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(or Molecular Toxicology 101)
Toxicology, the science of poisons, identifies and quantifies potentially
noxious agents in our environment. The essence of the science of
toxicology is defining the fine line distinguishing between tolerable
and unacceptable risks to humans and other organisms in the manufacturing,
handling, use and disposal of chemical agents. Mechanism-oriented
investigative toxicology encompasses the disciplines of anatomy,
physiology, biochemistry, chemistry, immunology, pharmacology, cell
and molecular biology as well as pathology and laboratory medicine.
The toxicologist must be well versed in not only human and veterinary
medicine, but also in the various aspects of agricultural and nutritional
sciences. Only through rigorous basic scientific research can responsible
regulation of potentially hazardous compounds be achieved.
As stated above, toxicology is the study of poisons, and it tends
to focus on chemical agents. My laboratory examines a group of chemicals
known as peroxisome proliferators (PPs). These chemicals are very
important in toxicology for the following reasons:
- PPs are widely used drugs. They are used to treat high fat levels
and diabetes. Drugs that are considered to be PPs are clofibric
acid, gemfibrzil and troglitazone.PPs are very effective drugs for
treating hypolipidemia and adult onset diabetes
- A wide variety of industrial chemicals and environmental pollutants
are PPs. For example, chemicals used in making plastics such
as dibutyl phthalate and chemcials used as fire retardants such as
perfluorooctanoic acid are PPs. Also, the herbicide 2,4-D that is
commonly used in lawn-care products is a PPs.
- A group of natural chemicals, in particlar fatty acids, have activity
similar to the man-made PPs.
- When fed to laboratory animals, PPs lead to cancer of the liver,
pancreas and testes. The mechanism by which PPs cause cancer
in rats and mice is unknown.
As stated above, humans are exposed to PPs frequently both in the
clinic and the environment. Risk of developing cancer is the primary
concern of this exposure. My laboratory is interested in HOW PPs
cause cancer in a susceptible species. With this information, we
can then assess whether humans are at risk in a logical and scientifically-based
manner. For example, from studies performed with rats and mice, we
know a protein called PPAR is involved in the carcinogenicity of
PPs. Subsequent studies showed humans express this protein and that
it molecular regulation is quite similar to the rodent counterparts.
There are subtle differences in how human PPAR and mouse PPAR are
controlled, which we can now examined in more detail. The bottom-line
remains, if we know how PPs cause cancer in one species, we can dissect
this mechanism in another sepcies and predict whether cancer will
develop after exposure to PPs.
I hope that this primer helped. The pages that follow
are laden with technical jargon that may be quite difficult to understand.
If you have questions, please feel free to contact me at jpv2 at psu.edu.
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