Tandem mass spectrometry for the determination of deoxyribonucleic acid damage by polycyclic aromatic hydrocarbons: Plenary lecture

Tandem mass spectrometry (MS-MS) has proved to be a state-of-the-art technique for the structure of synthetic and biological compounds. One opportunity for MS-MS is the study of modified deoxyribonucleic acid (DNA) bases resulting from the attachment of carcinogens such as polycyclic aromatic hydrocarbons (PAHs). The determination of PAH-DNA adducts, formed in vivo via a one-electron oxidation or a diol-epoxide mechanism, requires high efficiency separation and very sensitive techniques. This is because the analyte will occur in complex biological mixtures and at low femtomole levels, considering that one modification occurs for 10⁶ or 10⁸ bases. This paper reviews various approaches to the separation and mass spectrometric structural determination of DNA adducts. The main emphasis of our research is the sub-picomolar detection and identification of DNA-PAH adducts, particularly those formed via a one-electron oxidation mechanism.