DNA Adducts Discovery Test/Epigenetics

DNA Adducts Discovery Test

Summary

Trace Bio Analytics provides a unique discovery/characterization assay for DNA adducts (genotoxicity in the form of damaged nucleotides in DNA). This assay is termed the “DNA Adducts Discovery Test” and is based on isotopologue-enhanced mass spectrometry.

Background

Conventional genotoxicity tests, such as the Ames test and the micronucleus assay, yield useful but vague information about genotoxicity.  The DNA Adducts Discovery Test gives specific chemical information.

Isotopologue-Enhanced Mass Spectrometry

The assay for genotoxicity that is available from Trace Bio Analytics utilizes an isotopologue mass tag pair in combination with mass spectrometry. The isotopologue pair enhances the performance of mass spectrometry for broad detection and structural characterization of DNA adducts.  This means that many DNA adducts are discovered and analyzed simultaneously. Even the genotoxicity of chemical mixtures can be defined in a specific way.

Questions that the DNA Adducts Discovery Test Can Answer

Exactly what is causing this positive result in my Ames test? By answering this question, the DNA Adducts Discovery Test can rescue a genotoxic drug candidate by specifying the chemical species that has adducted onto the DNA, thus providing critical guidance for modifying the structure of the drug.

Does this chemical mixture pose a genotoxicity risk, and, if so, what are the causative chemicals? Samples such as air, smoke, water, soil, dust, cosmetics, household chemicals, drugs and food products can be evaluated for genotoxicity by the DNA Adducts Discovery Test in combination with a DNA-exposure experiment.

Does genotoxicity play a role in the particular condition or disease process that my lab is studying?  While genotoxicity is a known factor in cancer, it may contribute to other conditions such as aging, autism, dementia, diabetes and heart disease.  The DNA Adducts Discovery Test potentially can help in defining the contribution of DNA damage.

Can cancer risk be reduced by lowering blood DNA adducts?  To answer this question, DNA adducts need to be discovered and structurally-characterized broadly with ultra-high sensitivity.  The second generation DNA Adducts Discovery Test is being developed by Trace Bio Analytics as a potential Cancer Prevention Test . 

Application to Methylcytosine Epigenetic Profiling 

The DNA Adduct Discovery Test simultaneously measures 5-methylcytosine, 5-hydroxymethyl cytosine, 5-formylcytosine and 5-carboxycytosine in DNA.  This profiles the level and erasure of the epigenetic methyl mark on DNA, and thereby helps in understanding the potential role of these metabolites of 5-methylcytosine in the epigenetic control of gene expression.