Mechanism of Action
The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. This metabolite is only formed in cells that have low levels of ALDH.
Phosphoramide mustard forms DNA crosslinks both between and within DNA strands at guanine N-7 positions (known as interstrand and intrastrand crosslinkages, respectively). This is irreversible and leads to cell death.
Cyclophosphamide has relatively little typical chemotherapy toxicity as ALDHs are present in relatively large concentrations in bone marrow stem cells, liver and intestinal epithelium. ALDHs protect these actively proliferating tissues against toxic effects of phosphoramide mustard and acrolein by converting aldophosphamide to carboxyphosphamide that does not give rise to the toxic metabolites phosphoramide mustard and acrolein.
Read more about this topic: Cyclophosphamide
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