title: Role of Cytochrome P450 Monooxygenase in Carcinogen and Chemotherapeutic Drug Metabolism.
abstract: The purpose of this chapter is to provide insight into which human cytochromes P450 (CYPs) may be involved in metabolism of chemical carcinogens and anticancer drugs. A historical overview of this field and the development of literature using relevant animal models and expressed human CYPs have provided information about which specific CYPs may be involved in carcinogen metabolism. Definition of the biochemical properties of CYP activity came from several groups who studied the reaction stoichiometry of butter yellow and benzo[α]pyrene, including their role in induction of these enzyme systems. This chapter will list as much as is known about the human CYPs involved in carcinogen and anticancer drug metabolism, as well as summarize studies with rodent CYPs. A review of three major classes of anticancer drugs and their metabolism in humans is covered for cyclophosphamide, procarbazine, and anthracycline antibiotics, cancer chemotherapeutic compounds extensively metabolized by CYPs. The emerging information about human CYP gene polymorphisms as well as other enzymes involved in foreign compound metabolism provides considerable information about how these genetic variants affect carcinogen and anticancer drug metabolism. With information available from individual's genomic sequences, consideration of populations who may be at risk due to environmental exposure to carcinogens or how to optimize their cancer therapy regimens to enhance efficacy of the anticancer drugs appears to be an important field of study to benefit individuals in the future.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
authors.forename: B
authors.initials: B
authors.lastname: Wahlang
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
authors.forename: K Cameron
authors.initials: KC
authors.lastname: Falkner
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky, USA; Department of Biochemistry & Molecular Biology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Matt C
authors.initials: MC
authors.lastname: Cave
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Louisville, Louisville, Kentucky, USA. Electronic address: raprou01@louisville.edu.
authors.forename: Russell A
authors.initials: RA
authors.lastname: Prough
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System
keywords: Anthracycline antibiotics; Carcinogen metabolism; Cyclophosphamide; Cytochrome P450; Gene expression; Gene polymorphism; Nuclear receptors; Procarbazine; Reactive chemical intermediates