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ADME PK

Toxicological gene regulation*

  • Toxicogenomics is the application of transcription profiling to toxicology. It is often used to predict toxicity before functional damage is observed and is based on the assumption that compounds which elicit toxicity through similar mechanisms have particular signatures of gene expression.
  • One example of where gene expression profiles have been successfully linked to toxicity is the assessment of oxidative stress-associated hepatotoxicity related to a single specific mechanism1,2.
  • Real Time quantitative Reverse Transcription PCR (qRT-PCR) is one of the most sensitive techniques for mRNA detection and quantitation and is used to confirm results from microarray analysis.
  • Cyprotex have purchased an Applied Biosystems 7900HT system and have the ability to monitor the expression of a wide range of different toxicologically relevant genes using qRT-PCR.
Because genomic biomarkers are frequently more sensitive than the traditional, functional and morphological markers, they represent a useful supplement to more reliably detect hepatotoxicity in short term studies, where the full phenotypic manifestation of toxicity may not have fully developed.

3 Blomme EAG, Yang Y, Waring JF (2009) Toxicology Letters 186; 22–31

*This is a custom service. Please contact us about your requirements.

References

1 McMillian M et al. (2004) Biochem Pharmacol 67; 2141–2165
2 McMillian M et al. (2004) Biochem Pharmacol 68; 2249–2261
3 Blomme EAG et al. (2009) Toxicology Letters 186; 22–31

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