Peter Harvison, PhD., has research interests primarily concerned with the effects of metabolism on the biological activity of chemicals (including drugs) to which humans and other mammals may be exposed. Although metabolism usually results in the formation of nontoxic substances, the opposite can also occur. For example, some chemicals are actually converted into highly toxic metabolites that can damage tissues or cause cancer. In particular, Dr. Harvison's research has focused on compounds that contain cyclic imide rings. One such compound, known as N-(3,5-dichlorophenyl) succinimide (NDPS), was originally developed as an agricultural fungicide. Although NDPS is an effective antifungal agent, it is converted into metabolites that can produce severe kidney damage in laboratory rats. In fact, NDPS has never been used commercially in the U.S. due to concerns about its potential toxicity in humans. However, humans are exposed to compounds that are structurally related to NDPS. More recently, Harvison has been evaluating an analogue of NDPS, known as 3-(3,5-dichlorophenyl)-2, 4-thiazolidinedione (DCPT). This compound differs from NDPS only in that it contains a sulfur atom in the cyclic imide ring. However, this minor structural change is sufficient to switch the target organ for toxicity from the kidneys to the liver in rats. Harvison is interested in determining why DCPT produces liver damage since it has a structural feature in common with drugs that are used to treat type II diabetes in humans. He uses a variety of techniques, including organic synthesis, high performance liquid chromatography (HPLC), and mass spectrometry, to investigate these compounds. The results of these studies may help people understand why NDPS, DCPT, and other chemicals can produce organ damage in animals and humans.
