Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (123)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Crespi, C. L.
Right arrow Articles by Langenbach, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Crespi, C. L.
Right arrow Articles by Langenbach, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1990 Oxford University Press

other

Human cytochrome P450IIA3: cDNA sequence role of the enzyme in the metabolic of promutagens comparison to nitrosamine activation by human cytochrome P450IIE1

Charles L. Crespi, Bruce W. Penman, Julian A.E. Leakey 1, Michael P. Arlotto 1 5, Avishay Stark 2, Andrew Parkinson 3, Thomas Turner, Dorothy T. Steimel, Ken Rudo 4, Robin L. Davies 6 and Robert Langenbach 4

Gentest Corporation 6 Henshaw Street, Woburn, MA 01801
1National Center of Toxicological Research Jefferson, AR 72079, USA
2Tel Aviv University Ramat-Aviv 69978, Tel Aviv, Israel
3Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center Kansas City, KS 66103
4National Institute of Environmental Health Science PO Box 12233, Research Triangle Park, NC 27709, USA

We report that, in a human cell line, human cytochrome P450IIA3 is capable of metabolizing aflatoxin B1 benzo[a]pyrene, N-nitrosodimethylamine (NDMA) and N-nitroso diethylamine (NDEA) to cytotoxic and mutagenic species. Cytochrome P450IIA3-mediated activation of NDMA and NDEA was compared with human cytochrome P450IIE1- mediated activation in the same cell system. P450IIE1 was more effective at activating NDMA than P450IIA3, while P450IIA3 was more effective at activating NDEA than P450IIE1. Whole cells and microsomal fractions obtained from control cells and from cells expressing the P450IIA3 cDNA were characterized for expression of P450IIA3. Microsomal coumarin 7-hydroxylase activity was some 40 times greater in the transfected cells than in the control cells and was catalyzed by a protein that was immunochemically related to the rat liver cytochrome P450IIA gene family. Immunoblot analysis demonstrated that this protein was readily detectable in transfected cells but barely detectable in control cells. We also report the DNA and deduced amino acid sequence of the P450IIA3 cDNA isolate used in this study. Our isolate encodes a protein 489 amino acids that is five amino acids shorter at the N terminus but otherwise identical to a previously reported human P450IIA3 cDNA sequence.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Exp ToxicolHome page
B Sinues, A Fanlo, E Mayayo, C Carcas, J Vicente, I Arenaz, and A Cebollada
CYP2A6 activity in a healthy Spanish population: effect of age, sex, smoking, and oral contraceptives
Human and Experimental Toxicology, May 1, 2008; 27(5): 367 - 372.
[Abstract] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
S. Nowell, C. Sweeney, G. Hammons, F. F. Kadlubar, and N. P. Lang
CYP2A6 Activity Determined by Caffeine Phenotyping: Association with Colorectal Cancer Risk
Cancer Epidemiol. Biomarkers Prev., April 1, 2002; 11(4): 377 - 383.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
R. F. Tyndale and E. M. Sellers
Variable CYP2A6-Mediated Nicotine Metabolism Alters Smoking Behavior and Risk
Drug Metab. Dispos., April 1, 2001; 29(4): 548 - 552.
[Abstract] [Full Text]

Home page
 Mol. Pharmacol.Home page
Y. Rao, E. Hoffmann, M. Zia, L. Bodin, M. Zeman, E. M. Sellers, and R. F. Tyndale
Duplications and Defects in the CYP2A6 Gene: Identification, Genotyping, and In Vivo Effects on Smoking
Mol. Pharmacol., October 1, 2000; 58(4): 747 - 755.
[Abstract] [Full Text]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
C. Chen, L. S. Cook, X.-Y. Li, S. Hallagan, M. M. Madeleine, J. R. Daling, and N. S. Weiss
CYP2D6 Genotype and the Incidence of Anal and Vulvar Cancer1
Cancer Epidemiol. Biomarkers Prev., April 1, 1999; 8(4): 317 - 321.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K.-I. Nunoya, T. Yokoi, K. Kimura, T. Kainuma, K. Satoh, M. Kinoshita, and T. Kamataki
A New CYP2A6 Gene Deletion Responsible for the In Vivo Polymorphic Metabolism of (+)-cis-3,5-Dimethyl-2-(3-pyridyl)thiazolidin-4-one Hydrochloride in Humans
J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 437 - 442.
[Abstract] [Full Text]

Home page
 CarcinogenesisHome page
M. Lechevrel, A. G. Casson, C. R. Wolf, L. J. Hardie, M. B. Flinterman, R. Montesano, and C. P. Wild
Characterization of cytochrome P450 expression in human oesophageal mucosa
Carcinogenesis, February 1, 1999; 20(2): 243 - 248.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
G. M. Kirby, G. Batist, L. Alpert, E. Lamoureux, R. G. Cameron, and M. A. Alaoui-Jamali
Overexpression of Cytochrome P-450 Isoforms Involved in Aflatoxin B1 Bioactivation in Human Liver with Cirrhosis and Hepatitis
Toxicol Pathol, July 1, 1996; 24(4): 458 - 467.
[Abstract] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.