February 11, 2014
Researchers at the Maxine Dunitz Neurosurgical Institute and Department
of Neurosurgery at Cedars-Sinai will conduct a study to determine if
several potentially toxic compounds that exist in polluted air are
capable of entering the brain from the bloodstream and causing brain
The research, funded by a $1 million grant from the Brain & Lung
Tumor and Air Pollution Foundation for the South Coast Air Quality
Management District, will be done in laboratory mice.
The National Toxicology Program, an interagency program of the U.S.
Department of Health and Human Services and the Institute of
Environmental Health Services, part of the National Institutes of
Health, has identified 13 chemicals that have caused brain tumors. The
Cedars-Sinai study will focus on three – naphthalene, butadiene and
isoprene – that often are associated with polluted air.
Naphthalene, used in the plastics industry and a component of
mothballs and other products, may be released into the air when coal and
oil are burned. Butadiene, used in rubber manufacturing and found in
vehicle exhaust, exists in low levels in the air of urban and suburban
areas. Isoprene, a natural compound produced by certain trees and
shrubs, is used in manufacturing synthetic rubber and adhesives. Alone,
it usually is not considered an air pollutant, but when it mixes with
high levels of nitric oxide – which often occurs in industrial areas –
the combination produces "ground-level" ozone, which can be harmful when
Cedars-Sinai researchers and others have used high-tech systems to
detect genes and proteins involved in the development of brain cancers.
They have studied molecular changes and interactions considered "brain
tumor pathways" that lead from defective gene activity to cancer
generation in the brain. The researchers also have identified certain
genes that appear to support cancer stem cells. Like normal stem cells,
cancer stem cells have the ability to self-renew and generate new cells,
but instead of producing healthy cells, they create cancer cells.
The air pollution study is intended to determine whether up to 12
months of ongoing exposure to air pollution causes molecular changes in
the brain that are consistent with the development of brain tumor
pathways; if toxins associated with air pollution can cross the brain's
natural defense mechanism – the blood-brain barrier – and enter the
brains of animals; and whether this exposure activates genes and
proteins that support brain cancer stem cells.
"Most studies looking at central nervous system cancers have focused
on occupational hazards and have found that many manufacturing, farming,
chemical and other industries are associated with increased risk. In
this study, we will learn about particular components of air pollution
and how they may be involved with the abnormal expression of genes and
proteins that activate cancer stem cells. This may increase our
understanding of air pollution as a potential risk factor for the
generation of brain cancer," said Keith Black, MD, chair and professor
of the Department of Neurosurgery, director of the Maxine Dunitz
Neurosurgical Institute, director of the Johnnie L. Cochran, Jr. Brain
Tumor Center and the Ruth and Lawrence Harvey Chair in Neuroscience.
Black is principal investigator of this study. He and other
Cedars-Sinai researchers have conducted earlier studies on air pollution
and molecular brain changes that could lead to cancer development –
primarily on the potential effects of diesel fuel exhaust – for the
South Coast Air Quality Management District.
In the new study, researchers will examine tissue exposed to
pollutants at three months, six months and 12 months to determine if
there is a change with longer exposure compared to shorter.
Provided by Cedars-Sinai Medical Center