ABSTRACT
Alkylating agents from both exogenous and endogenous sources constantly modify DNA (1-12). Alkylating agents are found in plants, foods, and are produced industrially. Sources of endogenous alkylation include nitrosating agents and lipoperoxidation (1,3,12,13). The sites of modification on DNA bases are the same for all alkylating agents (Fig. 1a) and include all the exocyclic nitrogens and oxygens. Ring nitrogens without hydrogens (N7-G, N3-A, N1-A, N3-C, N7-A) are also targets for alkylation. In addition to alterations of DNA bases, the phosphodiester linkages can be converted to phosphotriesters (Fig. 1b). Although the modification sites are the same, the percentage of modification at each site depends on the specific alkylating agent. The damage resulting from bulky alkylating agents is generally removed by NER, but many less bulky modifications of DNA (groups with formula weights ca. 40 g/mol) are removed by at least five different types of repair. Prior to discussion of the mechanisms of recognition, a brief introduction regarding the generation of these damage sites is appropriate.
