JPET Introducing ALZET?ew Model 2006 Pump

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
Right arrow Citation Map
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 Moorthy, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moorthy, B.

Vol. 294, Issue 1, 313-322, July 2000

Persistent Expression of 3-Methylcholanthrene-Inducible Cytochromes P4501A in Rat Hepatic and Extrahepatic Tissues1

Bhagavatula Moorthy

Department of Pediatrics, Baylor College of Medicine, Houston, Texas

We reported earlier that 3-methylcholanthrene (MC) persistently induces hepatic ethoxyresorufin O-deethylase activities (CYP1A1) in rats for up to 45 days. In this investigation, we tested the hypotheses that persistent expression of CYP1A1 activities is paralleled by sustained induction of CYP1A1/CYP1A2 apoproteins and their mRNAs and that this phenomenon is mediated by mechanisms other than retention of MC in the rat. Rats were given MC (93 µmol/kg) i.p., once daily for 4 days, and CYP1A1/1A2 parameters were measured in liver at selected time points. MC-elicited increases in CYP1A1/1A2 activities, apoprotein contents, and mRNA levels were sustained for several weeks after the last dose of MC treatment. MC also caused long-term induction of CYP1A1 in lungs and mammary glands. Rats treated with [3H]MC once daily for 4 days excreted 92.3% of the administered radioactivity in feces and urine by day 15. The intrahepatic concentration of MC at the 15-day time point was 270 pmol/g. Dose-response studies showed that administration of MC (2 µmol/kg), which produced an intrahepatic concentration of 271 pmol/g after 24 h, did not induce CYP1A1/1A2 activities, strongly suggesting that the sustained induction of CYP1A1/1A2 was not due to retention of the parent MC in the body. Electrophoretic mobility shift assays revealed that persistent CYP1A1 induction by MC involved Ah receptor-independent mechanisms. In conclusion, our results support the hypothesis that persistent expression of CYP1A1/1A2 by MC is mediated by mechanisms independent of the retention of the parent carcinogen.

1 This work was supported in part by U.S. Public Health Service (USPHS) Grant ES09132 from the National Institute of Environmental Health Sciences and a grant-in-aid from the American Heart Association (Texas Affiliate) to B. Moorthy and by USPHS Grant CA32157 from the National Cancer Institute to Kurt Randerath.

0022-3565/00/2941-0313$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Toxicol SciHome page
S. R. Kondraganti, W. Jiang, A. K. Jaiswal, and B. Moorthy
Persistent Induction of Hepatic and Pulmonary Phase II Enzymes by 3-Methylcholanthrene in Rats
Toxicol. Sci., April 1, 2008; 102(2): 337 - 344.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. E. Bohonowych and M. S. Denison
Persistent Binding of Ligands to the Aryl Hydrocarbon Receptor
Toxicol. Sci., July 1, 2007; 98(1): 99 - 109.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
X. I. Couroucli, Y. W. Liang, W. Jiang, R. Barrios, and B. Moorthy
Attenuation of Oxygen-Induced Abnormal Lung Maturation in Rats by Retinoic Acid: Possible Role of Cytochrome P4501A Enzymes
J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 946 - 954.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
A. Sinha, K. Muthiah, W. Jiang, X. Couroucli, R. Barrios, and B. Moorthy
Attenuation of Hyperoxic Lung Injury by the CYP1A Inducer {beta}-Naphthoflavone
Toxicol. Sci., September 1, 2005; 87(1): 204 - 212.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
W. Jiang, S. E. Welty, X. I. Couroucli, R. Barrios, S. R. Kondraganti, K. Muthiah, L. Yu, S. E. Avery, and B. Moorthy
Disruption of the Ah Receptor Gene Alters the Susceptibility of Mice to Oxygen-Mediated Regulation of Pulmonary and Hepatic Cytochromes P4501A Expression and Exacerbates Hyperoxic Lung Injury
J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 512 - 519.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. R. Kondraganti, W. Jiang, and B. Moorthy
Differential Regulation of Expression of Hepatic and Pulmonary Cytochrome P4501A Enzymes by 3-Methylcholanthrene in Mice Lacking the CYP1A2 Gene
J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 945 - 951.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
X. I. Couroucli, S. E. Welty, R. S. Geske, and B. Moorthy
Regulation of Pulmonary and Hepatic Cytochrome P4501A Expression in the Rat by Hyperoxia: Implications for Hyperoxic Lung Injury
Mol. Pharmacol., March 1, 2002; 61(3): 507 - 515.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
B. Moorthy, K. P. Miller, W. Jiang, and K. S. Ramos
The atherogen 3-methylcholanthrene induces multiple DNA adducts in mouse aortic smooth muscle cells: role of cytochrome P4501B1
Cardiovasc Res, March 1, 2002; 53(4): 1002 - 1009.
[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 © 2000 by the American Society for Pharmacology and Experimental Therapeutics.