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Purification of Transcripts and Metabolites from Drosophila Heads
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Substantiate a read-across hypothesis by using transcriptome data-A case study on volatile diketones.

Christina Drake1, Matthias M Wehr1, Walter Zobl1

  • 1Fraunhofer Institute for Toxicology and Experimental Medicine, Chemical Safety and Toxicology, Hannover, Germany.

Frontiers in Toxicology
|May 19, 2023
PubMed
Summary
This summary is machine-generated.

Transcriptome data reveals shared mechanisms of action for diketones. Alpha-diketones show the most similar gene expression patterns, suggesting a common pathway for toxicity and supporting compound grouping strategies.

Keywords:
PBECTempO-seqnew approach methodologyprotein network analysisread acrosstranscriptomics

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Area of Science:

  • Toxicogenomics
  • Molecular Toxicology
  • Biomarker Discovery

Background:

  • Diacetyl, an alpha-diketone, is known to cause bronchiolitis obliterans.
  • Other diketones exhibit inflammatory and neuronal effects in preclinical studies.
  • Understanding shared mechanisms of action for diketone groups is crucial for risk assessment.

Purpose of the Study:

  • To evaluate the utility of transcriptome data in characterizing common mechanisms of action among short-chain aliphatic diketones.
  • To investigate early transcriptional responses in human bronchiolar cells exposed to diketones.
  • To support compound grouping and read-across approaches using biological profiles.

Main Methods:

  • Primary human bronchiolar epithelial cells (PBECs) were exposed to diketones.
  • Transcriptome analysis was performed using the Temp-O-Seq® EUToxRisk gene panel.
  • Differentially expressed genes (DEGs) were identified and analyzed for pathway enrichment and network interactions.
  • Master regulators (MRs) were identified and mapped to biological networks.

Main Results:

  • Transcriptome data revealed distinct and overlapping gene expression patterns among alpha-, beta-, and gamma-diketones.
  • Alpha-diketones exhibited highly concordant expression patterns, indicating a shared mode of action.
  • Pathway analysis showed a decrease in activated signaling pathways from alpha- to gamma-diketones.
  • Network analysis identified similar gene regulation related to fibrosis, inflammation, and apoptosis across diketone groups.

Conclusions:

  • Transcriptome data effectively characterizes shared mechanisms of action for diketone compounds.
  • The findings support the use of transcriptomics for assessing compound similarity and grouping.
  • This approach advances the understanding of diketone toxicity and aids in read-across applications.