Gene expression analysis of peroxisome proliferators- and phenytoin-induced hepatotoxicity using cDNA microarray.
The recent DNA microarray technology enables us to understand a large number of gene expression profiling. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, the toxicogenomics through this technology may be very powerful for understanding the effect of unknown toxic mechanisms in biological system. We have studied that the effect of compounds related to hepatotoxin in vivo system using DNA microarray and classified chemicals which have been well characterized. We have studied three compounds; 2 peroxisome proliferators: Clofibrate (ethyl-p-chlorophenoxyisobutyrate), gemfibrozil (5-2[2,5-dimethyl-phenoxy]2-2-dimethyl-pentanonic), and an antiepileptic drug: phenytoin (5,5-diphenylhydantoin). Male Sprague-Dawely VAF(+) albino rats of 5-6 weeks old were treated with each compound for 24 hr and 2 weeks. 4.8 K cDNA microarray in house has been used for gene expression profiling. We found that the clustering of gene expression had similarity like as the toxic phenotype of compounds.
Jung
Jin-Wook
JW
Department of Biochemistry and Molecular Biology, Hanyang University & Genocheck Co., Ltd., South Korea.
Park
Joon-Suk
JS
Hwang
Jae-Woong
JW
Kang
Kyung-Sun
KS
Lee
Yong-Soon
YS
Song
Bog-Soo
BS
Lee
Gyoung-Jae
GJ
Yeo
Chan-Dong
CD
Kang
Jong-Soo
JS
Lee
Wan-Seon
WS
Jeon
Ki-Seon
KS
Um
Chan-Hwi
CH
Kim
Yang-Suk
YS
Oh
Moon-Ju
MJ
Youn
Jong-Pil
JP
Li
Peng
P
Park
Jung-Eun
JE
Hwang
Seung Yong
SY
D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D002994:Clofibrate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015248:Gemfibrozil / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism; D010672:Phenytoin / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D010672:Phenytoin; D002994:Clofibrate; D015248:Gemfibrozil