Mass spectrometric DNA adduct quantification by multiple reaction monitoring and its future use for the molecular epidemiology of cancer.

Abstract

The formation of DNA adducts is considered essential for tumor initiation. Quantification of DNA adducts may be achieved by various techniques of which LC-MS/MS-based multiple reaction monitoring has become the most prominent in the past decade. Adducts of single nucleosides are analyzed following enzymatic break-down of a DNA sample following adduct enrichment usually by solid-phase extraction. LC-MS/MS quantification is carried out using stable isotope-labeled internal reference substances. An upcoming challenge is the use of DNA adducts as biomarkers either for internal exposure to electrophilic genotoxins or for the approximation of cancer risk. Here we review recent studies in which DNA adducts were quantified by LC-MS/MS in DNA samples from human matrices. We outline a possible way for future research to aim at the development of an "adductome" approach for the characterization of DNA adduct spectra in human tissues. The DNA adduct spectrum reflects the inner exposure of an individual's tissue to electrophilic metabolites and, therefore, should replace the conventional and inaccurate external exposure in epidemiological studies in the future.