MUTAGENIC EFFECTS OF AIRBORNE TOXICANTS IN LUNGS

  • Zarbl, Helmut (PI)
  • Tannenbaum, Steven (PI)
  • Sarofim, Adel (PI)
  • Busby, William (PI)
  • Utell, Mark (PI)
  • Thilly, William (PI)
  • Lafleur, Arthur (PI)
  • Willey, James (PI)
  • Howard, Jack (PI)

Project Details

Description

This Program seeks to discover if the mutations, especially oncomutations,
in the bronchial cells of human lungs from nonsmokers are principally
caused by exposure to air-borne chemicals in urban outdoor and
environments. To achieve this goal, we propose to study the expression of lung cell
xenometabolic genes associated with mutagen activation in bronchial brush
biopsies of males and females, smokers and nonsmokers, Afro- and Euro
Americans. Because we measure the amount of protein and DNA adducts and
mutations in each of these biopsies we expect to define xenometabolic
patterns associated with high risk of lung genetic damage. These patterns
we will engineer into human diploid cells for use in determining the
chemicals principally responsible for the mutagenicity of environmental
air samples from four American cities; Washington D.C., Los Angeles, CA,
Rochester NY, and Woburn, MA. These research goals require a carefully
managed cross-disciplinary team of combustion and environmental engineers,
analytical chemistry, lung physiologists and genetic toxicologists. We further propose to measure certain oncomutations associated with human
lung cancer (K-ras, P53 genes) as function of anatomical position in the
bronchial tree and to observe the amount chemical adducts and
mitochondrial mutations in these same dissection samples. The results of
this study will determine if oncomutations arise as developmental
jackpots, if mutations are associated with bronchiolar bifurcations having
high air-borne chemical deposition and if the kinds of mitochondrial
mutations observed are those induced in human cell studies in which air-
borne chemicals are known to be the responsible mutagens. The program is a combination of original analytical and synthetic
approaches in the fields of analytical chemistry and analytical genetics.
The strengths of three research universities are combined: lung
physiology at the University of Rochester Medical School; area-grid air
sampling and source attribution at the California Institute of Technology
combustion engineering, complex mixture analysis and genetic toxicology at
M.I.T.
StatusFinished
Effective start/end date8/1/947/31/03

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Environmental Science(all)
  • Medicine(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.