Mechanism-based toxicogenomics (tgx) is used as a tool to identify markers reflective of the onset and progression of cholestasis in C57BL/6 mice using Cyclosporin A (CsA) as a model compound. Critical doses for tgx analysis were derived from a dose range finding study in which increase of serum cholesterol, total bile acids, and total bilirubin as well as induction of hepatocyte vacuolization 25 days upon repeated CsA administration through oral gavage were considered as critical effects. For tgx analysis to find early markers, livers of mice repeatedly treated with 3 mg/kg BW, 8.9 mg/kg BW, and 26.7 mg/kg BW for one, four, and eleven days were collected.
Overall design
60 samples are analyzed; per treatment duration (1, 4, 11 days), time-matched vehicle (olive oil) controls and three dose groups (3, 8.9, 26.7 mg/kg BW) were included; each group consisted of 5 replicates; 3 arrays were excluded, 2 because of quality control restrictions, 1 because of outlier properties. 2 that failed QC are omitted. Final data consists of 58 CEL files.
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