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Toxicogenomics on mice liver of coumarins from Calophyllum brasiliense

ABSTRACT: A toxicogenomic analysis from liver of different pharmacological active coumarins (mammea A/BA+A/BB 3:1 and soulatrolide ) was performed on mice treated (20mg/kg/daily) for a whole week to evaluate if such compounds possess or could develop a hazardous profile on liver. In this dataset, we include the expression data obtained from dissected liver mouse treated with active coumarins (obtained from Calophyllum brasiliense) and control (SSI) for a whole week. Livers from 4 animals per treatment and control were subjected to RNA extraction. These data showed 46 genes up and 72 downregulated genes for mammea coumarins and 665 up and 1077 downregulated genes .

ORGANISM(S): Mus musculus

PROVIDER: GSE72755 | GEO | 2015/09/06

SECONDARY ACCESSION(S): PRJNA294842

REPOSITORIES: GEO

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Project description:The application of toxicogenomics as a predictive tool for chemical risk assessment has been under evaluation by the toxicology community for more than a decade. However, toxicogenomics predominately remains a tool for investigative research rather than for regulatory risk assessment. In this study, we aimed to determine whether the current generation of microarray technology in combination with an in vitro experimental design was capable of generating robust, reproducible data of sufficient quality to show promise as a tool for regulatory risk assessment. To this end, we designed a prospective collaborative study to determine the level of inter- and intra-laboratory reproducibility between three independent laboratories. All test sites adopted the same protocols for all aspects of the toxicogenomic experiment including cell culture, chemical exposure, RNA extraction, microarray data generation and analysis. As a case study, the genotoxic carcinogen B[a]P and the human hepatocyte cell line HepG2 were used to generate three comparable toxicogenomic data sets. High levels of technical reproducibility were demonstrated using a widely employed gene expression microarray platform. While differences at the global transcriptome level were still observed between the test sites, a common subset of B[a]P responsive genes was identified across all test sites which included both genes previously reported in the literature as B[a]P responsive in addition to the same most highly up and down regulated genes. Pending further analysis, these preliminary data show promise that the current generation of microarray technology in combination with a standard in vitro experimental design can produce robust data that can be reproducibly generated in independent laboratories. Future work will need to determine whether in vitro model(s) can be not only reproducible but also predictive for a range of toxic chemicals with different mechanisms of action. Such an approach may potentially be part of future in vitro testing regimes for regulatory risk assessment.

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Toxicogenomics on mice liver of coumarins from Calophyllum brasiliense

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