Molecular Toxicology 101 for the lay-person.

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.

What is the main focus of the Vanden Heuvel lab?

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.

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 species and predict whether cancer will develop after exposure to PPs.

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