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Education: A. B. Whitman College
M. S. University of Idaho
Ph.D., Cornell University
Post-doctoral Harvard Medical
School, Massachusetts General Hospital and
University of Texas Medical Branch
Research:
Sensitivity to genotoxic effects of butadiene
What is butadiene and why is it
important? Butadiene
is a chemical that is used in large volumes to manufacture synthetic rubber and
other polymers. It is also a combustion product found in automobile emissions
and environmental tobacco smoke. Urban air typically contains 0.1 to 10 parts
per billion of butadiene. It is a potent carcinogen in mice and is a probable
carcinogen in humans. Occupational exposure to butadiene has been associated
with leukemia.
How do we study butadiene? We are investigating the ability of
butadiene to damage the genetic apparatus, a predisposing process that can lead
to cancer, in two ways. First we are conducting studies directly in human
populations by using tests to measure exposure to butadiene, tests that measure
an effect of butadiene, and a third class of tests that determine human genetic
traits that may make people more or less sensitive to the toxic effects of
butadiene. These tests are called biomarkers and the approach we
use is often referred to as molecular epidemiology. We have
conducted studies on groups of workers in chemical plants where butadiene is
made or used to make polymers. In these studies we have selected workers from
areas where butadiene levels are relatively high or low. We have measured the
concentration of butadiene in the air the workers breath, and determined how
much they actually absorbed by measuring the concentration of a metabolite of
butadiene in the urine. We also measured the effects of exposure by determining
the frequency of mutations at a "reporter gene" called HPRT in
white blood cells. In several studies we found that the frequency of HPRT
mutant lymphocytes was higher in workers with the greatest exposure to
butadiene. We have also investigated the inherited traits of some workers in
genes that control the way butadiene is broken down and eliminated after
entering the body. We found that individuals who have a genetic trait that
reduces the activity of an enzyme that breaks down the toxic metabolites of
butadiene have higher HPRT mutant frequencies if they are exposed to
butadiene than workers with a form of the gene that produces normal levels of
enzyme activity. The enzyme is called microsomal epoxide hydrolase.
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You can read more about our research
in the following recent scientific publications.
Abdel-Rahman, S.Z., Ammenheuser,
M.M. and Ward, J.B., Jr. Human sensitivity to 1,3-butadiene:
role of microsomal epoxide hydrolase polymorphisms. Carcinogenesis, vol. 22,
no. 3, pp. 415-423, 2001.
Ward, J.B., Jr.,
Abdel-Rahman, S.Z., Henderson, R.F., Stock, T.H., Morandi, M., Rosenblatt, J.I.
and Ammenheuser, M.M. Assessment of butadiene exposure in synthetic rubber
manufacturing workers in Texas using frequencies of hprt mutant lymphocytes as
a biomarker. Chemico-Biol Interactions, 135-136: 465-483, 2001.
Ammenheuser, M.M. Bechtold,
W.E., Abdel-Rahman, S.Z., Rosenblatt, J.I., Hastings-Smith, D.A. and Ward,
J.B.Jr., Assessment of 1,3-butadiene exposure
in polymer production workers using hprt mutation in lymphocytes as a
biomarker. Environment. Health Perspect, vol. 109, 12:1249-1255, 2001.
Abdel-Rahman, S. Z., El-Zein,
R. A., Ammenheuser, M. M., Yang, Z, Stock, T. H. Morandi, M., and Ward, J. B.
Jr., Variability in human sensitivity to 1,3-butadiene: Influence of allelic
variations of the microsomal epoxide hydrolase gene. Environ. Molec. Mutagen. 41:140-146, 2003.
Wickliffe, JK, Ammenheuser, MM, Salazar,
JA, Abdel-Rahman, SZ, Hastings-Smith, DA, Postlethwait, EM, Lloyd,
RS, and Ward, JB Jr. A model of sensitivity: 1,3-butadiene increases mutant
frequencies and genomic damage in mice lacking a functional microsomal epoxide
hydrolase gene, Environ. Molec. Mutagen. In press.
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PMCH
