DMD

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on April 12, 2007; DOI: 10.1124/dmd.107.015826

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.107.015826v1
35/7/1009    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ma, Q.
Right arrow Articles by Lu, A. Y. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ma, Q.
Right arrow Articles by Lu, A. Y. H.


Received for publication March 19, 2007.
Revised April 10, 2007.
Accepted for publication April 11, 2007.

CYP1A INDUCTION AND HUMAN RISK ASSESSMENT: AN EVOLVING TALE OF IN VITRO AND IN VIVO STUDIES

Qiang Ma 1* Anthony Y. H. Lu 2

1 Receptor Biology Laboratory, TMBB/HELD/CDC/NIOSH 2 Rutgers, The State University of New Jersey

* Address correspondence to: E-mail: qam1{at}cdc.gov

Abstract

CYP1A1 and 1A2 play critical roles in the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons (PAH) and heterocyclic aromatic amines/amides (HAA) to electrophilic reactive intermediates, respectively, leading to toxicity and cancer. CYP1As are highly inducible by PAH and halogenated aromatic hydrocarbons (HAH) via aryl hydrocarbon receptor (AhR)-mediated gene transcription. The impact of CYP1A induction on the carcinogenic and toxic potentials of environmental, occupational, dietary, and therapeutic chemicals has been a central focus of human risk evaluation and has broadly influenced the fields of cancer research, toxicology, pharmacology, and risk assessment over the past half century. From the early discovery of CYP1A induction and its role in protection against chemical carcinogenesis in intact animals, to the establishment of CYP1A enzymes as the principal P450s for bioactivation of PAH and HAA in in vitro assays, to the recent realization of an essential protective role of CYP1A in B[a]p-induced lethality and carcinogenesis with CYP1A knockout mice, the understanding of the interrelation between CYP1A induction and chemical safety has followed a full circle. This unique path of CYP1A research underscores the importance of whole animal and human studies in chemical safety evaluation.


Key words: Ah receptor, CYP induction, CYP1A, cytochrome P450 regulation, drug toxicity, drug-drug interactions, in vitro-in vivo prediction, induction, reactive intermediate, safety evaluation


This article has been cited by other articles:


Home page
 Toxicol SciHome page
S. M. Billiard, J. N. Meyer, D. M. Wassenberg, P. V. Hodson, and R. T. Di Giulio
Nonadditive effects of PAHs on Early Vertebrate Development: mechanisms and implications for risk assessment
Toxicol. Sci., September 1, 2008; 105(1): 5 - 23.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Q. Ma
Ah receptor: xenobiotic response meets inflammation
Blood, August 15, 2008; 112(4): 928 - 929.
[Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics.