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In vivo murine hepatic microRNA and mRNA expression signatures predicting the (non-)genotoxic carcinogenic potential of chemicals
- Source :
- Archives of Toxicology, 88(4), 1023-1034, Archives of Toxicology, Archives of toxicology = Archiv für Toxikologie, 88(4), 1023-1034. Springer Verlag, Archives of Toxicology, 88(4), 1023-1034. Springer-Verlag
- Publication Year :
- 2014
-
Abstract
- There is a high need to improve the assessment of, especially non-genotoxic, carcinogenic features of chemicals. We therefore explored a toxicogenomics-based approach using genome-wide microRNA and mRNA expression profiles upon short-term exposure in mice. For this, wild-type mice were exposed for seven days to three different classes of chemicals, i.e., four genotoxic carcinogens (GTXC), seven non-genotoxic carcinogens (NGTXC), and five toxic non-carcinogens. Hepatic expression patterns of mRNA and microRNA transcripts were determined after exposure and used to assess the discriminative power of the in vivo transcriptome for GTXC and NGTXC. A final classifier set, discriminative for GTXC and NGTXC, was generated from the transcriptomic data using a tiered approach. This appeared to be a valid approach, since the predictive power of the final classifier set in three different classifier algorithms was very high for the original training set of chemicals. Subsequent validation in an additional set of chemicals revealed that the predictive power for GTXC remained high, in contrast to NGTXC, which appeared to be more troublesome. Our study demonstrated that the in vivo microRNA-ome has less discriminative power to correctly identify (non-)genotoxic carcinogen classes. The results generally indicate that single mRNA transcripts do have the potential to be applied in risk assessment, but that additional (genomic) strategies are necessary to correctly predict the non-genotoxic carcinogenic potential of a chemical.
- Subjects :
- Genetic Markers
Male
Time Factors
Health, Toxicology and Mutagenesis
Mrna expression
Computational biology
Biology
Toxicology
Bioinformatics
Toxicogenetics
Transcriptome
Mice
In vivo
microRNA
Gene expression
Animals
RNA, Messenger
Carcinogen
Risk assessment
Messenger RNA
Gene Expression Profiling
Discriminant Analysis
Reproducibility of Results
MicroRNA
General Medicine
Genotoxic and non-genotoxic carcinogen
Biomarker
Classification
Mice, Inbred C57BL
MicroRNAs
Gene Expression Regulation
Liver
Carcinogens
Toxicogenomics
Algorithms
Mutagens
Subjects
Details
- Language :
- English
- ISSN :
- 03405761
- Volume :
- 88
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Archives of toxicology = Archiv für Toxikologie
- Accession number :
- edsair.doi.dedup.....3743d418383254aa3622f5ca4061e7bd