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Research ArticleArticle

Detection of Cytochrome P450 and Other Drug-Metabolizing Enzyme mRNAs in Peripheral Blood Mononuclear Cells Using DNA Arrays

Linh T. Nguyen, Murali Ramanathan, Bianca Weinstock-Guttman, Kiran Dole, Colleen Miller, Margaret Planter, Kara Patrick, Carol Brownscheidle and Lawrence D. Jacobs
Drug Metabolism and Disposition August 2000, 28 (8) 987-993;
Linh T. Nguyen
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Murali Ramanathan
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Bianca Weinstock-Guttman
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Kiran Dole
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Colleen Miller
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Margaret Planter
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Kara Patrick
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Carol Brownscheidle
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Lawrence D. Jacobs
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Abstract

The purpose of this study was to determine whether the expression of cytochrome P450 (CYP) enzyme mRNAs, other drug-metabolizing enzyme mRNAs, and transporter mRNAs can be detected using DNA arrays. Total RNA was isolated from peripheral blood mononuclear cells of 10 multiple sclerosis patients and 10 age- and sex-matched controls. The mRNA was reverse transcribed to radiolabeled cDNA, and the resultant cDNA was used to probe a DNA array containing several thousand known human genes. The signals corresponding to several CYPs, drug-metabolizing, and transporter mRNAs was substantially above background. The results demonstrate that the DNA array technique has the sensitivity and the selectivity for applications in the pharmaceutical sciences. The mean values for mRNAs of specific CYPs and drug-metabolizing enzymes in peripheral blood cells were compared with reported values for liver. The capabilities of DNA arrays may prove useful for characterizing CYP expression in a variety of clinical samples.

Footnotes

  • Send reprint requests to: Dr. Murali Ramanathan, Department of Pharmaceutics, 543 Cooke Hall, State University of New York at Buffalo Buffalo, NY 14260-1200. E-mailmurali{at}acsu.buffalo.edu

  • This work was supported by Grants RG2739A1 from the National Multiple Sclerosis Society and R29GM54087 from the National Institute of General Medical Sciences.

  • Abbreviations used are::
    CYP
    cytochrome P450
    PCR
    polymerase chain reaction
    MS
    multiple sclerosis
    IFN
    interferon
    UGT
    uridine diphosphate glucuronosyl transferase
    COMT
    catecholamine-O-methyltransferase
    GST
    glutathioneS-transferase
    MDR
    multidrug resistance
    MRP
    multidrug resistance-associated protein
    • Received December 22, 1999.
    • Accepted June 5, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 28 (8)
Drug Metabolism and Disposition
Vol. 28, Issue 8
1 Aug 2000
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Research ArticleArticle

Detection of Cytochrome P450 and Other Drug-Metabolizing Enzyme mRNAs in Peripheral Blood Mononuclear Cells Using DNA Arrays

Linh T. Nguyen, Murali Ramanathan, Bianca Weinstock-Guttman, Kiran Dole, Colleen Miller, Margaret Planter, Kara Patrick, Carol Brownscheidle and Lawrence D. Jacobs
Drug Metabolism and Disposition August 1, 2000, 28 (8) 987-993;

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Research ArticleArticle

Detection of Cytochrome P450 and Other Drug-Metabolizing Enzyme mRNAs in Peripheral Blood Mononuclear Cells Using DNA Arrays

Linh T. Nguyen, Murali Ramanathan, Bianca Weinstock-Guttman, Kiran Dole, Colleen Miller, Margaret Planter, Kara Patrick, Carol Brownscheidle and Lawrence D. Jacobs
Drug Metabolism and Disposition August 1, 2000, 28 (8) 987-993;
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