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 cancer.
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 inhaled.
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.
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