Stable-isotope-dilution tandem mass spectrometry is the most advanced technique used
for quantitative determination of a wide spectrum of endogenously generated DNA nucleobase
modifications. It is regarded as a gold standard for such analyses. Here, we consider
the requirements for reliable identification and quantification of DNA adducts/modifications,
whether endogenously derived or not, and discuss how their quantification can provide
information on the mechanism of action and the biological relevance of individual
nucleobase modifications. A clinical application of such measurements will only be
possible after a full validation of the assay and once we have gained a better understanding
of the exact role that these DNA modifications play in disease pathogenesis. Once
these prerequisites are satisfied, DNA modification measurements may be helpful as
clinical parameters for treatment monitoring, for risk group identification and for
the development of prevention strategies.
