The biology of alkylating-agent cellular injury.

Alkylating agents, such as nitrogen mustard, cyclophosphamide, and the nitrosoureas, have been used to treat many malignancies for more than 30 years. It is now clear that they are not only cytotoxic but also mutagenic and carcinogenic. The initial alkylation event, monoadduct formation on ring nitrogens or extra-cyclic oxygens of nucleotide bases, can result in chromosomal loss or single base mutation, both of which can lead to malignant transformation. The bone marrow is particularly sensitive to these events, and acute myelogenous leukemia is the most common malignancy caused by alkylating agents. Mechanisms of genetic damage and mutagenesis are discussed.