Expression analysis of early response-related genes in rat liver epithelial cells exposed to thioacetamide in vitro.
Thioacetamide (TA) is a potent hepatotoxicant known to affect liver metabolism, inhibit mRNA transport and induce immune suppression. The genetic mechanism underlining this biological toxic compound is well understood using microarray technology. Thus, we used high-throughput rat genome oligonucleotide microarrays containing approximately 22,000 genes to investigate the genetic components of TA-related cytotoxicity in WB-F344 rat liver epithelial (WB-F344) cells. We treated cells with TA (two concentrations over five time periods, ranging from 1 to 24 hr), isolated total RNA at 1, 3, 6, 12 and 24 hr following TA treatment and hybridized the RNA to microarrays. Clustering analysis distinguished two groups of genes, early (1 and 3 hr) and late (6, 12 and 24 hr) phase genes. In total, 2,129 and 2,348 differentially-expressed genes were identified following treatment with low and high concentrations of TA, respectively. A common set of 1,229 genes that were differentially expressed following treatment with both low (1,000 muM) and high (10,000 muM) concentrations of TA had similar expression patterns. Interestingly, 1,410 genes at the low concentration and 1,858 genes at the high concentration were differentially expressed in the early phases, suggesting that these genes associated with the early response to TA may be useful as early markers of hepatotoxicity.
Yeom
Hye-Jung
HJ
Department of Biochemistry, Hanyang University & GenoCheck Co., Ltd., Sangrok-gu, Ansan, Gyeonggi-do 426-791, South Korea.
Park
Joon-Suk
JS
Oh
Moon-Ju
MJ
Paul
Saswati
S
Kim
Joo Kyoung
JK
Kim
Seung Jun
SJ
Lee
Yong-Soon
YS
Kang
Kyung-Sun
KS
Hwang
Seung Yong
SY
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013853:Thioacetamide / Q000633:toxicity*
D013853:Thioacetamide