Capillary Electrophoresis-Mass Spectrometric Analysis of DNA Adducts

It is believed that the majority of cancers are caused by contact with naturally occurring or synthetic chemicals present in the environment. Hence, in theory, if contact with these carcinogens is minimized or eliminated, most cancers could be preventable (
1
). Cancer is a multistage process in which the first stage is called initiation. It is during the initiation stage that chemical damage or modification occurs to
DNA
(
2
). The compounds, which result from a covalent attachment of the chemical with DNA, are called “DNA adducts.” Because of their potential for initiating cancer, the characterization and quantitation of DNA adducts are important. The specific identification of the adduct compound, the position of the adduct group on the base and the location of the modified base in the DNA sequence are significant factors. Carcinogens vary from the highly reactive to relatively inert, however they are typically electrophilic in nature or become electrophilic after being metabolized in vivo (
1
,
2
). The most reactive sites are the purine nitrogens of guanine and adenine (
1
). These nucleophilic sites are ideal for covalent reactions with electrophilic carcinogens. DNA adduct formation is complex, but there is site selectivity or specificity (
2
).