NDLI: Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas.

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Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas.

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Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Koo, P. Lee, G. Goldsmith, M. E. Myers, C. E. Farber, E. Cowan, K. H. Rushmore, T. Fairchild, C. R. Ivy, S. P.
Description	Author Affiliation: Fairchild CR ( Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD 20892.);
Abstract	We have previously reported the isolation of a human breast cancer cell line resistant to doxorubicin (adriamycin; AdrR MCF-7 cells) that has also developed the phenotype of multidrug resistance (MDR). MDR in this cell line is associated with increased expression of mdr (P glycoprotein) gene sequences. The development of MDR in AdrR MCF-7 cells is also associated with changes in the expression of several phase I and phase II drug-detoxifying enzymes. These changes are remarkably similar to those associated with development of xenobiotic resistance in rat hyperplastic liver nodules, a well-studied model system of chemical carcinogenesis. Using an mdr-encoded cDNA sequence isolated from AdrR MCF-7 cells, we have examined the expression of mdr sequences in rat livers under a variety of experimental conditions. The expression of mdr increased 3-fold in regenerating liver. It was also elevated (3- to 12-fold) in several different samples of rat hyperplastic nodules and in four of five hepatomas that developed in this system. This suggests that overexpression of mdr, a gene previously associated with resistance to antineoplastic agents, may also be involved in the development of resistance to xenobiotics in rat hyperplastic nodules. In addition, although the acute administration of 2-acetylaminofluorene induced an 8-fold increase in hepatic mdr-encoded RNA, performance of a partial hepatectomy either before or after administration of 2-acetylaminofluorene resulted in a greater than 80-fold increase in mdr gene expression over that in normal untreated livers. This represents an important in vivo model system in which to study the acute regulation of this drug resistance gene.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	21
Volume Number	84
Language	English
Publisher	National Academy of Sciences
Publisher Date	1987-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	2-Acetylaminofluorene Toxicity Liver Neoplasms, Experimental Pathology Oncogenes Drug Effects Precancerous Conditions Chemically Induced Transcription, Genetic Animals Breast Neoplasms Cell Line DNA Isolation & Purification Doxorubicin Pharmacology Drug Resistance Liver Regeneration Membrane Glycoproteins Genetics P-Glycoprotein Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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