Reactions of nitrogen mustards with DNA.

This paper summarizes the mechanism of action and the covalent modifications of nucleic acids, nucleotides and nucleosides by nitrogen mustards. Nitrogen mustards react preferentially with guanine N7 in DNA in vitro. A few minor adducts have been characterized. Cross-links of nitrogen mustard and metabolites of cyclophosphamide that have been identified are diguanyl derivatives linked at N7. It is essential that studies of alkylation products in vivo be carried out, since characterization of alkylation products of cytostatic drugs should provide further insight into the mechanisms of cytotoxicity and, consequently, facilitate the development of more efficient anticancer agents. Furthermore, the monitoring of DNA adducts of therapeutic significance in patients may provide new avenues for the individualization of cancer therapy.