Effect of the difference in vehicles on gene expression in the rat liver--analysis of the control data in the Toxicogenomics Project Database.
The Toxicogenomics Project is a 5-year collaborative project by the Japanese government and pharmaceutical companies in 2002. Its aim is to construct a large-scale toxicology database of 150 compounds orally administered to rats. The test consists of a single administration test (3, 6, 9 and 24 h) and a repeated administration test (3, 7, 14 and 28 days), and the conventional toxicology data together with the gene expression data in liver as analyzed by using Affymetrix GeneChip are being accumulated. In the project, either methylcellulose or corn oil is employed as vehicle. We examined whether the vehicle itself affects the analysis of gene expression and found that corn oil alone affected the food consumption and biochemical parameters mainly related to lipid metabolism, and this accompanied typical changes in the gene expression. Most of the genes modulated by corn oil were related to cholesterol or fatty acid metabolism (e.g., CYP7A1, CYP8B1, 3-hydroxy-3-methylglutaryl-Coenzyme A reductase, squalene epoxidase, angiopoietin-like protein 4, fatty acid synthase, fatty acid binding proteins), suggesting that the response was physiologic to the oil intake. Many of the lipid-related genes showed circadian rhythm within a day, but the expression pattern of general clock genes (e.g., period 2, arylhydrocarbon nuclear receptor translocator-like, D site albumin promoter binding protein) were unaffected by corn oil, suggesting that the effects are specific for lipid metabolism. These results would be useful for usage of the database especially when drugs with different vehicle control are compared.
Takashima
Kayoko
K
Toxicogenomics Project, National Institute of Health Sciences, Setagaya-Ku, Tokyo, 158-8501, Japan.
Mizukawa
Yumiko
Y
Morishita
Katsumi
K
Okuyama
Manabu
M
Kasahara
Toshihiko
T
Toritsuka
Naoki
N
Miyagishima
Toshikazu
T
Nagao
Taku
T
Urushidani
Tetsuro
T
D000818:Animals; D003314:Corn Oil / Q000494:pharmacology; D030541:Databases, Genetic; D015870:Gene Expression / Q000187:drug effects*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008747:Methylcellulose / Q000494:pharmacology; D008838:Microcomputers; D020411:Oligonucleotide Array Sequence Analysis; D014677:Pharmaceutical Vehicles / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D043922:Toxicogenetics
D014677:Pharmaceutical Vehicles; D012313:RNA; D003314:Corn Oil; D008747:Methylcellulose