title: A newly developed DNA microarray is useful to assess induction of cytochromes p450 in the cynomolgus monkey.
abstract: Cytochromes P450 (P450s or CYPs) are a gene family of highly homologous genes and include the CYP1-4 family, which is relevant to drug metabolism. In the cynomolgus monkey (which is frequently used in drug metabolism studies), numerous CYPs (mfCYPs) have been identified in the CYP1-4 family. DNA microarrays are useful for high-throughput screening assays; however, there is a potential problem with cross-hybridization of highly homologous genes in the gene family. This problem might be solved with the use of low-density DNA microarrays, with which specific validation can be performed for the genes on the microarray. We have developed a DNA microarray for the 20 mfCYPs and have evaluated and validated its specificity and usefulness. First, in both DNA microarray and quantitative polymerase chain reaction (qPCR) analyses, hepatic expression of each mfCYP correlated well, and similar tissue expression patterns were observed for five representative mfCYPs, confirming the specificity of the DNA microarray. Second, the usefulness of this DNA microarray was validated by induction analysis of mfCYPs in primary hepatocytes, which successfully detected known responders, but also novel responders (mfCYP2C43, mfCYP2C75, and mfCYP3A5 for rifampicin), as confirmed by qPCR analysis. This DNA microarray can thus be utilized for high-throughput assays during drug development.
authors.affiliation: Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Ise
authors.forename: Shotaro
authors.initials: S
authors.lastname: Uehara
authors.forename: Hideo
authors.initials: H
authors.lastname: Akiyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Nagata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nobumasa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uno
mesh_terms: D000825:Animal Structures / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004790:Enzyme Induction / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007082:Ileum / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics; D007583:Jejunum / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008252:Macaca fascicularis / Q000235:genetics / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D009853:Omeprazole / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D009853:Omeprazole; D012293:Rifampin