MERIT Award Recipient: F. Peter Guengerich, Ph.D.
Metabolism of Carcinogenesis and Drug by Human P450
The research involves the transformation of chemicals in the body, particularly those that can cause cancer. Most of these chemicals, called carcinogens, are not inherently dangerous themselves but are converted in the body to more dangerous forms that damage DNA and cause cancer. The major systems involved in this process in the body are cytochrome P450 (P450) enzymes. Efforts in this laboratory have led to the identification of which of the 57 P450 systems in humans are most involved in carcinogen metabolism. The functions of one-fourth of the human P450 enzymes are still unknown, and further work will focus on what these enzymes do, e.g. where they are located, how much they vary among people, and what chemicals they process. The P450 enzymes are also the main systems that process drugs, including most drugs used for cancer therapy. The general hypothesis is that differences in the P450 enzymes among people are important in influencing individual variations in cancer susceptibility and response to treatment. Other basic research in this project is oriented to understanding the structures and functions of the human P450 enzymes and why individual P450 enzymes process different chemicals.