DMD Noab BioDiscoveries - Shaping Drug Discovery

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


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Vakharia, D. D.
Right arrow Articles by Kaminsky, L. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vakharia, D. D.
Right arrow Articles by Kaminsky, L. S.

Vol. 29, Issue 7, 999-1006, July 2001

SHORT COMMUNICATION
Polycyclic Aromatic Hydrocarbon/Metal Mixtures: Effect on PAH Induction of CYP1A1 in Human HepG2 Cells

Dilip D. Vakharia, Ning Liu, Ronald Pause, Michael Fasco, Erin Bessette, Qing-Yu Zhang, and Laurence S. Kaminsky

New York State Department of Health, Wadsworth Center, and the Department of Environmental Health and Toxicology, University at Albany, State University of New York, Albany, New York

Environmental polycyclic aromatic hydrocarbons (PAHs) and metals coexist, and such mixtures could affect the carcinogenicity of PAHs, possibly by modification of PAH induction of the PAH-bioactivating CYP1A. The effect on PAH-mediated CYP1A induction of arsenic, lead, mercury, or cadmium (ranked as the most hazardous environmental metals by the Environmental Protection Agency and the Agency for Toxic Substances and Disease Registry) has thus been investigated. Induction of CYP1A1 by benzo[a]pyrene (BAP), benzo[b]fluoranthene (BBF), dibenzo[a,h]anthracene (DBAHA), benzo[a]anthracene (BAA), or benzo[k]fluoranthene (BKF) was probed by ethoxyresorufin-O-deethylase activity (EROD) in 96-well plates of human HepG2 cells, by immunoblot analysis, and by reverse transcription-polymerase chain reaction. Cells rapidly took up PAHs (BAP, BKF) from medium; by 24 h only 14% remained in the medium, and no detectable PAH bound to well walls. Induction efficiency (relative to dimethyl sulfoxide controls) was in the order BKF (16-fold) > DBAHA (14-fold) > BAA (4-fold) > BAP (3-fold) > BBF (1-fold), all at 5 µM PAH. The metals did not markedly affect cell viability at concentrations of arsenic, 5 µM; lead, 50 µM; mercury, 5 µM; and cadmium, 5 µM. At 5 µM PAH concentration, all of the metals decreased levels of PAH-induced CYP1A1 activities (direct inhibition of EROD activity was excluded) by variable extents and in a PAH-dependent manner. With BAP as inducer decreases in induction were arsenic, 57%; cadmium, 82%; mercury, 4%; and lead, 20%. The decreases were not a consequence of transcriptional down-regulation. One possible conclusion is that these metals could diminish PAH carcinogenic potential by decreasing PAH-mediated induction of their bioactivation by CYP1A1.

Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Toxicol SciHome page
J. B. Silkworth, A. Koganti, K. Illouz, A. Possolo, M. Zhao, and S. B. Hamilton
Comparison of TCDD and PCB CYP1A Induction Sensitivities in Fresh Hepatocytes from Human Donors, Sprague-Dawley Rats, and Rhesus Monkeys and HepG2 Cells
Toxicol. Sci., October 1, 2005; 87(2): 508 - 519.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. Kann, M.-y. Huang, C. Estes, J. F. Reichard, M. A. Sartor, Y. Xia, and A. Puga
Arsenite-Induced Aryl Hydrocarbon Receptor Nuclear Translocation Results in Additive Induction of Phase I Genes and Synergistic Induction of Phase II Genes
Mol. Pharmacol., August 1, 2005; 68(2): 336 - 346.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. A. Bonzo, S. Chen, A. Galijatovic, and R. H. Tukey
Arsenite Inhibition of CYP1A1 Induction by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Is Independent of Cell Cycle Arrest
Mol. Pharmacol., April 1, 2005; 67(4): 1247 - 1256.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
E. E. Bessette, M. J. Fasco, B. T. Pentecost, and L. S. Kaminsky
MECHANISMS OF ARSENITE-MEDIATED DECREASES IN BENZO[K]FLUORANTHENE-INDUCED HUMAN CYTOCHROME P4501A1 LEVELS IN HEPG2 CELLS
Drug Metab. Dispos., March 1, 2005; 33(3): 312 - 320.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
N. Gharavi and A. O. S. El-Kadi
tert-BUTYLHYDROQUINONE IS A NOVEL ARYL HYDROCARBON RECEPTOR LIGAND
Drug Metab. Dispos., March 1, 2005; 33(3): 365 - 372.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
M. Miyata, E. Tamura, K. Motoki, K. Nagata, and Y. Yamazoe
Thalidomide-induced Suppression of Embryo Fibroblast Proliferation Requires CYP1A1-Mediated Activation
Drug Metab. Dispos., April 1, 2003; 31(4): 469 - 475.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
L. Vernhet, N. Allain, M. Le Vee, F. Morel, A. Guillouzo, and O. Fardel
Blockage of Multidrug Resistance-Associated Proteins Potentiates the Inhibitory Effects of Arsenic Trioxide on CYP1A1 Induction by Polycyclic Aromatic Hydrocarbons
J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 145 - 155.
[Abstract] [Full Text] [PDF]


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

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics.