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.