THE alkylating agent, N,N-bis-(β-chlorethyl)-N′, O-propylenephosphoric acid ester diamide1 (B-518, cyclophosphamide, ‘Endoxan’, ‘Cytoxan’), has been markedly effective in suppressing the growth of a variety of transplanted tumours in rats2,3 and mice3. The mechanism of activation of this agent has not been determined. It is known that the drug is not cytotoxic in vitro, but is activated in vivo 4. Nicotinamide has been reported to prevent the toxic and antitumour effects of ‘Cytoxan’5. However, the relationship of nicotinamide or diphosphopyridine nucleotide to either the activation or the action of this alkylating agent is unknown. Resistant tumours have proved valuable for the study of the mechanism of action of chemotherapeutic compounds. Sublines resistant to alkylating agents and derived from previously sensitive tumours are uncommon and have not been investigated extensively. It was thought that if a tumour resistant to ‘Cytoxan’ could be developed, it might provide a useful model for the study of the action of this alkylating agent.
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LANE, M., YANCEY, S. Development of a Leukæmia resistant to Cyclophosphamide (‘Cytoxan’). Nature 188, 756–757 (1960). https://doi.org/10.1038/188756a0
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