Development of a Leukæmia resistant to Cyclophosphamide (‘Cytoxan’)


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Arnold, H., and Bourseaux, F., Angew. Chemie, 70, 539 (1958).

    CAS  Article  Google Scholar 

  2. 2

    Brock, N., and Wilmanns, H., Deut. med. Wchnschr., 83, 453 (1958).

    CAS  Article  Google Scholar 

  3. 3

    Lane, M., and Kelly, M. G., Proc. Amer. Assoc. Cancer Res., 3, 35 (1959).

    Google Scholar 

  4. 4

    Arnold, H., Bourseaux, F., and Brock, N., Naturwiss., 45, 64 (1958). Burchenal, J. H., Oettgen, H. F., Reppert, J. A., and Coley, V., Proc. Amer. Assoc. Cancer Res., 3, 99 (1960). Foley, G. E., Friedman, O. M., and Drolet, B. P., ibid, 3, 111 (1960). Wight, K., Burk, D., Woods, M., and Lane, M., ibid., 3, 162 (1960).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Holzer, H., and Kröger, H., Klin. Wchnschr., 36, 677 (1958).

    CAS  Article  Google Scholar 

  6. 6

    Lane, M., Fed. Proc., 18, 413 (1959).

    Google Scholar 

  7. 7

    Lane, M., J. Nat. Cancer Inst., 23, 1347 (1959).

    CAS  PubMed  Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

LANE, M., YANCEY, S. Development of a Leukæmia resistant to Cyclophosphamide (‘Cytoxan’). Nature 188, 756–757 (1960).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.