Induction of Deoxyribonucleic Acid Damage by Alkylating Agents
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Alkylating agents are a series of potentially carcinogenic compounds that are able to introduce lesions into deoxyribonucleic acid (DNA; ref. 1 ). For their electrophilic nature, alkylating agents have an affinity for the nucleophilic centers of DNA and are monofunctional (have one reactive group) or bifunctional (have two reactive groups). Alkylating agents, such as methylmethanesulphonate and N -ethyl-N -nitrosourea, introduce methyl, ethyl, and complicated alkyl groups to the functional groups of nucleic acid bases, with ring nitrogens being generally more reactive than ring oxygens (2 –4 ). The alkylation of oxygen in phosphodiester bonds results in phosphotriester formation (5 ) and bifunctional agents often react with two nucleophilic centers, producing inter- and intrastrand crosslinks (6 ).
