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Toxicity screening using biosensors that measure DNA damage.

James F Rusling1, Eli G Hvastkovs, John B Schenkman

  • 1Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269, USA. james.rusling@uconn.edu

Current Opinion in Drug Discovery & Development
|February 3, 2007
PubMed
Summary

New biosensors using DNA and enzymes offer a cost-effective method for early drug toxicity screening, specifically predicting genotoxicity by measuring DNA damage. This approach aids in minimizing late-stage drug development failures.

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Area of Science:

  • Biochemistry
  • Nanotechnology
  • Drug Development

Background:

  • Drug development failures are often caused by toxicity, necessitating early assessment.
  • Current toxicity testing is effective but costly; emerging biosensor technologies offer potential cost-effective alternatives.
  • Early toxicity screening is crucial to reduce economic losses from late-stage drug discontinuation.

Purpose of the Study:

  • To introduce and evaluate novel biosensor systems for early toxicity screening, focusing on genotoxicity prediction.
  • To highlight the advantages of biosensors employing DNA and metabolic enzymes for cost-effective drug safety assessment.
  • To compare these advanced biosensor technologies with other emerging toxicity screening methods.

Main Methods:

  • Development of biosensors utilizing thin films of DNA and metabolic enzymes (e.g., cytochrome P450s) as nanoreactors.
  • Detection of DNA damage via nucleobase-drug adduct formation using catalytic voltammetry capillary LC-MS or optical methods (electrochemiluminescence).
  • Monitoring oxidative stress using redox polymers specific for 8-oxoguanine; advanced arrays enable simultaneous multi-enzyme analysis.

Main Results:

  • Biosensors effectively measure DNA damage rates as a genotoxicity endpoint.
  • Optical and electrochemical detection methods provide sensitive assessment of drug-induced DNA damage.
  • Enzyme-based biosensor arrays allow for simultaneous relative genotoxicity assessment across multiple metabolic pathways.

Conclusions:

  • Biosensors integrating DNA and metabolic enzymes represent a promising, cost-effective approach for early genotoxicity screening.
  • This technology can significantly aid in identifying potential drug toxicity early in the development pipeline.
  • Advanced biosensor arrays offer efficient, simultaneous analysis, improving the speed and scope of toxicity assessments.