Transcriptomics

Dataset Information

14

Transcription profiling by array of primary mouse hepatocytes after treatment with various genotoxic and non-genotoxic carcinogens


ABSTRACT: The prediction of possible carcinogenicity of chemicals for humans represents an ongoing challenge. Chronic rodent bioassays predict human cancer risk at only limited reliability while simultaneously being expensive and long-lasting. In order to seek for alternatives, in the present study, the ability of a transcriptomics-based primary mouse hepatocyte model to classify carcinogens by their modes of action was evaluated. As it is obvious that exposure will induce a cascade of gene expression modifications, in particular, the influence of exposure time in vitro on discriminating genotoxic (GTX) carcinogens from non-genotoxic (NGTX) carcinogens class prediction was investigated. Primary mouse hepatocytes from male C57Bl6 mice were treated for 12, 24, 36 and 48 h with two GTX and two NGTX carcinogens. For the purpose of validation, two additional GTX compounds were studied after incubation periods of 24 and 48 h. Immunostaining of ?H2AX foci was applied to phenotypically verify DNA damage. Whole genome gene expression modifications were analyzed by means of Affymetrix mouse genome 430 2.0 microarrays. Datasets were normalized using RMA and differentially expressed genes were selected for assessing class prediction. The ?H2AX assay confirmed significant induction of DNA damage after treatment with GTX compounds, whereas NGTX compounds showed no activity beyond background levels. Discrimination of GTX and NGTX carcinogens by Prediction Analysis of Microarray (PAM) was validated and resulted in a perfect classification. The present study shows that gene expression profiling in primary mouse hepatocytes is promising for discriminating between GTX and NGTX compounds and that this classification improves with increasing treatment period.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Mus musculus  

SUBMITTER: Danyel Jennen  

PROVIDER: E-MEXP-2209 | ArrayExpress | 2010-06-09

REPOSITORIES: ArrayExpress

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Publications

Discrimination for genotoxic and nongenotoxic carcinogens by gene expression profiling in primary mouse hepatocytes improves with exposure time.

Mathijs Karen K   Brauers Karen J J KJ   Jennen Danyel G J DG   Boorsma Andre A   van Herwijnen Marcel H M MH   Gottschalk Ralph W H RW   Kleinjans Jos C S JC   van Delft Joost H M JH  

Toxicological sciences : an official journal of the Society of Toxicology 20090921 2


Assessing the potential carcinogenicity of chemicals for humans represents an ongoing challenge. Chronic rodent bioassays predict human cancer risk at only limited reliability and are simultaneously expensive and long lasting. In order to seek for alternatives, the ability of a transcriptomics-based primary mouse hepatocyte model to classify carcinogens by their modes of action was evaluated. As it is obvious that exposure will induce a cascade of gene expression modifications, in particular, th  ...[more]

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