Vol. 305, Issue 2, 403-409, May 2003

Genetics and Susceptibility to Toxic Chemicals: Do You (or Should You) Know Your Genetic Profile?

Lawrence H. Lash, Ronald N. Hines, Frank J. Gonzalez, Timothy R. Zacharewski and Mark A. Rothstein

Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan (L.H.L.); Birth Defects Research Center, Departments of Pediatrics and Pharmacology/Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin (R.N.H.); Laboratory of Metabolism, National Cancer Institute, Bethesda, Maryland (F.J.G.); Department of Biochemistry and Molecular Biology, National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan (T.R.Z.); and Institute for Bioethics, Health Policy and Law, University of Louisville School of Medicine, Louisville, Kentucky (M.A.R.)

This review is based on a symposium/roundtable session, sponsored by the Division of Toxicology of the American Society for Pharmacology and Experimental Therapeutics, that was held at the 2002 Experimental Biology meeting in New Orleans, LA. The focus is on the role of pharmacogenomics in determining individual susceptibility to chemically induced toxicity. An individual's risk of disease from exposure to toxic chemicals is determined by a complex interplay between genetics, physiology, and concurrent or prior exposures to drugs and other chemicals. The first section of the review defines the basics of pharmacogenetics and pharmacogenomics and assesses the current state of the science. Selected applications to specific enzyme systems are summarized by way of example. New, state-of-the-art approaches to studying genetic determinants of susceptibility, including analytical methods and transgenic technology, are then discussed. Finally, ethical and legal concerns with the application of this knowledge and methodology to human health will be discussed.