Gene expression profiles in rat liver slices exposed to hepatocarcinogenic enzyme inducers, peroxisome proliferators, and 17alpha-ethinylestradiol

Transcription profiling is used as an in vivo method for predicting the mode-of-action class of nongenotoxic carcinogens. To set up a reliable in vitro short-term test system DNA microarray technology was combined with rat liver slices. Seven compounds known to act as tumor promoters were selected,...

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Bibliographic Details
Published in:International journal of toxicology 2006-09, Vol.25 (5), p.379
Main Authors: Werle-Schneider, Gisela, Wölfelschneider, Andreas, von Brevern, Marie Charlotte, Scheel, Julia, Storck, Thorsten, Müller, Dieter, Glöckner, Reinhild, Bartsch, Helmut, Bartelmann, Matthias
Format: Article
Language:English
Subjects:
Androgen Antagonists - toxicity
Animals
Carcinogens - toxicity
Clofibric Acid - analogs & derivatives
Clofibric Acid - toxicity
Cyproterone Acetate - toxicity
Dehydroepiandrosterone - toxicity
Enzyme Induction
Estrogens - toxicity
Ethinyl Estradiol - toxicity
Fibric Acids
Gene Expression Profiling
Gene Expression Regulation - drug effects
In Vitro Techniques
Lindane - toxicity
Liver - drug effects
Liver - metabolism
Liver Neoplasms
Male
Oligonucleotide Array Sequence Analysis
Peroxisome Proliferators - toxicity
Phenobarbital - toxicity
Pyrimidines - toxicity
Rats
Rats, Wistar
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Summary:Transcription profiling is used as an in vivo method for predicting the mode-of-action class of nongenotoxic carcinogens. To set up a reliable in vitro short-term test system DNA microarray technology was combined with rat liver slices. Seven compounds known to act as tumor promoters were selected, which included the enzyme inducers phenobarbital, alpha-hexachlorocyclohexane, and cyproterone acetate; the peroxisome proliferators WY-14,643, dehydroepiandrosterone, and ciprofibrate; and the hormone 17alpha-ethinylestradiol. Rat liver slices were exposed to various concentrations of the compounds for 24 h. Toxicology-focused TOXaminer DNA microarrays containing approximately 1500 genes were used for generating gene expression profiles for each of the test compound. Hierarchical cluster analysis revealed that (i) gene expression profiles generated in rat liver slices in vitro were specific allowing classification of compounds with similar mode of action and (ii) expression profiles of rat liver slices exposed in vitro correlate with those induced after in vivo treatment (reported previously). Enzyme inducers and peroxisome proliferators formed two separate clusters, confirming that they act through different mechanisms. Expression profiles of the hormone 17alpha-ethinylestradiol were not similar to any of the other compounds. In conclusion, gene expression profiles induced by compounds that act via similar mechanisms showed common effects on transcription upon treatment in vivo and in rat liver slices in vitro.
ISSN:1091-5818