<unk> s <unk> s) form cyclic aminium ions (aziridinium rings) by intramolecular displacement of the chloride by the amine<unk> . This aziridinium group then alkylates DNA once it is attacked by the N-7 nucleophilic center on the guanine base. A second attack after the displacement of the second chlorine forms the second alkylation step that results in the formation of interstrand cross-links (ICLs) as it was shown in the early 1960s. At that time it was proposed that the ICLs were formed between N-7 atom of guanine residue in a 5’-d(GC) sequence. Later it was clearly demonstrated that<unk> s form a 1,3 ICL in the 5’-d(GNC) sequence. The strong cytotoxic effect caused by the formation of ICLs is what makes<unk> s an effective chemotherapeutic agent. Other compounds used in cancer chemotherapy that have the ability to form ICLs are cisplatin, mitomycin C, carmustine, and psoralen. These kinds of lesions are effective at forcing the cell to undergo apoptosis via p53, a protein which scans the genome for defects. Note that the alkylating damage itself is not cytotoxic and does not directly cause cell death.
Nitrogen mustard
Bleomycin
Lindane
Endosulfan
Diethylcarbamazine
Carbon tetrachloride
Dibenzofuran
Indeloxazine