HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Henderson, C. J. Articles by Wolf, C. R. Search for Related Content PubMed PubMed Citation Articles by Henderson, C. J. Articles by Wolf, C. R.

Transgenic Analysis of Human Drug–Metabolizing Enzymes: Preclinical Drug Development and Toxicology

Cancer Research UK, Molecular Pharmacology Unit Biomedical Research Centre, Ninewells Hospital & Medical School Dundee, DD1 9SY, United Kingdom

The lack of multiple cytochrome P450 activities in early development can be studied in a transgenic mouse. Most striking here is the effect on blood vessel formation in the yolk sac of transgenic mice that lack cytochrome P450 reductase (right), relative to wild type (left) 23).

The cytochromes P450 (CYPs) are drug-metabolizing enzymes (DMEs), and constitute a large family of monooxygenases, arising from multiple genes, capable of catalyzing an extraordinary range of biochemical reactions, from the synthesis of cholesterol, bile acids, and steroid hormones to the metabolism of drugs, prodrugs, and xenobiotics. The CYPs, along with other DMEs, remain the subject of intense scientific research not only to ascertain their functions in vivo, but also to better understand how the expression of these enzymes is regulated. Transgenic technologies are providing important animal models for studying how DMEs—including the particularities of human DMEs—provide an adaptive response to cellular stress, establishing relationships between polymorphisms and disease susceptibility, and investigating how CYPs and other DMEs determine the pharmacological action of therapeutic drugs¹.

This article has been cited by other articles:

				L. A. McLaughlin, L. J. Dickmann, C. R. Wolf, and C. J. Henderson Functional Expression and Comparative Characterization of Nine Murine Cytochromes P450 by Fluorescent Inhibition Screening Drug Metab. Dispos., July 1, 2008; 36(7): 1322 - 1331. [Abstract] [Full Text] [PDF]

				V. M. Arlt, M. Stiborova, C. J. Henderson, M. Thiemann, E. Frei, D. Aimova, R. Singh, G. Gamboa da Costa, O. J. Schmitz, P. B. Farmer, et al. Metabolic activation of benzo[a]pyrene in vitro by hepatic cytochrome P450 contrasts with detoxification in vivo: experiments with hepatic cytochrome P450 reductase null mice Carcinogenesis, March 1, 2008; 29(3): 656 - 665. [Abstract] [Full Text] [PDF]

				M. A. Felmlee, H.-K. Lon, F. J. Gonzalez, and A.-M. Yu Cytochrome P450 Expression and Regulation in CYP3A4/CYP2D6 Double Transgenic Humanized Mice Drug Metab. Dispos., February 1, 2008; 36(2): 435 - 441. [Abstract] [Full Text] [PDF]

				G. J. Pass, D. Carrie, M. Boylan, S. Lorimore, E. Wright, B. Houston, C. J. Henderson, and C. R. Wolf Role of Hepatic Cytochrome P450s in the Pharmacokinetics and Toxicity of Cyclophosphamide: Studies with the Hepatic Cytochrome P450 Reductase Null Mouse Cancer Res., May 15, 2005; 65(10): 4211 - 4217. [Abstract] [Full Text] [PDF]