The following news release is being issued today by the U.S. Department
of Energy's Brookhaven National Laboratory. An electronic version of
this news release is available in our online newsroom at:
http://www.bnl.gov/bnlweb/pubaf/pr/P...asp?prID=05-84 .


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NEWS RELEASE
Number: 05-84
EMBARGOED for release on Tuesday, September 6, 2005

Smoking Damages Key Regulatory Enzyme in the Lung


UPTON, NY - Smoking appears to reduce a key enzyme in the lungs,
possibly contributing to some of smoking's deleterious health effects,
according to a study published in the September issue of the Journal of
Nuclear Medicine by scientists at the U.S. Department of Energy's
Brookhaven National Laboratory and their collaborators. The study,
which used a radiotracer to track the enzyme, also shows that smokers
had a lower concentration of the tracer in the bloodstream than
nonsmokers did, leading to speculation that smokers and nonsmokers may
respond differently to a variety of substances administered by
inhalation or intravenously, including therapeutic, anesthetic, and
addictive drugs.

"The effects of smoking on human health are enormous; yet, little is
known about the pharmacologic effects of smoking on the human body
apart from the effects of nicotine," noted lead author Joanna Fowler,
director of the Center for Translational Neuroimaging at Brookhaven.

Fowler and collaborators from Brookhaven, the National Institute on
Drug Abuse (NIDA), and Stony Brook University used positron emission
tomography (PET) scanning and a tracer chemical that binds to a
specific form of the enzyme monoamine oxidase (MAO A) to track MAO A
levels in nine smokers and nine nonsmokers. With whole-body PET
imaging, researchers could measure the concentration and movement of
the radiotracer and MAO A, a subtype of the enzyme crucial to mood
regulation and one that breaks down chemical compounds that regulate
blood pressure.

The scans revealed that MAO A was fairly well "intact" in all of the
peripheral organs except in smokers' lungs, said Fowler. Smokers had
MAO A levels that were 50 percent lower than in nonsmokers, she said,
noting that a prior study had also shown a significant reduction of MAO
A in smokers' brains.

MAO A breaks down many compounds that affect blood pressure, and the
lung is a major metabolic organ in degrading some of these compounds,
Fowler said. So reduced levels of MAO A in smokers' lungs may be a
significant factor contributing to some of the physiological effects of
smoking, including changes in blood pressure and pulmonary function.

Smokers' lungs also held onto the tracer chemical much longer than
nonsmokers, and the delivery of tracer into the arterial blood supply
was much lower for smokers, particularly for the first few minutes
after being injected, Fowler added. This finding could imply that
smokers and nonsmokers respond differently to other substances that
enter the body via the bloodstream, including therapeutic drugs,
anesthetics, abused substances, environmental agents - even nicotine.

Fowler and her colleagues have been studying MAO for more than 30
years. Previous research by their group revealed that smokers have
reductions in another subtype of the enzyme, MAO B, in the brain and in
a variety of the body's peripheral organs when compared to nonsmokers
(see: http://www.bnl.gov/bnlweb/pubaf/pr/2003/bnlpr090803.htm).

"These studies showing for the first time that smokers have reduced
levels of MAO in their brains and in certain peripheral organs shed
mechanistic light on some of the more puzzling aspects of smoking,
including a reduced rate of Parkinson's disease in smokers and a high
rate of smoking among people with depression and those addicted to
other substances," Fowler said. The role played by MAO in other
conditions associated with smoking may also be significant and deserves
further investigation, considering the differences observed in the
enzyme level between smokers and nonsmokers, she said.

Cigarette smoking accounts for 440,000 deaths each year in the United
States, or nearly one of every five deaths, according to the Centers
for Disease Control and Prevention. Smoking kills more Americans than
AIDS, illegal drugs, alcohol, car accidents, suicides and murders
combined and increases one's chances of developing lung, bladder,
esophageal and throat cancers; chronic lung diseases; and coronary
heart and cardiovascular diseases. This research was funded by the
Office of Biological and Environmental Research within the U.S.
Department of Energy's Office of Science, and by NIDA, a division of
the National Institutes of Health. PET imaging is a direct outgrowth of
the Department of Energy's long-standing investment in basic physics
research.

"It's important that the public know about the benefits derived from
the DOE's long-term investments in basic science - especially in
radioisotope and radiotracer chemistry and imaging physics - which have
played such an important role in introducing new nuclear medicine
procedures into the practice of health care," Fowler said.

One of ten national laboratories overseen and primarily funded by the
Office of Science of the U.S. Department of Energy (DOE), Brookhaven
National Laboratory conducts research in the physical, biomedical, and
environmental sciences, as well as in energy technologies and national
security. Brookhaven Lab also builds and operates major scientific
facilities available to university, industry and government
researchers. Brookhaven is operated and managed for DOE's Office of
Science by Brookhaven Science Associates, a limited-liability company
founded by Stony Brook University, the largest academic user of
Laboratory facilities, and Battelle, a nonprofit, applied science and
technology organization.
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Sheldon