A DNA-conjugated magnetic nanoparticle assay for assessing genotoxicity.
The genotoxicity of a molecule refers to its ability to interact with DNA in a way that inhibits normal DNA replication and transcription possibly leading to mutagenesis or carcinogenesis. Assessing the genotoxicity of a compound is critical in the development of pharmaceuticals and other products designed for human consumption or use. Typically genotoxicity is established using expensive and time consuming methods using animals or bacteria like the Ames test, mouse lymphoma assay, or mouse and rat carcinogenicity tests. We have developed a magnetic nanoparticle-based assay that uses conjugated double-stranded DNA to serve as a substrate for interaction with genotoxic molecules. After application of a magnetic field, the genotoxic molecules are extracted with the DNA-conjugated magnetic nanoparticles. The genotoxic molecules can then be released and detected. To evaluate the potential of this assay, we have screened several genotoxic and non-genotoxic compounds and have demonstrated the ability to extract a genotoxic compound in the presence of a non-genotoxic molecule. The assay demonstrates suitable analytical performance and the ability to differentiate between genotoxic and non-genotoxic molecules providing a rapid and inexpensive alternative to more traditional methods of evaluating genotoxicity.
Genentech Inc., Small Molecule Pharmaceutical Sciences, 1 DNA Way, South San Francisco, CA 94080, USA. medley.colin@gene.com
Colin D
CD
Medley
Joshua E
JE
Smith
Larry S
LS
Wigman
Nik P
NP
Chetwyn
D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D000077143:Docetaxel; D004317:Doxorubicin / Q000737:chemistry; D004996:Ethidium / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry; D008280:Magnetics; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry; D013499:Surface Properties; D043823:Taxoids / Q000737:chemistry
D009153:Mutagens; D043823:Taxoids; D000077143:Docetaxel; D012822:Silicon Dioxide; D004317:Doxorubicin; D004247:DNA; D004996:Ethidium; D007213:Indomethacin