Alkylating agent action

The alkylating agents are CCNS drugs. They form reactive molecular species that alkylate nucleophilic groups on DNA bases, particularly the N-7 position of guanine. This leads to crosslinking of bases, abnormal base-pairing, and DNA strand breakage. Tumor cell resistance to the drugs occurs through increased DNA repair, decreased drug permeability, and the production of trapping agents such as thiols. Alkylating agents exert their cytotoxic effects by covalently binding to nucleophilic groups on various cell constituents. Alkylation of DNA is probably the crucial cytotoxic reaction that is lethal to the tumor cells. Alkylating agents do not discriminate between cycling and resting cells, but they are most toxic for rapidly dividing cells. They are used in combination with other agents to treat a wide variety of lymphatic and solid cancers. In addition to being cytotoxic, all are mutagenic and carcinogenic and can lead to secondary malignancies such as acute leukemia.