Peter J. Harvison PhD

Peter J. Harvison PhD

The Leonard & Madlyn Abramson Chair in Pharmacology
Professor of Pharmacology and Toxicology
Research Professor of Medicinal Chemistry

Education

BS (Carnegie-Mellon University)

PhD (SUNY Buffalo)

Research Interests

  • Drug metabolism
  • HPLC method development
  • Structure activity/toxicity relationships

The effects of metabolism on the biological activity of chemicals (including drugs) to which humans and other mammals may be exposed. Research has focused on compounds that contain cyclic imide rings

Synopsis

My research interests are 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, my 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, we have 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. We are 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. We use 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 us understand why NDPS, DCPT, and other chemicals can produce organ damage in animals and humans. 

Selected Scholarly Activity

C.M. Crincoli, N.N. Patel, R. Tchao and P.J. Harvison, “Role of biotransformation in 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT)-induced hepatotoxicity in Fischer 344 rats,” Toxicology 250, 100-108 (2008).
N.N. Patel, C.M. Crincoli, E.L. Kennedy, D.M. Frederick, R. Tchao and P.J. Harvison, Effect of gender, dose and time on 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT)-induced hepatotoxicity in Fischer 344 rats,” Xenobiotica 38, 435-449 (2008).
D. Cui, G.O. Rankin and P.J. Harvison, "Metabolism of the nephrotoxicant N-(3,5-Dichlorophenyl)succinimide in rats: Evidence for bioactivation through alcohol-O-glucuronidation and O-sulfation,” Chem. Res. Toxicol. 18, 991-1103 (2005).
D. Cui, G. O. Rankin, and P. J. Harvison, “Transamination in the metabolism of the nephrotoxicant N-(3,5-dichlorophenyl) succinimide in rats,” Drug Metab. Dispos. 33, 1765-1770 (2005)
E. L. Kennedy, R. Tchao, and P. J. Harvison, “Nephrotoxic and hepatotoxic potential of imidazolidinedione-, oxazolidinedione-, and thiazolidinedione-containing analogues of N-(3,5-dichlorophenyl) succinimide (NDPS) in Fischer 344 rats,” Toxicology 186, 79-91 (2003).
C. M. Henesey and P. J. Harvison, “Renal damage, metabolism and covalent binding following administration of the nephrotoxicant N-(3,5-dichlorophenyl) succinimide(NDPS) to male Fischer 344 rats,” Toxicology 187, (2002).
D. Cui and P. J. Harvison, "Determination of the site of glucuronidation in an N-(3,5-dichlorophenyl) succinimide metabolite by electrospray tandem mass spectrometry following derivatization to picolinyl esters,” Rapid Commun. Mass Spectrom 14,1985 (2000).

Contact Information

Office location: Pharmacology/Toxicology Center Room 237
Mailing address: Box 118
University of Sciences
600 South 43rd Street
Philadelphia, PA 19104-4495
Office Phone: 215.596.8979
Email:

p [dot] harvis [at] usciences [dot] edu