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Combination of Two Widely Used Pesticides Linked to Parkinson's Disease - URMC Press Release
      
Press Room HomeNews Home
January 3, 2001
For further information, contact:
Tom Rickey (716) 275-7954
Combination of Two Widely Used Pesticides Linked
to Parkinson's Disease
Scientists have shown that the combination of two widely used
agricultural pesticides-but neither one alone-creates in mice the
exact pattern of brain damage that doctors see in patients with Parkinson's
disease. The research offers the most compelling evidence yet that
everyday environmental factors may play a role in the development
of the disease.
The latest findings of the team led by Deborah Cory-Slechta,
Ph.D., professor of environmental medicine and dean for research at
the University of Rochester School of Medicine and Dentistry, appear
in the Dec. 15 issue of the Journal of Neuroscience. The scientists
caution that more studies are necessary to explain the link, since
it's probable that many factors contribute to a complex disease like
Parkinson's, and they say it's unlikely that the pesticides on their
own actually cause the disease.
Cory-Slechta's team studied the effects of a mixture
of two very common agrichemicals, the herbicide paraquat and the fungicide
maneb. Each is used by farmers on millions of acres in the United
States alone: Maneb is applied widely on such crops as potatoes, tomatoes,
lettuce and corn, and paraquat is used on corn, soybeans, cotton,
fruit, and a variety of other products. In the experiment, mice exposed
to either one had little or no brain damage, but mice exposed to both
share a significant trait with people in the very early stages of
the disease: Though they appear healthy, key brain cells known as
dopamine neurons are dying. The mice exposed to the mixture carried
nearly all of the molecular hallmarks of Parkinson's disease as seen
in humans.
"The environmental reality is that several of these
chemicals are used on the same crops and in the same geographical
locations. You've got to get rid of the weeds. Then the insects. Then
funguses. These are different chemicals that do different things,
but they're often applied in the same fields," says Cory-Slechta,
who was joined in the research by graduate student Mona Thiruchelvam
and faculty members Eric Richfield, Raymond Baggs, and A. William
Tank.
The study is one of the first to examine the effects
of such chemicals in tandem. Cory-Slechta notes that current regulations
and determinations of safety levels are usually based on the effects
of single chemicals. "In the real world, we're exposed to mixtures
of chemicals every day. There are thousands upon thousands of combinations;
I think what we have found is the tip of the iceberg," she says. "There
are a dozen different fungicides related to maneb alone. I don't think
we just happened to pick the right chemicals to see such an effect."
Maneb, paraquat, and many other pesticides are used
in the same agriculture-rich areas of the country, including the Midwest,
California, Florida and the Northeast. The map of their use mirrors
areas of the country where people are more likely to die of Parkinson's
disease.
Several epidemiological studies have hinted at a role
for pesticides in the development of the disease. Studies have found
that farmers, people who live in rural areas, and people who drink
well water are more likely to have the disease than people who don't.
In addition, just last month, scientists at Emory University presented
evidence that rats given a steady dose of the natural pesticide rotenone,
used on home-grown fruits and vegetables, develop Parkinson's-like
symptoms. Cory-Slechta's study, which used much lower levels of chemicals
than the Emory research, is the first to link a combination of more
widely used pesticides to the disease.
"No one has looked at the effects of studying together
some of these compounds that, taken by themselves, have little effect,"
says Cory-Slechta. "This has enormous implications."
Currently scientists have little understanding of what
causes Parkinson's, where a tiny group of dopamine-producing neurons
deep within an area of the brain known as the substantia nigra die.
This cell death leads to a shortage of the neurotransmitter dopamine
and to the tremors, rigidity, and slow movement that mark the disease
as it progresses slowly over a period of years or decades. Parkinson's
affects about 1 million people in North America.
There is a growing consensus among scientists that both
genetic predisposition and environmental agents may play a role in
the disease. Doctors see a similar effect in heart disease, where
a patient might have both a family history and a sedentary lifestyle,
or in cancer, where certain genes may make one prone to develop colon
cancer and a poor diet makes the disease even more likely.
Cory-Slechta thinks it's unlikely that exposures to
such chemicals actually cause Parkinson's on their own, but they may
contribute to the development of the disease. "This is the first time
that truly environmental risk factors for Parkinson's disease have
been identified," she says.
Cory-Slechta heads a research center funded by the National
Institute of Environmental Health Sciences where researchers study
the effects of environmental agents like cigarette smoke, air pollution,
and metals like mercury and lead on human health. She believes scientists
must do more research on the effects of exposure to multiple chemicals.
"It's a huge problem to start thinking about a nearly infinite array
of mixtures of chemicals, instead of the risk that a single chemical
might pose," she says.
She also says more work must be done to see how much
of these chemicals people are actually exposed to. Usually it's not
clear exactly how much of a pesticide remains on crops by the time
they reach the dinner table. Maneb frequently shows up as a slight
residue, she says, while paraquat usually shows up just in trace amounts;
exposures can also occur via other routes. Oftentimes the two are
used at different stages of the growing cycle. "The real issue is
what happens when they hit humans in the food chain. If they're both
present, then you are exposed to the combination."
In the Journal of Neuroscience paper, and in
an earlier paper in Brain Research, the scientists showed how
mice injected with both maneb and paraquat differed from normal mice
in many ways. Most obviously, the mice moved around much less; immediately
after the last of 12 injections over six weeks, the mice ran around
their cages just one-tenth as much as their normal counterparts. More
importantly, the mice that received both chemicals showed brain damage
in exactly the same way as humans with Parkinson's:
The amount of a key molecular marker, tyrosine hydroxylase, that
is one measure of the health of the dopamine system was lower by
about 15 percent in the mice, in the exact same areas of the brain
that are damaged by the disease. Other closely related areas of
the brain were spared, as in humans.
The mice had nearly four times as many "reactive astrocytes,"
structures which indicate brain damage, compared to the control
mice, in areas affected by Parkinson's disease.
The mice had about 15 percent fewer dopamine neurons and ultimately
produced about 15 percent less dopamine than normal mice.
The team is currently pursuing several new avenues of research,
with funding from NIEHS. For instance, preliminary findings indicate
that the Parkinson's-like effects on mice may be permanent, and that
older mice may be more sensitive to the combination than younger mice.
The team is also studying the effects of exposure to the mixture early
in life, and they've shown that mice with the same genetic abnormality
that causes some people to develop Parkinson's are specially vulnerable
to the mixture.
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