By the time the DES-exposed rats reached adulthood, almost all had
developed tumors. Moreover, there were more and larger tumors in the
DES-exposed rats, compared with unexposed rats that had the genetic
defect. In contrast, rats that did not have the genetic defect but were
exposed to DES did not develop tumors.

"This environmental exposure, during a critical developmental time, had a
profound effect on the uterus," Walker said. "In fact, what it did was it
reprogrammed the way the normal uterus responds to the female hormone
estrogen. This is a new type of gene/environment interaction."

Walker believes this interaction is the mechanism that is also involved in
human cancer. "If we want to understand how the environment contributes to
cancer, we can't just look at adult exposures," she said. "We are going to
have to look at early life exposures."

Walker also cautioned that looking at environmental causes of cancer that
result from gene mutations is not the whole story. "In this study, we have
not induced mutations; we have reprogrammed the tissue in such a way that
it is responding differently. It is that reprogrammed tissue, combined
with the genetic alteration, that drives tumor development."

One expert finds the study interesting, but not entirely convincing.

"We knew from earlier studies that early exposure to DES is linked to
cancers of the female genital tract, so this is not completely
surprising," said Dr. Archibald S. Perkins, an associate professor of
pathology and molecular, cell and developmental biology at Yale
University.

What is new here is that the impact of early hormonal exposure can depend
on the presence of genetically inherited traits, indicating that certain
individuals will be affected, while others will not, Perkins said. "This
study also starts to uncover the mechanism by which these brief exposures
lead to later effects," he noted.

However, what the implication might be for people isn't clear. "Whether
this study has implications for exposure to environmental agents, such as
pesticides, is not clear since such environmental agents are likely
present at very low levels, while the DES levels the rats were exposed to
were quite high," Perkins said. "That would be the obvious concern,
however, that environmental agents could cause, in the susceptible
individual, a change in some target organ that would only become evident
much later."

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