An evaluation of a low-density DNA microarray using cytochrome P450 inducers

被引:17
作者
Meneses-Lorente, G
de Longueville, F
Dos Santos-Mendes, S
Bonnert, TP
Jack, A
Evrard, S
Bertholet, V
Pike, A
Scott-Stevens, P
Remacle, J
Sohal, B
机构
[1] Merck Sharp & Dohme Ltd, Neurosci Res Ctr, Harlow CM20 2QR, Essex, England
[2] Univ Namur, Lab Biochem & Cellular Biol, Namur, Belgium
[3] Univ Namur, Dept Math, Stat Unit, Namur, Belgium
关键词
D O I
10.1021/tx034117n
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The aim of this study was to validate a low-density DNA microarray "Rat HepatoChip", which contains 59 genes from a range of potential toxic markers and drug metabolism-related genes. Liver mRNA was isolated from rats dosed with six different chemicals, dexamethasone, troleandomycin, miconazole, clotrimazole, and methylelofanapate, which are all known to induce different cytochrome P450 genes, and isoniazid, which does not cause histopathological changes. Replicate microarrays were used to measure the variability in the chips and in the process. The average variability in signal between different chips observed in triplicate experiments was 33% ranging from 21 to 39% depending on genes. We also demonstrated a strong correlation between the liver histopathology and the gene expression profiles indicating that the gene expression profile reflects histopathological changes. These results suggest that the Rat HepatoChip microarray may provide a fast and effective tool for assessing the toxicity profile of developmental drug candidates during the drug discovery process.
引用
收藏
页码:1070 / 1077
页数:8
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