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Cyclophosphamide is an alkylating agent used in oncology and immunosuppression. It is metabolized to active forms that chemically modify DNA, primarily by attaching alkyl groups to guanine bases, resulting in monoadducts and the formation of DNA crosslinks (both interstrand and intrastrand). These changes disrupt DNA replication and transcription, inducing cell death, particularly in rapidly dividing cells. The DNA damage provides the basis for cyclophosphamide’s efficacy against cancer and immune disease, but also causes adverse effects such as mutagenesis, secondary cancers, infertility, and hemorrhagic cystitis.
Alkylation of DNA bases at the N-7 position of guanine; Formation of DNA crosslinks (interstrand and intrastrand); Irreversible DNA damage, blocking replication and transcription, ultimately leading to cell death
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