DNA adducts of chemical carcinogens

During the 30 years or so following the identification of the first pure chemical carcinogen (1), no common factors or pathways in the mechanism of action of carcinogens from different chemical classes were evident. For this reason perhaps, each class of carcinogen, e.g. the polycyclic aromatic hydrocarbons, the aromatic amines and the nitrosamines, was often reviewed and discussed separately. The discovery by the Millers and their colleagues of the role of metabolism in carcinogen activation (2) revealed a commonality amongst many carcinogens, i.e. a chemical reactivity towards cellular macromolecules, such as DNA (3,4). Today, DNA adduct formation is recognized as a common property of most potent carcinogens and the formation of such adducts is the basis of several current strategies in molecular epidemiology and biomonitoring. Despite this common aspect of mechanism for many chemical carcinogens, the complexities of metabolic activation and of the chemistry and stereochemistry of adduct formation have tended to keep some degree of compartmentalization in research and in literature reviews of DNA adduct formation by different classes of chemical compounds (5).