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