Alkylating Agents

Alkylating agents (nitrogen mustards and ethy-eneimines) act by transferring alkyl groups to DNA in the N-7 position of guanine during cell division. There follows either DNA strand breakage or crosslinking of the two strands so that normal synthesis is prevented.

Examples include: busulfan, carmustine, chlorambucil, cyclophosphamide, ifosfamide, lomus-tine, melphalan, mustine (mechlorethamine), thio-tepa, treosulfan.

Systemic adverse effects of alkylating agents include nausea and vomiting, and bone marrow depression (delayed with carmustine and lomustine), cystitis6 (cyclophosphamide, ifosfamide) and pulmonary fibrosis (especially busulfan). Male infertility and premature menopause may occur. Myelodysplasia and secondary neoplasia are particularly associated with alkylator therapy (due to sublethal damage to normal cells) especially when accompanied by radiotherapy. These agents are used widely in the treatment of both haemato-logical and nonhaematological cancers, with varying degrees of success.

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